Medical and Population Genetics | Leaders in Pharmaceutical Business Intelligence Group, LLC, Doing Business As LPBI Group, Newton, MA

Archive for the ‘Medical and Population Genetics’ Category

Summary – Volume 4, Part 2: Translational Medicine in Cardiovascular Diseases

Posted in Acute Myocardial Infarction, Advanced Drug Manufacturing Technology, Atherogenic Processes & Pathology, Autologous Cell Therapy, Automated Cell Processing, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Bone marrow derived cells, Ca2+ triggered activation, Ca2+ triggered activation, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Circulating Progenitor Cells, Coagulation Therapy and Internal Bleeding, Competition in regenerative stem cell science, Congenital Heart Disease, Cytoskeleton, Diabetes Mellitus, Discovery process, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Drug Toxicity, Electrophysiology, Endothelial cells, Epigenetics and Cardiovascular Risks, Experimental validation, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Health Economics and Outcomes Research, HTN, Human Immune System in Health and in Disease, Human neural progenitor cells, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, Medical and Population Genetics, Medical Devices R&D and Inventions, Metabolomics, Mitral Valve: Repair and Replacement, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Nitric Oxide in Health and Disease, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, PCI, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, PKC, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Pre-Clinical Animal Model Development, Proteomics, Regenerative Biology and Medicine, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Signaling, Skeletal muscle regeneration, Stem Cells for Regenerative Medicine, Stents & Tools, Technology Advance Assessment of, Theoretic convergence, Umbilical cord cells, Valves & Tools, tagged Apolipoprotein A1, Cardiovascular disease, Clinical trial, Coronary artery disease, diffusion distance, DNA Sequencing, embedded cells on synthetic matrix, endothelial cell, fibrous elongated cell, gene expression, genetics, genomics, glycerophospholipids, Heart disease, Heart Failure, Highly Sensitive Cardiac Troponin-T, homocysteine, hyperhomocysteinemia, Hypertension, imaging based screening, interstitial inflammation, Lipids, methionine, myocardial infarction, nitric oxide, Nitric oxide synthase, Personalized medicine, pharmaco-elution, Proteolysis, regenerative medicine, required amino acids, RNA, S-adenosylmethionine, Stem cell on May 10, 2014| Leave a Comment »

Summary – Volume 4, Part 2: Translational Medicine in Cardiovascular Diseases

Author and Curator: Larry H Bernstein, MD, FCAP

We have covered a large amount of material that involves

the development,
application, and
validation of outcomes of medical and surgical procedures

that are based on translation of science from the laboratory to the bedside, improving the standards of medical practice at an accelerated pace in the last quarter century, and in the last decade. Encouraging enabling developments have been:

1. The establishment of national and international outcomes databases for procedures by specialist medical societies

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

On Devices and On Algorithms: Prediction of Arrhythmia after Cardiac Surgery and ECG Prediction of an Onset of Paroxysmal Atrial Fibrillation
Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC
http://pharmaceuticalintelligence.com/2013/05/07/on-devices-and-on-algorithms-arrhythmia-after-cardiac-surgery-prediction-and-ecg-prediction-of-paroxysmal-atrial-fibrillation-onset/

Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?
Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/11/04/mitral-valve-repair-who-is-a-candidate-for-a-non-ablative-fully-non-invasive-procedure/

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions
Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

Survivals Comparison of Coronary Artery Bypass Graft (CABG) and Percutaneous Coronary Intervention (PCI) /Coronary Angioplasty
Larry H. Bernstein, MD, Writer And Aviva Lev-Ari, PhD, RN, Curator
http://pharmaceuticalintelligence.com/2013/06/23/comparison-of-cardiothoracic-bypass-and-percutaneous-interventional-catheterization-survivals/

Revascularization: PCI, Prior History of PCI vs CABG
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/04/25/revascularization-pci-prior-history-of-pci-vs-cabg/

Outcomes in High Cardiovascular Risk Patients: Prasugrel (Effient) vs. Clopidogrel (Plavix); Aliskiren (Tekturna) added to ACE or added to ARB
Reporter and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2012/08/27/outcomes-in-high-cardiovascular-risk-patients-prasugrel-effient-vs-clopidogrel-plavix-aliskiren-tekturna-added-to-ace-or-added-to-arb/

Endovascular Lower-extremity Revascularization Effectiveness: Vascular Surgeons (VSs), Interventional Cardiologists (ICs) and Interventional Radiologists (IRs)
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2012/08/13/coronary-artery-disease-medical-devices-solutions-from-first-in-man-stent-implantation-via-medical-ethical-dilemmas-to-drug-eluting-stents/

and more

2. The identification of problem areas, particularly in activation of the prothrombotic pathways, infection control to an extent, and targeting of pathways leading to progression or to arrythmogenic complications.

Cardiovascular Complications: Death from Reoperative Sternotomy after prior CABG, MVR, AVR, or Radiation; Complications of PCI; Sepsis from Cardiovascular Interventions Author, Introduction and Summary: Justin D Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/07/23/cardiovascular-complications-of-multiple-etiologies-repeat-sternotomy-post-cabg-or-avr-post-pci-pad-endoscopy-andor-resultant-of-systemic-sepsis/

Anticoagulation genotype guided dosing
Larry H. Bernstein, MD, FCAP, Author and Curator
http://pharmaceuticalintelligence.com/2013/12/08/anticoagulation-genotype-guided-dosing/

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

The Effects of Aprotinin on Endothelial Cell Coagulant Biology
Co-Author (Kamran Baig, MBBS, James Jaggers, MD, Jeffrey H. Lawson, MD, PhD) and Curator
http://pharmaceuticalintelligence.com/2013/07/20/the-effects-of-aprotinin-on-endothelial-cell-coagulant-biology/

Outcomes in High Cardiovascular Risk Patients: Prasugrel (Effient) vs. Clopidogrel (Plavix); Aliskiren (Tekturna) added to ACE or added to ARB
Reporter and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2012/08/27/outcomes-in-high-cardiovascular-risk-patients-prasugrel-effient-vs-clopidogrel-plavix-aliskiren-tekturna-added-to-ace-or-added-to-arb/

Pharmacogenomics – A New Method for Druggability Author and Curator: Demet Sag, PhD
http://pharmaceuticalintelligence.com/2014/04/28/pharmacogenomics-a-new-method-for-druggability/

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage Author: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-Sepsis-and-the-Cardiovascular-System-at-its-End-Stage/

3. Development of procedures that use a safer materials in vascular management.

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

Vascular Repair: Stents and Biologically Active Implants
Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, RN, PhD
http://pharmaceuticalintelligence.com/2013/05/04/stents-biologically-active-implants-and-vascular-repair/

Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES
Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN
http://PharmaceuticalIntelligence.com/2013/04/25/Contributions -to-vascular-biology/

MedTech & Medical Devices for Cardiovascular Repair – Curations by Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/04/17/medtech-medical-devices-for-cardiovascular-repair-curation-by-aviva-lev-ari-phd-rn/

4. Discrimination of cases presenting for treatment based on qualifications for medical versus surgical intervention.

Treatment Options for Left Ventricular Failure – Temporary Circulatory Support: Intra-aortic balloon pump (IABP) – Impella Recover LD/LP 5.0 and 2.5, Pump Catheters (Non-surgical) vs Bridge Therapy: Percutaneous Left Ventricular Assist Devices (pLVADs) and LVADs (Surgical)
Author: Larry H Bernstein, MD, FCAP And Curator: Justin D Pearlman, MD, PhD, FACC
http://pharmaceuticalintelligence.com/2013/07/17/treatment-options-for-left-ventricular-failure-temporary-circulatory-support-intra-aortic-balloon-pump-iabp-impella-recover-ldlp-5-0-and-2-5-pump-catheters-non-surgical-vs-bridge-therapy/

Coronary Reperfusion Therapies: CABG vs PCI – Mayo Clinic preprocedure Risk Score (MCRS) for Prediction of in-Hospital Mortality after CABG or PCI
Writer and Curator: Larry H. Bernstein, MD, FCAP and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/06/30/mayo-risk-score-for-percutaneous-coronary-intervention/

ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery Reporter: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/11/05/accaha-guidelines-for-coronary-artery-bypass-graft-surgery/

Mitral Valve Repair: Who is a Patient Candidate for a Non-Ablative Fully Non-Invasive Procedure?
Author, and Content Consultant to e-SERIES A: Cardiovascular Diseases: Justin Pearlman, MD, PhD, FACC and Article Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/11/04/mitral-valve-repair-who-is-a-candidate-for-a-non-ablative-fully-non-invasive-procedure/

5. This has become possible because of the advances in our knowledge of key related pathogenetic mechanisms involving gene expression and cellular regulation of complex mechanisms.

What is the key method to harness Inflammation to close the doors for many complex diseases?
Author and Curator: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/03/21/what-is-the-key-method-to-harness-inflammation-to-close-the-doors-for-many-complex-diseases/

CVD Prevention and Evaluation of Cardiovascular Imaging Modalities: Coronary Calcium Score by CT Scan Screening to justify or not the Use of Statin
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/03/03/cvd-prevention-and-evaluation-of-cardiovascular-imaging-modalities-coronary-calcium-score-by-ct-scan-screening-to-justify-or-not-the-use-of-statin/

Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/03/03/richard-lifton-md-phd-of-yale-university-and-howard-hughes-medical-institute-recipient-of-2014-breakthrough-prizes-awarded-in-life-sciences-for-the-discovery-of-genes-and-biochemical-mechanisms-tha/

Pathophysiological Effects of Diabetes on Ischemic-Cardiovascular Disease and on Chronic Obstructive Pulmonary Disease (COPD)
Curator: Larry H. Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/01/15/pathophysiological-effects-of-diabetes-on-ischemic-cardiovascular-disease-and-on-chronic-obstructive-pulmonary-disease-copd/

Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))
Reviewer and Co-Curator: Larry H Bernstein, MD, CAP and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/12/21/genetic-polymorphisms-of-ion-channels-have-a-role-in-the-pathogenesis-of-coronary-microvascular-dysfunction-and-ischemic-heart-disease/

Notable Contributions to Regenerative Cardiology Author and Curator: Larry H Bernstein, MD, FCAP and Article Commissioner: Aviva Lev-Ari, PhD, RD
http://pharmaceuticalintelligence.com/2013/10/20/notable-contributions-to-regenerative-cardiology/

As noted in the introduction, any of the material can be found and reviewed by content, and the eTOC is identified in attached:

http://wp.me/p2xfv8-1W

This completes what has been presented in Part 2, Vol 4 , and supporting references for the main points that are found in the Leaders in Pharmaceutical Intelligence Cardiovascular book. Part 1 was concerned with Posttranslational Modification of Proteins, vital for understanding cellular regulation and dysregulation. Part 2 was concerned with Translational Medical Therapeutics, the efficacy of medical and surgical decisions based on bringing the knowledge gained from the laboratory, and from clinical trials into the realm opf best practice. The time for this to occur in practice in the past has been through roughly a generation of physicians. That was in part related to the busy workload of physicians, and inability to easily access specialty literature as the volume and complexity increased. This had an effect of making access of a family to a primary care provider through a lifetime less likely than the period post WWII into the 1980s.

However, the growth of knowledge has accelerated in the specialties since the 1980’s so that the use of physician referral in time became a concern about the cost of medical care. This is not the place for or a matter for discussion here. It is also true that the scientific advances and improvements in available technology have had a great impact on medical outcomes. The only unrelated issue is that of healthcare delivery, which is not up to the standard set by serial advances in therapeutics, accompanied by high cost due to development costs, marketing costs, and development of drug resistance.

I shall identify continuing developments in cardiovascular diagnostics, therapeutics, and bioengineering that is and has been emerging.

1. Mechanisms of disease

REPORT: Mapping the Cellular Response to Small Molecules Using Chemogenomic Fitness Signatures

Science 11 April 2014:
Vol. 344 no. 6180 pp. 208-211
http://dx.doi.org/10.1126/science.1250217

Abstract: Genome-wide characterization of the in vivo cellular response to perturbation is fundamental to understanding how cells survive stress. Identifying the proteins and pathways perturbed by small molecules affects biology and medicine by revealing the mechanisms of drug action. We used a yeast chemogenomics platform that quantifies the requirement for each gene for resistance to a compound in vivo to profile 3250 small molecules in a systematic and unbiased manner. We identified 317 compounds that specifically perturb the function of 121 genes and characterized the mechanism of specific compounds. Global analysis revealed that the cellular response to small molecules is limited and described by a network of 45 major chemogenomic signatures. Our results provide a resource for the discovery of functional interactions among genes, chemicals, and biological processes.

Yeasty HIPHOP

Laura Zahn
Sci. Signal. 15 April 2014; 7(321): ec103. http://dx.doi.org/10.1126/scisignal.2005362

In order to identify how chemical compounds target genes and affect the physiology of the cell, tests of the perturbations that occur when treated with a range of pharmacological chemicals are required. By examining the haploinsufficiency profiling (HIP) and homozygous profiling (HOP) chemogenomic platforms, Lee et al.(p. 208) analyzed the response of yeast to thousands of different small molecules, with genetic, proteomic, and bioinformatic analyses. Over 300 compounds were identified that targeted 121 genes within 45 cellular response signature networks. These networks were used to extrapolate the likely effects of related chemicals, their impact upon genetic pathways, and to identify putative gene functions

Key Heart Failure Culprit Discovered

A team of cardiovascular researchers from the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai, Sanford-Burnham Medical Research Institute, and University of California, San Diego have identified a small, but powerful, new player in thIe onset and progression of heart failure. Their findings, published in the journal Nature on March 12, also show how they successfully blocked the newly discovered culprit.
Investigators identified a tiny piece of RNA called miR-25 that blocks a gene known as SERCA2a, which regulates the flow of calcium within heart muscle cells. Decreased SERCA2a activity is one of the main causes of poor contraction of the heart and enlargement of heart muscle cells leading to heart failure.

Using a functional screening system developed by researchers at Sanford-Burnham, the research team discovered miR-25 acts pathologically in patients suffering from heart failure, delaying proper calcium uptake in heart muscle cells. According to co-lead study authors Christine Wahlquist and Dr. Agustin Rojas Muñoz, developers of the approach and researchers in Mercola’s lab at Sanford-Burnham, they used high-throughput robotics to sift through the entire genome for microRNAs involved in heart muscle dysfunction.

Subsequently, the researchers at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai found that injecting a small piece of RNA to inhibit the effects of miR-25 dramatically halted heart failure progression in mice. In addition, it also improved their cardiac function and survival.

“In this study, we have not only identified one of the key cellular processes leading to heart failure, but have also demonstrated the therapeutic potential of blocking this process,” says co-lead study author Dr. Dongtak Jeong, a post-doctoral fellow at the Cardiovascular Research Center at Icahn School of Medicine at Mount Sinai in the laboratory of the study’s co-senior author Dr. Roger J. Hajjar.

Publication: Inhibition of miR-25 improves cardiac contractility in the failing heart.Christine Wahlquist, Dongtak Jeong, Agustin Rojas-Muñoz, Changwon Kho, Ahyoung Lee, Shinichi Mitsuyama, Alain Van Mil, Woo Jin Park, Joost P. G. Sluijter, Pieter A. F. Doevendans, Roger J. : Hajjar & Mark Mercola. Nature (March 2014) http://www.nature.com/nature/journal/vaop/ncurrent/full/nature13073.html

“Junk” DNA Tied to Heart Failure

Deep RNA Sequencing Reveals Dynamic Regulation of Myocardial Noncoding RNAs in Failing Human Heart and Remodeling With Mechanical Circulatory Support

Yang KC, Yamada KA, Patel AY, Topkara VK, George I, et al.
Circulation 2014; 129(9):1009-21.
http://dx.doi.org/10.1161/CIRCULATIONAHA.113.003863 http://circ.ahajournals.org/…/CIRCULATIONAHA.113.003863.full

The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support. These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.

Junk DNA was long thought to have no important role in heredity or disease because it doesn’t code for proteins. But emerging research in recent years has revealed that many of these sections of the genome produce noncoding RNA molecules that still have important functions in the body. They come in a variety of forms, some more widely studied than others. Of these, about 90% are called long noncoding RNAs (lncRNAs), and exploration of their roles in health and disease is just beginning.

The Washington University group performed a comprehensive analysis of all RNA molecules expressed in the human heart. The researchers studied nonfailing hearts and failing hearts before and after patients received pump support from left ventricular assist devices (LVAD). The LVADs increased each heart’s pumping capacity while patients waited for heart transplants.

In their study, the researchers found that unlike other RNA molecules, expression patterns of long noncoding RNAs could distinguish between two major types of heart failure and between failing hearts before and after they received LVAD support.

“The myocardial transcriptome is dynamically regulated in advanced heart failure and after LVAD support. The expression profiles of lncRNAs, but not mRNAs or miRNAs, can discriminate failing hearts of different pathologies and are markedly altered in response to LVAD support,” wrote the researchers. “These results suggest an important role for lncRNAs in the pathogenesis of heart failure and in reverse remodeling observed with mechanical support.”

‘Junk’ Genome Regions Linked to Heart Failure

In a recent issue of the journal Circulation, Washington University investigators report results from the first comprehensive analysis of all RNA molecules expressed in the human heart. The researchers studied nonfailing hearts and failing hearts before and after patients received pump support from left ventricular assist devices (LVAD). The LVADs increased each heart’s pumping capacity while patients waited for heart transplants.

“We took an unbiased approach to investigating which types of RNA might be linked to heart failure,” said senior author Jeanne Nerbonne, the Alumni Endowed Professor of Molecular Biology and Pharmacology. “We were surprised to find that long noncoding RNAs stood out.

In the new study, the investigators found that unlike other RNA molecules, expression patterns of long noncoding RNAs could distinguish between two major types of heart failure and between failing hearts before and after they received LVAD support.

“We don’t know whether these changes in long noncoding RNAs are a cause or an effect of heart failure,” Nerbonne said. “But it seems likely they play some role in coordinating the regulation of multiple genes involved in heart function.”

Nerbonne pointed out that all types of RNA molecules they examined could make the obvious distinction: telling the difference between failing and nonfailing hearts. But only expression of the long noncoding RNAs was measurably different between heart failure associated with a heart attack (ischemic) and heart failure without the obvious trigger of blocked arteries (nonischemic). Similarly, only long noncoding RNAs significantly changed expression patterns after implantation of left ventricular assist devices.

Comment

Decoding the noncoding transcripts in human heart failure

Xiao XG, Touma M, Wang Y
Circulation. 2014; 129(9): 958–960, http://dx.doi.org/10.1161/CIRCULATIONAHA.114.007548

Heart failure is a complex disease with a broad spectrum of pathological features. Despite significant advancement in clinical diagnosis through improved imaging modalities and hemodynamic approaches, reliable molecular signatures for better differential diagnosis and better monitoring of heart failure progression remain elusive. The few known clinical biomarkers for heart failure, such as plasma brain natriuretic peptide and troponin, have been shown to have limited use in defining the cause or prognosis of the disease.^1,2 Consequently, current clinical identification and classification of heart failure remain descriptive, mostly based on functional and morphological parameters. Therefore, defining the pathogenic mechanisms for hypertrophic versus dilated or ischemic versus nonischemic cardiomyopathies in the failing heart remain a major challenge to both basic science and clinic researchers. In recent years, mechanical circulatory support using left ventricular assist devices (LVADs) has assumed a growing role in the care of patients with end-stage heart failure.³ During the earlier years of LVAD application as a bridge to transplant, it became evident that some patients exhibit substantial recovery of ventricular function, structure, and electric properties.⁴ This led to the recognition that reverse remodeling is potentially an achievable therapeutic goal using LVADs. However, the underlying mechanism for the reverse remodeling in the LVAD-treated hearts is unclear, and its discovery would likely hold great promise to halt or even reverse the progression of heart failure.

Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation: A RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) Trial Analysis

Circulation. 2014; 129: 951-952 http://dx.doi.org/10.1161/CIR.0000000000000022

In patients with atrial fibrillation, impaired renal function is associated with a higher risk of thromboembolic events and major bleeding. Oral anticoagulation with vitamin K antagonists reduces thromboembolic events but raises the risk of bleeding. The new oral anticoagulant dabigatran has 80% renal elimination, and its efficacy and safety might, therefore, be related to renal function. In this prespecified analysis from the Randomized Evaluation of Long-Term Anticoagulant Therapy (RELY) trial, outcomes with dabigatran versus warfarin were evaluated in relation to 4 estimates of renal function, that is, equations based on creatinine levels (Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]) and cystatin C. The rates of stroke or systemic embolism were lower with dabigatran 150 mg and similar with 110 mg twice daily irrespective of renal function. Rates of major bleeding were lower with dabigatran 110 mg and similar with 150 mg twice daily across the entire range of renal function. However, when the CKD-EPI or MDRD equations were used, there was a significantly greater relative reduction in major bleeding with both doses of dabigatran than with warfarin in patients with estimated glomerular filtration rate ≥80 mL/min. These findings show that dabigatran can be used with the same efficacy and adequate safety in patients with a wide range of renal function and that a more accurate estimate of renal function might be useful for improved tailoring of anticoagulant treatment in patients with atrial fibrillation and an increased risk of stroke.

Aldosterone Regulates MicroRNAs in the Cortical Collecting Duct to Alter Sodium Transport.

Robert S Edinger, Claudia Coronnello, Andrew J Bodnar, William A Laframboise, Panayiotis V Benos, Jacqueline Ho, John P Johnson, Michael B Butterworth

Journal of the American Society of Nephrology (Impact Factor: 8.99). 04/2014; http://dx. DO.org/I:10.1681/ASN.2013090931

Source: PubMed

ABSTRACT A role for microRNAs (miRs) in the physiologic regulation of sodium transport in the kidney has not been established. In this study, we investigated the potential of aldosterone to alter miR expression in mouse cortical collecting duct (mCCD) epithelial cells. Microarray studies demonstrated the regulation of miR expression by aldosterone in both cultured mCCD and isolated primary distal nephron principal cells.

Aldosterone regulation of the most significantly downregulated miRs, mmu-miR-335-3p, mmu-miR-290-5p, and mmu-miR-1983 was confirmed by quantitative RT-PCR. Reducing the expression of these miRs separately or in combination increased epithelial sodium channel (ENaC)-mediated sodium transport in mCCD cells, without mineralocorticoid supplementation. Artificially increasing the expression of these miRs by transfection with plasmid precursors or miR mimic constructs blunted aldosterone stimulation of ENaC transport.

Using a newly developed computational approach, termed ComiR, we predicted potential gene targets for the aldosterone-regulated miRs and confirmed ankyrin 3 (Ank3) as a novel aldosterone and miR-regulated protein.

A dual-luciferase assay demonstrated direct binding of the miRs with the Ank3-3′ untranslated region. Overexpression of Ank3 increased and depletion of Ank3 decreased ENaC-mediated sodium transport in mCCD cells. These findings implicate miRs as intermediaries in aldosterone signaling in principal cells of the distal kidney nephron.

2. Diagnostic Biomarker Status

A prospective study of the impact of serial troponin measurements on the diagnosis of myocardial infarction and hospital and 6-month mortality in patients admitted to ICU with non-cardiac diagnoses.

Marlies Ostermann, Jessica Lo, Michael Toolan, Emma Tuddenham, Barnaby Sanderson, Katie Lei, John Smith, Anna Griffiths, Ian Webb, James Coutts, John hambers, Paul Collinson, Janet Peacock, David Bennett, David Treacher

Critical care (London, England) (Impact Factor: 4.72). 04/2014; 18(2):R62. http://dx.doi.org/:10.1186/cc13818

Source: PubMed

ABSTRACT Troponin T (cTnT) elevation is common in patients in the Intensive Care Unit (ICU) and associated with morbidity and mortality. Our aim was to determine the epidemiology of raised cTnT levels and contemporaneous electrocardiogram (ECG) changes suggesting myocardial infarction (MI) in ICU patients admitted for non-cardiac reasons.
cTnT and ECGs were recorded daily during week 1 and on alternate days during week 2 until discharge from ICU or death. ECGs were interpreted independently for the presence of ischaemic changes. Patients were classified into 4 groups: (i) definite MI (cTnT >=15 ng/L and contemporaneous changes of MI on ECG), (ii) possible MI (cTnT >=15 ng/L and contemporaneous ischaemic changes on ECG), (iii) troponin rise alone (cTnT >=15 ng/L), or (iv) normal. Medical notes were screened independently by two ICU clinicians for evidence that the clinical teams had considered a cardiac event.
Data from 144 patients were analysed [42% female; mean age 61.9 (SD 16.9)]. 121 patients (84%) had at least one cTnT level >=15 ng/L. A total of 20 patients (14%) had a definite MI, 27% had a possible MI, 43% had a cTNT rise without contemporaneous ECG changes, and 16% had no cTNT rise. ICU, hospital and 180 day mortality were significantly higher in patients with a definite or possible MI.Only 20% of definite MIs were recognised by the clinical team. There was no significant difference in mortality between recognised and non-recognised events.At time of cTNT rise, 100 patients (70%) were septic and 58% were on vasopressors. Patients who were septic when cTNT was elevated had an ICU mortality of 28% compared to 9% in patients without sepsis. ICU mortality of patients who were on vasopressors at time of cTNT elevation was 37% compared to 1.7% in patients not on vasopressors.
The majority of critically ill patients (84%) had a cTnT rise and 41% met criteria for a possible or definite MI of whom only 20% were recognised clinically. Mortality up to 180 days was higher in patients with a cTnT rise.

Prognostic performance of high-sensitivity cardiac troponin T kinetic changes adjusted for elevated admission values and the GRACE score in an unselected emergency department population.

Moritz Biener, Matthias Mueller, Mehrshad Vafaie, Allan S Jaffe, Hugo A Katus,Evangelos Giannitsis

Clinica chimica acta; international journal of clinical chemistry (Impact Factor: 2.54). 04/2014; http://dx.doi.org/10.1016/j.cca.2014.04.007

Source: PubMed

ABSTRACT To test the prognostic performance of rising and falling kinetic changes of high-sensitivity cardiac troponin T (hs-cTnT) and the GRACE score.
Rising and falling hs-cTnT changes in an unselected emergency department population were compared.
635 patients with a hs-cTnT >99th percentile admission value were enrolled. Of these, 572 patients qualified for evaluation with rising patterns (n=254, 44.4%), falling patterns (n=224, 39.2%), or falling patterns following an initial rise (n=94, 16.4%). During 407days of follow-up, we observed 74 deaths, 17 recurrent AMI, and 79 subjects with a composite of death/AMI. Admission values >14ng/L were associated with a higher rate of adverse outcomes (OR, 95%CI:death:12.6, 1.8-92.1, p=0.01, death/AMI:6.7, 1.6-27.9, p=0.01). Neither rising nor falling changes increased the AUC of baseline values (AUC: rising 0.562 vs 0.561, p=ns, falling: 0.533 vs 0.575, p=ns). A GRACE score ≥140 points indicated a higher risk of death (OR, 95%CI: 3.14, 1.84-5.36), AMI (OR,95%CI: 1.56, 0.59-4.17), or death/AMI (OR, 95%CI: 2.49, 1.51-4.11). Hs-cTnT changes did not improve prognostic performance of a GRACE score ≥140 points (AUC, 95%CI: death: 0.635, 0.570-0.701 vs. 0.560, 0.470-0.649 p=ns, AMI: 0.555, 0.418-0.693 vs. 0.603, 0.424-0.782, p=ns, death/AMI: 0.610, 0.545-0.676 vs. 0.538, 0.454-0.622, p=ns). Coronary angiography was performed earlier in patients with rising than with falling kinetics (median, IQR [hours]:13.7, 5.5-28.0 vs. 20.8, 6.3-59.0, p=0.01).
Neither rising nor falling hs-cTnT changes improve prognostic performance of elevated hs-cTnT admission values or the GRACE score. However, rising values are more likely associated with the decision for earlier invasive strategy.

Troponin assays for the diagnosis of myocardial infarction and acute coronary syndrome: where do we stand?

Arie Eisenman

ABSTRACT: Under normal circumstances, most intracellular troponin is part of the muscle contractile apparatus, and only a small percentage (< 2-8%) is free in the cytoplasm. The presence of a cardiac-specific troponin in the circulation at levels above normal is good evidence of damage to cardiac muscle cells, such as myocardial infarction, myocarditis, trauma, unstable angina, cardiac surgery or other cardiac procedures. Troponins are released as complexes leading to various cut-off values depending on the assay used. This makes them very sensitive and specific indicators of cardiac injury. As with other cardiac markers, observation of a rise and fall in troponin levels in the appropriate time-frame increases the diagnostic specificity for acute myocardial infarction. They start to rise approximately 4-6 h after the onset of acute myocardial infarction and peak at approximately 24 h, as is the case with creatine kinase-MB. They remain elevated for 7-10 days giving a longer diagnostic window than creatine kinase. Although the diagnosis of various types of acute coronary syndrome remains a clinical-based diagnosis, the use of troponin levels contributes to their classification. This Editorial elaborates on the nature of troponin, its classification, clinical use and importance, as well as comparing it with other currently available cardiac markers.

Expert Review of Cardiovascular Therapy 07/2006; 4(4):509-14. http://dx.doi.org/:10.1586/14779072.4.4.509

Impact of redefining acute myocardial infarction on incidence, management and reimbursement rate of acute coronary syndromes.

Carísi A Polanczyk, Samir Schneid, Betina V Imhof, Mariana Furtado, Carolina Pithan, Luis E Rohde, Jorge P Ribeiro

ABSTRACT: Although redefinition for acute myocardial infarction (AMI) has been proposed few years ago, to date it has not been universally adopted by many institutions. The purpose of this study is to evaluate the diagnostic, prognostic and economical impact of the new diagnostic criteria for AMI. Patients consecutively admitted to the emergency department with suspected acute coronary syndromes were enrolled in this study. Troponin T (cTnT) was measured in samples collected for routine CK-MB analyses and results were not available to physicians. Patients without AMI by traditional criteria and cTnT > or = 0.035 ng/mL were coded as redefined AMI. Clinical outcomes were hospital death, major cardiac events and revascularization procedures. In-hospital management and reimbursement rates were also analyzed. Among 363 patients, 59 (16%) patients had AMI by conventional criteria, whereas additional 75 (21%) had redefined AMI, an increase of 127% in the incidence. Patients with redefined AMI were significantly older, more frequently male, with atypical chest pain and more risk factors. In multivariate analysis, redefined AMI was associated with 3.1 fold higher hospital death (95% CI: 0.6-14) and a 5.6 fold more cardiac events (95% CI: 2.1-15) compared to those without AMI. From hospital perspective, based on DRGs payment system, adoption of AMI redefinition would increase 12% the reimbursement rate [3552 Int dollars per 100 patients evaluated]. The redefined criteria result in a substantial increase in AMI cases, and allow identification of high-risk patients. Efforts should be made to reinforce the adoption of AMI redefinition, which may result in more qualified and efficient management of ACS.

International Journal of Cardiology 03/2006; 107(2):180-7. · 5.51 Impact Factor http://www.sciencedirect.com/science/article/pii/S0167527305005279

3. Biomedical Engineerin3g

Safety and Efficacy of an Injectable Extracellular Matrix Hydrogel for Treating Myocardial Infarction

Sonya B. Seif-Naraghi, Jennifer M. Singelyn, Michael A. Salvatore, et al.
Sci Transl Med 20 February 2013 5:173ra25 http://dx.doi.org/10.1126/scitranslmed.3005503

Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of application with substantial intrinsic hurdles, but where human translation is now occurring.

Acellular Biomaterials: An Evolving Alternative to Cell-Based Therapies

J. A. Burdick, R. L. Mauck, J. H. Gorman, R. C. Gorman,
Sci. Transl. Med. 2013; 5, (176): 176 ps4 http://stm.sciencemag.org/content/5/176/176ps4

Acellular biomaterials can stimulate the local environment to repair tissues without the regulatory and scientific challenges of cell-based therapies. A greater understanding of the mechanisms of such endogenous tissue repair is furthering the design and application of these biomaterials. We discuss recent progress in acellular materials for tissue repair, using cartilage and cardiac tissues as examples of applications with substantial intrinsic hurdles, but where human translation is now occurring.

Instructive Nanofiber Scaffolds with VEGF Create a Microenvironment for Arteriogenesis and Cardiac Repair

Yi-Dong Lin, Chwan-Yau Luo, Yu-Ning Hu, Ming-Long Yeh, Ying-Chang Hsueh, Min-Yao Chang, et al.
Sci Transl Med 8 August 2012; 4(146):ra109. http://dx.doi.org/ 10.1126/scitranslmed.3003841

Angiogenic therapy is a promising approach for tissue repair and regeneration. However, recent clinical trials with protein delivery or gene therapy to promote angiogenesis have failed to provide therapeutic effects. A key factor for achieving effective revascularization is the durability of the microvasculature and the formation of new arterial vessels. Accordingly, we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats. Our data showed that when injected with NF, VEGF delivery was sustained within the myocardium for up to 14 days, and the side effects of systemic edema and proteinuria were significantly reduced to the same level as that of control. NF/VEGF injection significantly improved angiogenesis, arteriogenesis, and cardiac performance 28 days after myocardial infarction. NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats. In summary, this study demonstrates a new strategy for cardiovascular repair with potential for future clinical translation.

Manufacturing Challenges in Regenerative Medicine

I. Martin, P. J. Simmons, D. F. Williams.
Sci. Transl. Med. 2014; 6(232): fs16. http://dx.doi.org/10.1126/scitranslmed.3008558

Along with scientific and regulatory issues, the translation of cell and tissue therapies in the routine clinical practice needs to address standardization and cost-effectiveness through the definition of suitable manufacturing paradigms.

Read Full Post »

Summary of Translational Medicine – e-Series A: Cardiovascular Diseases, Volume Four – Part 1

Posted in Academic Publishing, Acute Myocardial Infarction, Advanced Drug Manufacturing Technology, Alzheimer's Disease, Atherogenic Processes & Pathology, Autologous Cell Therapy, Automated Cell Processing, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Bone Disease and Musculoskeletal Disease, Bone marrow derived cells, Ca2+ triggered activation, Ca2+ triggered activation, Cachexia, Calcium Signaling, Calmodulin, Calmodulin Kinase and Contraction, Cardiac & Vascular Repair Tools Subsegment, Cardiac and Cardiovascular Surgical Procedures, Cardiac muscle regeneration, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Circulating Progenitor Cells, Coagulation Therapy and Internal Bleeding, Competition in regenerative stem cell science, Computational Biology/Systems and Bioinformatics, Curation, Cytoskeleton, Diabetes Mellitus, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, Drug Toxicity, Electrophysiology, Endothelial cells, Epigenetics and Cardiovascular Risks, Etiology, Evolutionary cognition, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Expression, Health Economics and Outcomes Research, Human Immune System in Health and in Disease, International Global Work in Pharmaceutical, Interviews with Scientific Leaders, Medical and Population Genetics, Medical Device Therapies for Altzheimer’s Disease, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Na-K transport, Na-K-ATPase, Neurohumoral Transmission, Nitric Oxide in Health and Disease, Nutrition, Nutritional Supplements: Atherogenesis, lipid metabolism, Origins of Cardiovascular Disease, Oxidative phosphorylation, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmacologic toxicities, Pharmacotherapy of Cardiovascular Disease, Phosphorylation, PKC, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, Regenerative Biology and Medicine, S-nitrosylation, Signaling, Skeletal muscle regeneration, Statistical Methods for Research Evaluation, Stem Cells for Regenerative Medicine, Stents & Tools, Synaptic vesicle, Systemic Inflammatory Response Related Disorders, Technology Advance Assessment of, Translational Effectiveness, Translational Science, Ubiquitinylation, Water Transporters, tagged bioengineering, Cardiovascular Disorders, computational biology, Coronary artery disease, DNA Sequencing, functional proteomics, gene expression, gene silencing, genetic engineering, Heart Failure, Human Genome Project, Hypertension, MicroRNA, mtRNA, myocardial infarction, nitric oxide, Nitric oxide synthase, Personalized medicine, protein modifications, Proteomics, reverse engineering, RNA, signaling pathways, Stem cell, synbiology on April 28, 2014| Leave a Comment »

Summary of Translational Medicine – e-Series A: Cardiovascular Diseases, Volume Four – Part 1

Author and Curator: Larry H Bernstein, MD, FCAP

and

Curator: Aviva Lev-Ari, PhD, RN

Article ID #135: Summary of Translational Medicine – e-Series A: Cardiovascular Diseases, Volume Four – Part 1. Published on 4/28/2014

WordCloud Image Produced by Adam Tubman

Part 1 of Volume 4 in the e-series A: Cardiovascular Diseases and Translational Medicine, provides a foundation for grasping a rapidly developing surging scientific endeavor that is transcending laboratory hypothesis testing and providing guidelines to:

Target genomes and multiple nucleotide sequences involved in either coding or in regulation that might have an impact on complex diseases, not necessarily genetic in nature.
Target signaling pathways that are demonstrably maladjusted, activated or suppressed in many common and complex diseases, or in their progression.
Enable a reduction in failure due to toxicities in the later stages of clinical drug trials as a result of this science-based understanding.
Enable a reduction in complications from the improvement of machanical devices that have already had an impact on the practice of interventional procedures in cardiology, cardiac surgery, and radiological imaging, as well as improving laboratory diagnostics at the molecular level.
Enable the discovery of new drugs in the continuing emergence of drug resistance.
Enable the construction of critical pathways and better guidelines for patient management based on population outcomes data, that will be critically dependent on computational methods and large data-bases.

What has been presented can be essentially viewed in the following Table:

Summary Table for TM – Part 1

There are some developments that deserve additional development:

1. The importance of mitochondrial function in the activity state of the mitochondria in cellular work (combustion) is understood, and impairments of function are identified in diseases of muscle, cardiac contraction, nerve conduction, ion transport, water balance, and the cytoskeleton – beyond the disordered metabolism in cancer. A more detailed explanation of the energetics that was elucidated based on the electron transport chain might also be in order.

2. The processes that are enabling a more full application of technology to a host of problems in the environment we live in and in disease modification is growing rapidly, and will change the face of medicine and its allied health sciences.

Electron Transport and Bioenergetics

Deferred for metabolomics topic

Synthetic Biology

Introduction to Synthetic Biology and Metabolic Engineering

Kristala L. J. Prather: Part-1 <iBiology > iBioSeminars > Biophysics & Chemical Biology >

http://www.ibiology.org Lecturers generously donate their time to prepare these lectures. The project is funded by NSF and NIGMS, and is supported by the ASCB and HHMI.
Dr. Prather explains that synthetic biology involves applying engineering principles to biological systems to build “biological machines”.

Dr. Prather has received numerous awards both for her innovative research and for excellence in teaching. Learn more about how Kris became a scientist at

http://science360.gov/obj/video/753bb4fa-aafb-4315-848e-51066ed9799a/finding-way-kristala-l-jones-prather-phd

Prather 1: Synthetic Biology and Metabolic Engineering 2/6/14IntroductionLecture Overview In the first part of her lecture, Dr. Prather explains that synthetic biology involves applying engineering principles to biological systems to build “biological machines”. The key material in building these machines is synthetic DNA. Synthetic DNA can be added in different combinations to biological hosts, such as bacteria, turning them into chemical factories that can produce small molecules of choice. In Part 2, Prather describes how her lab used design principles to engineer E. coli that produce glucaric acid from glucose. Glucaric acid is not naturally produced in bacteria, so Prather and her colleagues “bioprospected” enzymes from other organisms and expressed them in E. coli to build the needed enzymatic pathway. Prather walks us through the many steps of optimizing the timing, localization and levels of enzyme expression to produce the greatest yield. Speaker Bio: Kristala Jones Prather received her S.B. degree from the Massachusetts Institute of Technology and her PhD at the University of California, Berkeley both in chemical engineering. Upon graduation, Prather joined the Merck Research Labs for 4 years before returning to academia. Prather is now an Associate Professor of Chemical Engineering at MIT and an investigator with the multi-university Synthetic Biology Engineering Reseach Center (SynBERC). Her lab designs and constructs novel synthetic pathways in microorganisms converting them into tiny factories for the production of small molecules. Dr. Prather has received numerous awards both for her innovative research and for excellence in teaching.

VIEW VIDEOS

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk#t=0

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk#t=12

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk#t=74

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk#t=129

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk#t=168

https://www.youtube.com/watch?feature=player_embedded&v=ndThuqVumAk

David Bartel: micro-RNAs

I. Introduction to microRNAs

https://www.youtube.com/watch?feature=player_embedded&v=dupzE66J8u4#t=0

– See more at: http://www.ibiology.org/ibioseminars/genetics-gene-regulation/david-bartel-part-1.html#sthash.nGGr1tIt.dpuf

II. Regulatory Effects of Mammalian microRNAs

https://www.youtube.com/watch?feature=player_embedded&v=TcZK_A_wcWQ#t=0

https://www.youtube.com/watch?feature=player_embedded&v=TcZK_A_wcWQ

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

in INTECH
Current Basic and Pathological Approaches to
the Function of Muscle Cells and Tissues – From Molecules to HumansLarissa Lipskaia, Isabelle Limon, Regis Bobe and Roger Hajjar
Additional information is available at the end of the chapter
http://dx.doi.org/10.5772/48240

1. Introduction
Calcium ions (Ca ) are present in low concentrations in the cytosol (~100 nM) and in high concentrations (in mM range) in both the extracellular medium and intracellular stores (mainly sarco/endo/plasmic reticulum, SR). This differential allows the calcium ion messenger that carries information
as diverse as contraction, metabolism, apoptosis, proliferation and/or hypertrophic growth. The mechanisms responsible for generating a Ca signal greatly differ from one cell type to another.

In the different types of vascular smooth muscle cells (VSMC), enormous variations do exist with regard to the mechanisms responsible for generating Ca signal. In each VSMC phenotype (synthetic/proliferating and contractile [1], tonic or phasic), the Ca signaling system is adapted to its particular function and is due to the specific patterns of expression and regulation of Ca.
For instance, in contractile VSMCs, the initiation of contractile events is driven by mem- brane depolarization; and the principal entry-point for extracellular Ca is the voltage-operated L-type calcium channel (LTCC). In contrast, in synthetic/proliferating VSMCs, the principal way-in for extracellular Ca is the store-operated calcium (SOC) channel.
Whatever the cell type, the calcium signal consists of limited elevations of cytosolic free calcium ions in time and space. The calcium pump, sarco/endoplasmic reticulum Ca ATPase (SERCA), has a critical role in determining the frequency of SR Ca release by upload into the sarcoplasmic
sensitivity of SR calcium channels, Ryanodin Receptor, RyR and Inositol tri-Phosphate Receptor, IP3R.
Synthetic VSMCs have a fibroblast appearance, proliferate readily, and synthesize increased levels of various extracellular matrix components, particularly fibronectin, collagen types I and III, and tropoelastin [1].
Contractile VSMCs have a muscle-like or spindle-shaped appearance and well-developed contractile apparatus resulting from the expression and intracellular accumulation of thick and thin muscle filaments [1].

Schematic representation of Calcium Cycling in Contractile and Proliferating VSMCs

Figure 1. Schematic representation of Calcium Cycling in Contractile and Proliferating VSMCs.

Left panel: schematic representation of calcium cycling in quiescent /contractile VSMCs. Contractile re-sponse is initiated by extracellular Ca influx due to activation of Receptor Operated Ca (through phosphoinositol-coupled receptor) or to activation of L-Type Calcium channels (through an increase in luminal pressure). Small increase of cytosolic due IP3 binding to IP3R (puff) or RyR activation by LTCC or ROC-dependent Ca influx leads to large SR Ca IP3R or RyR clusters (“Ca -induced Ca SR calcium pumps (both SERCA2a and SERCA2b are expressed in quiescent VSMCs), maintaining high concentration of cytosolic Ca and setting the sensitivity of RyR or IP3R for the next spike.
Contraction of VSMCs occurs during oscillatory Ca transient.
Middle panel: schematic representa tion of atherosclerotic vessel wall. Contractile VSMC are located in the media layer, synthetic VSMC are located in sub-endothelial intima.
Right panel: schematic representation of calcium cycling in quiescent /contractile VSMCs. Agonist binding to phosphoinositol-coupled receptor leads to the activation of IP3R resulting in large increase in cytosolic Ca calcium pumps (only SERCA2b, having low turnover and low affinity to Ca depletion leads to translocation of SR Ca sensor STIM1 towards PM, resulting in extracellular Ca influx though opening of Store Operated Channel (CRAC). Resulted steady state Ca transient is critical for activation of proliferation-related transcription factors ‘NFAT).
Abbreviations: PLC – phospholipase C; PM – plasma membrane; PP2B – Ca /calmodulin-activated protein phosphatase 2B (calcineurin); ROC- receptor activated channel; IP3 – inositol-1,4,5-trisphosphate, IP3R – inositol-1,4,5- trisphosphate receptor; RyR – ryanodine receptor; NFAT – nuclear factor of activated T-lymphocytes; VSMC – vascular smooth muscle cells; SERCA – sarco(endo)plasmic reticulum Ca sarcoplasmic reticulum.

Time for New DNA Synthesis and Sequencing Cost Curves

By Rob Carlson

I’ll start with the productivity plot, as this one isn’t new. For a discussion of the substantial performance increase in sequencing compared to Moore’s Law, as well as the difficulty of finding this data, please see this post. If nothing else, keep two features of the plot in mind: 1) the consistency of the pace of Moore’s Law and 2) the inconsistency and pace of sequencing productivity. Illumina appears to be the primary driver, and beneficiary, of improvements in productivity at the moment, especially if you are looking at share prices. It looks like the recently announced NextSeq and Hiseq instruments will provide substantially higher productivities (hand waving, I would say the next datum will come in another order of magnitude higher), but I think I need a bit more data before officially putting another point on the plot.

cost-of-oligo-and-gene-synthesis

Illumina’s instruments are now responsible for such a high percentage of sequencing output that the company is effectively setting prices for the entire industry. Illumina is being pushed by competition to increase performance, but this does not necessarily translate into lower prices. It doesn’t behoove Illumina to drop prices at this point, and we won’t see any substantial decrease until a serious competitor shows up and starts threatening Illumina’s market share. The absence of real competition is the primary reason sequencing prices have flattened out over the last couple of data points.

Note that the oligo prices above are for column-based synthesis, and that oligos synthesized on arrays are much less expensive. However, array synthesis comes with the usual caveat that the quality is generally lower, unless you are getting your DNA from Agilent, which probably means you are getting your dsDNA from Gen9.

Note also that the distinction between the price of oligos and the price of double-stranded sDNA is becoming less useful. Whether you are ordering from Life/Thermo or from your local academic facility, the cost of producing oligos is now, in most cases, independent of their length. That’s because the cost of capital (including rent, insurance, labor, etc) is now more significant than the cost of goods. Consequently, the price reflects the cost of capital rather than the cost of goods. Moreover, the cost of the columns, reagents, and shipping tubes is certainly more than the cost of the atoms in the sDNA you are ostensibly paying for. Once you get into longer oligos (substantially larger than 50-mers) this relationship breaks down and the sDNA is more expensive. But, at this point in time, most people aren’t going to use longer oligos to assemble genes unless they have a tricky job that doesn’t work using short oligos.

Looking forward, I suspect oligos aren’t going to get much cheaper unless someone sorts out how to either 1) replace the requisite human labor and thereby reduce the cost of capital, or 2) finally replace the phosphoramidite chemistry that the industry relies upon.

IDT’s gBlocks come at prices that are constant across quite substantial ranges in length. Moreover, part of the decrease in price for these products is embedded in the fact that you are buying smaller chunks of DNA that you then must assemble and integrate into your organism of choice.

Someone who has purchased and assembled an absolutely enormous amount of sDNA over the last decade, suggested that if prices fell by another order of magnitude, he could switch completely to outsourced assembly. This is a potentially interesting “tipping point”. However, what this person really needs is sDNA integrated in a particular way into a particular genome operating in a particular host. The integration and testing of the new genome in the host organism is where most of the cost is. Given the wide variety of emerging applications, and the growing array of hosts/chassis, it isn’t clear that any given technology or firm will be able to provide arbitrary synthetic sequences incorporated into arbitrary hosts.

TrackBack URL: http://www.synthesis.cc/cgi-bin/mt/mt-t.cgi/397

Startup to Strengthen Synthetic Biology and Regenerative Medicine Industries with Cutting Edge Cell Products

28 Nov 2013 | PR Web

Dr. Jon Rowley and Dr. Uplaksh Kumar, Co-Founders of RoosterBio, Inc., a newly formed biotech startup located in Frederick, are paving the way for even more innovation in the rapidly growing fields of Synthetic Biology and Regenerative Medicine. Synthetic Biology combines engineering principles with basic science to build biological products, including regenerative medicines and cellular therapies. Regenerative medicine is a broad definition for innovative medical therapies that will enable the body to repair, replace, restore and regenerate damaged or diseased cells, tissues and organs. Regenerative therapies that are in clinical trials today may enable repair of damaged heart muscle following heart attack, replacement of skin for burn victims, restoration of movement after spinal cord injury, regeneration of pancreatic tissue for insulin production in diabetics and provide new treatments for Parkinson’s and Alzheimer’s diseases, to name just a few applications.

While the potential of the field is promising, the pace of development has been slow. One main reason for this is that the living cells required for these therapies are cost-prohibitive and not supplied at volumes that support many research and product development efforts. RoosterBio will manufacture large quantities of standardized primary cells at high quality and low cost, which will quicken the pace of scientific discovery and translation to the clinic. “Our goal is to accelerate the development of products that incorporate living cells by providing abundant, affordable and high quality materials to researchers that are developing and commercializing these regenerative technologies” says Dr. Rowley

Life at the Speed of Light

http://kcpw.org/?powerpress_pinw=92027-podcast

NHMU Lecture featuring – J. Craig Venter, Ph.D.
Founder, Chairman, and CEO – J. Craig Venter Institute; Co-Founder and CEO, Synthetic Genomics Inc.

J. Craig Venter, Ph.D., is Founder, Chairman, and CEO of the J. Craig Venter Institute (JVCI), a not-for-profit, research organization dedicated to human, microbial, plant, synthetic and environmental research. He is also Co-Founder and CEO of Synthetic Genomics Inc. (SGI), a privately-held company dedicated to commercializing genomic-driven solutions to address global needs.

In 1998, Dr. Venter founded Celera Genomics to sequence the human genome using new tools and techniques he and his team developed. This research culminated with the February 2001 publication of the human genome in the journal, Science. Dr. Venter and his team at JVCI continue to blaze new trails in genomics. They have sequenced and a created a bacterial cell constructed with synthetic DNA, putting humankind at the threshold of a new phase of biological research. Whereas, we could previously read the genetic code (sequencing genomes), we can now write the genetic code for designing new species.

The science of synthetic genomics will have a profound impact on society, including new methods for chemical and energy production, human health and medical advances, clean water, and new food and nutritional products. One of the most prolific scientists of the 21st century for his numerous pioneering advances in genomics, he guides us through this emerging field, detailing its origins, current challenges, and the potential positive advances.

His work on synthetic biology truly embodies the theme of “pushing the boundaries of life.” Essentially, Venter is seeking to “write the software of life” to create microbes designed by humans rather than only through evolution. The potential benefits and risks of this new technology are enormous. It also requires us to examine, both scientifically and philosophically, the question of “What is life?”

J Craig Venter wants to digitize DNA and transmit the signal to teleport organisms

http://pharmaceuticalintelligence.com/2013/11/01/j-craig-venter-wants-to-digitize-dna-and-transmit-the-signal-to-teleport-organisms/

2013 Genomics: The Era Beyond the Sequencing of the Human Genome: Francis Collins, Craig Venter, Eric Lander, et al.

http://pharmaceuticalintelligence.com/2013/02/11/2013-genomics-the-era-beyond-the-sequencing-human-genome-francis-collins-craig-venter-eric-lander-et-al/

Human Longevity Inc (HLI) – $70M in Financing of Venter’s New Integrative Omics and Clinical Bioinformatics

http://pharmaceuticalintelligence.com/2014/03/05/human-longevity-inc-hli-70m-in-financing-of-venters-new-integrative-omics-and-clinical-bioinformatics/

Where Will the Century of Biology Lead Us?

By Randall Mayes

A technology trend analyst offers an overview of synthetic biology, its potential applications, obstacles to its development, and prospects for public approval.

In addition to boosting the economy, synthetic biology projects currently in development could have profound implications for the future of manufacturing, sustainability, and medicine.
Before society can fully reap the benefits of synthetic biology, however, the field requires development and faces a series of hurdles in the process. Do researchers have the scientific know-how and technical capabilities to develop the field?

Biology + Engineering = Synthetic Biology

Bioengineers aim to build synthetic biological systems using compatible standardized parts that behave predictably. Bioengineers synthesize DNA parts—oligonucleotides composed of 50–100 base pairs—which make specialized components that ultimately make a biological system. As biology becomes a true engineering discipline, bioengineers will create genomes using mass-produced modular units similar to the microelectronics and computer industries.

Currently, bioengineering projects cost millions of dollars and take years to develop products. For synthetic biology to become a Schumpeterian revolution, smaller companies will need to be able to afford to use bioengineering concepts for industrial applications. This will require standardized and automated processes.

A major challenge to developing synthetic biology is the complexity of biological systems. When bioengineers assemble synthetic parts, they must prevent cross talk between signals in other biological pathways. Until researchers better understand these undesired interactions that nature has already worked out, applications such as gene therapy will have unwanted side effects. Scientists do not fully understand the effects of environmental and developmental interaction on gene expression. Currently, bioengineers must repeatedly use trial and error to create predictable systems.

Similar to physics, synthetic biology requires the ability to model systems and quantify relationships between variables in biological systems at the molecular level.

The second major challenge to ensuring the success of synthetic biology is the development of enabling technologies. With genomes having billions of nucleotides, this requires fast, powerful, and cost-efficient computers. Moore’s law, named for Intel co-founder Gordon Moore, posits that computing power progresses at a predictable rate and that the number of components in integrated circuits doubles each year until its limits are reached. Since Moore’s prediction, computer power has increased at an exponential rate while pricing has declined.

DNA sequencers and synthesizers are necessary to identify genes and make synthetic DNA sequences. Bioengineer Robert Carlson calculated that the capabilities of DNA sequencers and synthesizers have followed a pattern similar to computing. This pattern, referred to as the Carlson Curve, projects that scientists are approaching the ability to sequence a human genome for $1,000, perhaps in 2020. Carlson calculated that the costs of reading and writing new genes and genomes are falling by a factor of two every 18–24 months. (see recent Carlson comment on requirement to read and write for a variety of limiting conditions).

Startup to Strengthen Synthetic Biology and Regenerative Medicine Industries with Cutting Edge Cell Products

http://pharmaceuticalintelligence.com/2013/11/28/startup-to-strengthen-synthetic-biology-and-regenerative-medicine-industries-with-cutting-edge-cell-products/

Synthetic Biology: On Advanced Genome Interpretation for Gene Variants and Pathways: What is the Genetic Base of Atherosclerosis and Loss of Arterial Elasticity with Aging

http://pharmaceuticalintelligence.com/2013/05/17/synthetic-biology-on-advanced-genome-interpretation-for-gene-variants-and-pathways-what-is-the-genetic-base-of-atherosclerosis-and-loss-of-arterial-elasticity-with-aging/

Synthesizing Synthetic Biology: PLOS Collections

http://pharmaceuticalintelligence.com/2012/08/17/synthesizing-synthetic-biology-plos-collections/

Capturing ten-color ultrasharp images of synthetic DNA structures resembling numerals 0 to 9

http://pharmaceuticalintelligence.com/2014/02/05/capturing-ten-color-ultrasharp-images-of-synthetic-dna-structures-resembling-numerals-0-to-9/

Silencing Cancers with Synthetic siRNAs

http://pharmaceuticalintelligence.com/2013/12/09/silencing-cancers-with-synthetic-sirnas/

Genomics Now—and Beyond the Bubble

Futurists have touted the twenty-first century as the century of biology based primarily on the promise of genomics. Medical researchers aim to use variations within genes as biomarkers for diseases, personalized treatments, and drug responses. Currently, we are experiencing a genomics bubble, but with advances in understanding biological complexity and the development of enabling technologies, synthetic biology is reviving optimism in many fields, particularly medicine.

BY MICHAEL BROOKS 17 APR, 2014 http://www.newstatesman.com/

Michael Brooks holds a PhD in quantum physics. He writes a weekly science column for the New Statesman, and his most recent book is The Secret Anarchy of Science.

The basic idea is that we take an organism – a bacterium, say – and re-engineer its genome so that it does something different. You might, for instance, make it ingest carbon dioxide from the atmosphere, process it and excrete crude oil.

That project is still under construction, but others, such as using synthesised DNA for data storage, have already been achieved. As evolution has proved, DNA is an extraordinarily stable medium that can preserve information for millions of years. In 2012, the Harvard geneticist George Church proved its potential by taking a book he had written, encoding it in a synthesised strand of DNA, and then making DNA sequencing machines read it back to him.

When we first started achieving such things it was costly and time-consuming and demanded extraordinary resources, such as those available to the millionaire biologist Craig Venter. Venter’s team spent most of the past two decades and tens of millions of dollars creating the first artificial organism, nicknamed “Synthia”. Using computer programs and robots that process the necessary chemicals, the team rebuilt the genome of the bacterium Mycoplasma mycoides from scratch. They also inserted a few watermarks and puzzles into the DNA sequence, partly as an identifying measure for safety’s sake, but mostly as a publicity stunt.

What they didn’t do was redesign the genome to do anything interesting. When the synthetic genome was inserted into an eviscerated bacterial cell, the new organism behaved exactly the same as its natural counterpart. Nevertheless, that Synthia, as Venter put it at the press conference to announce the research in 2010, was “the first self-replicating species we’ve had on the planet whose parent is a computer” made it a standout achievement.

Today, however, we have entered another era in synthetic biology and Venter faces stiff competition. The Steve Jobs to Venter’s Bill Gates is Jef Boeke, who researches yeast genetics at New York University.

Boeke wanted to redesign the yeast genome so that he could strip out various parts to see what they did. Because it took a private company a year to complete just a small part of the task, at a cost of $50,000, he realised he should go open-source. By teaching an undergraduate course on how to build a genome and teaming up with institutions all over the world, he has assembled a skilled workforce that, tinkering together, has made a synthetic chromosome for baker’s yeast.

Stepping into DIYbio and Synthetic Biology at ScienceHack

Posted April 22, 2014 by Heather McGaw and Kyrie Vala-Webb

We got a crash course on genetics and protein pathways, and then set out to design and build our own pathways using both the “Genomikon: Violacein Factory” kit and Synbiota platform. With Synbiota’s software, we dragged and dropped the enzymes to create the sequence that we were then going to build out. After a process of sketching ideas, mocking up pathways, and writing hypotheses, we were ready to start building!

The night stretched long, and at midnight we were forced to vacate the school. Not quite finished, we loaded our delicate bacteria, incubator, and boxes of gloves onto the bus and headed back to complete our bacterial transformation in one of our hotel rooms. Jammed in between the beds and the mini-fridge, we heat-shocked our bacteria in the hotel ice bucket. It was a surreal moment.

While waiting for our bacteria, we held an “unconference” where we explored bioethics, security and risk related to synthetic biology, 3D printing on Mars, patterns in juggling (with live demonstration!), and even did a Google Hangout with Rob Carlson. Every few hours, we would excitedly check in on our bacteria, looking for bacterial colonies and the purple hue characteristic of violacein.

Most impressive was the wildly successful and seamless integration of a diverse set of people: in a matter of hours, we were transformed from individual experts and practitioners in assorted fields into cohesive and passionate teams of DIY biologists and science hackers. The ability of everyone to connect and learn was a powerful experience, and over the course of just one weekend we were able to challenge each other and grow.

Returning to work on Monday, we were hungry for more. We wanted to find a way to bring the excitement and energy from the weekend into the studio and into the projects we’re working on. It struck us that there are strong parallels between design and DIYbio, and we knew there was an opportunity to bring some of the scientific approaches and curiosity into our studio.

Read Full Post »

Pharmacogenomics – A New Method for Druggability

Posted in Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cardiovascular Pharmacogenomics, Genome Biology, Genomic Testing: Methodology for Diagnosis, Medical and Population Genetics, Medical Devices R&D Investment, Metabolomics, Molecular Genetics & Pharmaceutical, Sensors & Analytics, Translational Science on April 28, 2014| Leave a Comment »

Pharmacogenomics – A New Method for Druggability

Author and Curator: Demet Sag, PhD

Living organisms have three main needs transfer of information, food and adopt to survive. As a result translational medicine utilizes the “genetic information”, to correct health problems that are acquired or earned at birth.

Translational Pharmacogenomics relates to durable genome against diseases, complex, congenital, orphan- uncommon and infectious diseases. Yet, there are caveats that need to be completed.

Hence, in this series I like to discuss clinical genomics, metabolomics and regulation of drugs by FDA to adopt what we need to what we can make. This is the new terminology trio of life replacing genetics, food and adoption to survive. Thus, genetics, genomics, bioinformatics, clinical research, clinical genomics and drugs make up part of the translational medicine in short this field classified under pharmacogenomics.

In 2003 there were two reviews on pharmacogenomics but there is a great jump in this area.

There are differences and similarities in genomics. When drug-ability is combined we can have a “pharmacogenetics” that directly uses genetics information to diagnose or fix the disease. Thus, “intellectual” screening may involves sequencing the whole genome or using a sensor to detect the specific piece of genome. This brings out the personalized medicine since each one of us has a unique genetic make- up.

Inconsistencies are part of the connection details where curation is the key to identify the real targets and eliminate the false targets for development of targets. There are inconsistencies that need to be identified. This can be observed in detail at Haibe-Kains et al, Nature reported “Inconsistency in large pharmacogenomic studies (PMID 24284626) or recent

Anticoagulant therapy is a game of tight balancing for the sake of patient as there are not many drugs to control blood coagulation mechanism properly during the course of drug treatment. As a result, anticoagulant therapy is a plausible area to discover new drug by pharmacokinetics to replace well known warfarin.

Coumarins have a wide range of use in clinics with a narrow therapeutic index drug with frequent hemorrhagic complications regardless of its dose adjustment because there are many clinical variables including age, gender, weight, nutritional factors, dietary vitamin K intake and interactive medications.

The ratio between cost and health outcomes is very important since the cost of warfarin adverse drug reactions is high and is estimated to exceed $180 billion dollars annually.

On the other hand, in average about 18-22 million dollar warfarin prescribed per year, in 2003 23 million, in 2006 19 million dollars etc. However, coagulation, and consequently, warfarin dose, is influenced by many other factors both physiological and genetic.

There has been a clinical trial on warfarin treatment based on genotype guided dosing but this study fail to present any improvement on anticoagulation control at the first 4 weeks of therapy, NCT00839657. However, neither patients nor doctors knew about the warfarin doses in the study that included 1015 patients to receive doses of warfarin during the first 5 days of therapy or 28 days. The doses determined by reported clinical outcomes and genotypes.

On the other hand, a total of 455 patients were recruited, with 227 randomly assigned to the genotype-guided group and 228 assigned to the control group. The mean percentage of time in the therapeutic range was 67.4% in the genotype-guided group as compared with 60.3% in the control group (adjusted difference, 7.0 percentage points; 95% confidence interval, 3.3 to 10.6; P<0.001). There were significantly fewer incidences of excessive anticoagulation (INR ≥4.0) in the genotype-guided group. The median time to reach a therapeutic INR was 21 days in the genotype-guided group as compared with 29 days in the control group (P<0.001).

Higashi et al also reported that the CYP2C9*2 and CYP2C9*3 polymorphisms may increase over anticoagulation and of bleeding thus it is plausible to suggest that screening for CYP2C9 polymorphisms may help clinicians in two ways. First improve dosing protocols. Second, prevent the risk of adverse drug reactions in patients receiving warfarin.

On the other hand, vitamin K epoxide reductase complex 1 (VKORC1) at transcriptional gene regulation level may gauge warfarin doses. They suggest that if one has certain variants the warfarin dose changes low, medium and high based on transcriptional level VKORC1 gene expression.

Thus, Tuan study showed that VKORC1 promoter mutation to identify if this results in any changes for warfarin dosing among population. . They found that Chinese population requires smaller dose than the Caucasians because patients with the −1639 promoter polymorphism AA genotype had lower dose requirements, whereas the AG/GG genotypes had higher dose requirements.

Yet, another study tried to relate warfarin dosing based on genetic mutations, CYP2C9 and VKORC1. However, the missing link of this study is excluding the SNPs and variations in other genes in the coagulation cascade that is affected by VKORC1 specially since VKORC1 play a role in vitamin K recycling and posttranslation that insures proper attachment of coagulation factors prothrombin, HFVII, HFIX and HFX.

Demographic variables	N = 495
SD, standard deviation; VKORC1, vitamin K epoxide reductase complex 1; CYP, cytochrome P 450. ^†The VKORC1 A haplotype can be detected by −1639 G > A.
Age, mean (SD), years	55 (13)
Gender
Female, n (%)	234 (47%)
Male, n (%)	261 (53%)
Race
Caucasian, n (%)	434 (88%)
African-American, n (%)	47 (9%)
Other, n (%)	14 (3%)
Hispanic ethnicity, n (%)	6 (1%)
Genetic variables
VKORC1 A haplotype^† frequency	37.5%
CYP2C9*2 allele frequency	12.2%
CYP2C9*3 allele frequency	6.4%
Clinical variables
Geometric mean warfarin dose, mg per day, (SD)	4.4 (1.5)
Body surface area, in m² mean (SD)	2.05 (0.27)
Smoker, n (%)	57 (12%)
Takes statin, n (%)	53 (11%)
Takes amiodarone, n (%)	0 (0%)
Takes aspirin, n (%)	97 (20%)
Table 1. Demographic, genetic and clinical characteristics of participants

Figure 1. Percentage of dose variation explained at weekly time points.

	Day 0 (%)	Day 7 (%)	Day 14 (%)	Day 21 (%)
Genetic	42.8	12.1	3.9	1.4
Clinical	10.8	6.4	2.2	1.9
INR	0	31.7	19.1	5.1
Prior dose	0	18.0	50.3	68.6
TOTAL	53.6	68.1	75.4	77.0
Table 2. Percentage of dose variation explained (partial R²) at weekly time points

In summary,

we found that SNPs causing slower warfarin metabolism and increased warfarin sensitivity account for signiﬁcant variability of therapeutic warfarin dose. These SNPs

are associated with increased risk of supratherapeutic INRs up to 28 days after initiation. However, the importance of genotype wanes over the initial weeks of therapy. Our ﬁndings

should prompt future studies to develop and assess the clinical utility of a day 7 pharmacogenetic dosing algorithm.

There are controversial studies or conflicting reports that needs to be elucidated with good bioinformatics tools as well as well done curation of available data. After all the work CYP2C9 and VKORC1 genotypes defined as key factors and about 30 to 40% of the total variation in the final warfarin dose. Patients for variations in CYP2C9 and VKORC1 provide information to enhance clinical algorithms currently.

Clinicians should apply genomics tools for maintain anticoagulant therapy for their patients.

SOURCE

A pharmacogenetic versus a clinical algorithm for warfarin dosing.

Kimmel SE, French B, Kasner SE, Johnson JA, Anderson JL, Gage BF, Rosenberg YD, Eby CS, Madigan RA, McBane RB, Abdel-Rahman SZ, Stevens SM, Yale S, Mohler ER 3rd, Fang MC, Shah V, Horenstein RB, Limdi NA, Muldowney JA 3rd, Gujral J, Delafontaine P, Desnick RJ, Ortel TL, Billett HH, Pendleton RC, Geller NL, Halperin JL, Goldhaber SZ, Caldwell MD, Califf RM, Ellenberg JH; COAG Investigators.

N Engl J Med. 2013 Dec 12;369(24):2283-93. doi: 10.1056/NEJMoa1310669. Epub 2013 Nov 19. PMID:24251361

http://www.ncbi.nlm.nih.gov/pubmed/24251361

A randomized trial of genotype-guided dosing of warfarin

Pirmohamed M¹, Burnside G, Eriksson N, Jorgensen AL, Toh CH, Nicholson T, Kesteven P, Christersson C, Wahlström B, Stafberg C, Zhang JE, Leathart JB,Kohnke H, Maitland-van der Zee AH, Williamson PR, Daly AK, Avery P, Kamali F, Wadelius M; EU-PACT Group.

N Engl J Med. 2013 Dec 12;369(24):2294-303. doi: 10.1056/NEJMoa1311386. Epub 2013 Nov 19.

A novel functional VKORC1 promoter polymorphism is associated with inter-individual and inter-ethnic differences in warfarin sensitivity.

Yuan HY, Chen JJ, Lee MT, Wung JC, Chen YF, Charng MJ, Lu MJ, Hung CR, Wei CY, Chen CH, Wu JY, Chen YTHum Mol Genet 2005; 14: 1745–51.

Genotypes of the cytochrome p450 isoform, CYP2C9, and the vitamin K epoxide reductase complex subunit 1 conjointly determine stable warfarin dose: a prospective study.

Carlquist JF, Horne BD, Muhlestein JB, Lappe DL, Whiting BM, Kolek MJ, Clarke JL, James BC, Anderson JL. J Thromb Thrombolysis 2006; 22: 191–7.

Pharmacogenomics for Cardiovascular Diseases

Blood Pressure Response to Antihypertensives: Hypertension Susceptibility Loci Study

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/blood-pressure-response-to-antihypertensives-atenolol-and-hydrochlorothiazide-hypertension-susceptibility-loci-study/

Statin-Induced Low-Density Lipoprotein Cholesterol Reduction: Genetic Determinants in the Response to Rosuvastatin

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/statin-induced-low-density-lipoprotein-cholesterol-reduction-genetic-determinants-in-the-response-to-rosuvastatin/

SNPs in apoE are found to influence statin response significantly. Less frequent variants in PCSK9 and smaller effect sizes in SNPs in HMGCR

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/snps-in-apoe-are-found-to-influence-statin-response-significantly-less-frequent-variants-in-pcsk9-and-smaller-effect-sizes-in-snps-in-hmgcr/

Voltage-Gated Calcium Channel and Pharmacogenetic Association with Adverse Cardiovascular Outcomes: Hypertension Treatment with Verapamil SR (CCB) vs Atenolol (BB) or Trandolapril (ACE)

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/voltage-gated-calcium-channel-and-pharmacogenetic-association-with-adverse-cardiovascular-outcomes-hypertension-treatment-with-verapamil-sr-ccb-vs-atenolol-bb-or-trandolapril-ace/

Response to Rosuvastatin in Patients With Acute Myocardial Infarction: Hepatic Metabolism and Transporter Gene Variants Effect

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/response-to-rosuvastatin-in-patients-with-acute-myocardial-infarction-hepatic-metabolism-and-transporter-gene-variants-effect/

Helping Physicians identify Gene-Drug Interactions for Treatment Decisions: New ‘CLIPMERGE’ program – Personalized Medicine @ The Mount Sinai Medical Center

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/04/15/helping-physicians-identify-gene-drug-interactions-for-treatment-decisions-new-clipmerge-program-personalized-medicine-the-mount-sinai-medical-center/

Leveraging Mathematical Models to Understand Population Variability in Response to Cardiac Drugs: Eric Sobie, PhD

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/04/22/leveraging-mathematical-mod

els-to-understand-population-variability-in-response-to-cardiac-drugs-eric-s

obie-phd/

Is Pharmacogenetic-based Dosing of Warfarin Superior for Anticoagulation Control?

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/02/04/is-pharmacogenetic-based-dosing-of-warfarin-superior-for-anticoagulation-control/

Read Full Post »

Acetylation and Deacetylation of non-Histone Proteins

Posted in Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Genome Biology, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Nitric Oxide in Health and Disease, Nutrigenomics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Signaling, tagged acetylation and deacetylation, non-histone proteins, Proteomics, PTM on April 22, 2014| Leave a Comment »

Acetylation and Deacetylation of non-Histone Proteins

Author and Curator: Larry H Bernstein, MD, FCAP

Acetylation and Deacetylation of non-histone proteins

MA Glozak, N Sengupta, X Zhang, E Seto
Gene 2005; 363(19): 15-23 http://dx.doi.org/10.1016/j.gene.2005.09.010

Since the first report of p53 as a non-histone target of a histone acetyltransferase (HAT), there has been a rapid proliferation in the description of new non-histone targets of HATs. Of these,

transcription factors comprise the largest class of new targets.

The substrates for HATs extend to

cytoskeletal proteins,
molecular chaperones and
nuclear import factors.

Deacetylation of these non-histone proteins by histone deacetylases (HDACs) opens yet another exciting new field of discovery in

the role of the dynamic acetylation and deacetylation on cellular function.

This review will focus on these non-histone targets of HATs and HDACs and the consequences of their modification.

Abbreviations:

HAT, histone acetyltransferase; HDAC, histone deacetylase; TSA, trichostatin A; CtBP, C-terminal binding protein; YY1, yin yang 1; HMG, high mobility group; NR, nuclear receptor; AR, androgen receptor; ER α, estrogen receptor α; SHP, short heterodimer partner; EKLF, erythroid Kruppel like factor; Rb, retinoblastoma; GR, glucocorticoid receptor; HDV, hepatitis delta virus; L-HDAg, large delta antigen; S-HDAg, small delta antigen

Keywords HATs; HDACs; Post-translational modification

Histone deacetylases (EC 3.5.1.98, HDAC) are a class of enzymes that

remove acetyl groups (O=C-CH₃) from an ε-N-acetyl lysine amino acid on a histone,
allowing the histones to wrap the DNA more tightly.

This is important because DNA is wrapped around histones, and

DNA expression is regulated by acetylation and de-acetylation.

Its action is opposite to that of histone acetyltransferase. HDAC proteins are now also called

lysine deacetylases (KDAC),
to describe their function rather than their target, which also
includes non-histone proteins

Histone modification

Histone tails are normally positively charged due to

amine groups present on their lysine and arginine amino acids.

These positive charges help the histone tails to

interact with and bind to the negatively charged phosphate groups on the DNA backbone.

Acetylation, which occurs normally in a cell,

neutralizes the positive charges on the histone by changing amines into amides and
decreases the ability of the histones to bind to DNA.

This decreased binding

allows chromatin expansion,
permitting genetic transcription to take place.

Histone deacetylases

remove those acetyl groups,
increasing the positive charge of histone tails and
encouraging high-affinity binding between the histones and DNA backbone.

The increased DNA binding

condenses DNA structure,
preventing transcription.

Histone deacetylase is involved in a series of pathways within the living system. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG), these are:

Environmental information processing; signal transduction; notch signaling pathway PATH:ko04330
Cellular processes; cell growth and death; cell cycle PATH:ko04110
Human diseases; cancers; chronic myeloid leukemia PATH:ko05220

Histone acetylation plays an important role in the regulation of gene expression.

Hyperacetylated chromatin is

transcriptionally active, and

hypoacetylated chromatin

is silent.

A study on mice found that a

specific subset of mouse genes (7%) was
- deregulated in the absence of HDAC1.^[10]

Their study also found a

regulatory crosstalk between HDAC1 and HDAC2 and suggest
- a novel function for HDAC1 as a transcriptional coactivator.

HDAC1 expression was found to be

increased in the prefrontal cortex of schizophrenia subjects,^[11]
negatively correlating with the expression of GAD67 mRNA.

Non-histone effects

It is a mistake to regard HDACs solely in the context of regulating gene transcription by modifying histones and chromatin structure, although

that appears to be the predominant function.

The function, activity, and stability of proteins can be controlled by

post-translational modifications.

Protein phosphorylation is perhaps the most widely studied and understood modification in which

certain amino acid residues are phosphorylated by the action of protein kinases or
dephosphorylated by the action of phosphatases.

The acetylation of lysine residues is emerging as an analogous mechanism, in which

non-histone proteins are acted on by acetylases and deacetylases.^[12]

It is in this context that HDACs are being found to interact with a variety of non-histone proteins—

some of these are transcription factors and co-regulators, some are not. Note the following four examples:

HDAC6 is associated with aggresomes.Misfolded protein aggregates are
- tagged by ubiquitination and removed from the cytoplasm by dynein motors via the microtubule network to an organelle termed the aggresome.
- HDAC 6 binds polyubiquitinated misfolded proteins and links to dynein motors, thereby
- allowing the misfolded protein cargo to be physically transported to chaperones and proteasomes for subsequent destruction.^[13]
PTEN is an important phosphatase involved in cell signaling via phosphoinositols and the AKT/PI3 kinase pathway.
- PTEN is subject to complex regulatory control via phosphorylation, ubiquitination, oxidation and acetylation.
- Acetylation of PTEN by the histone acetyltransferase p300/CBP-associated factor (PCAF) can repress its activity; on the converse,
- deacetylation of PTEN by SIRT1 deacetylase and, by HDAC1, can stimulate its activity.^[14][15]
APE1/Ref-1 (APEX1) is a multifunctional protein possessing both
- DNA repair activity (on abasic and single-strand break sites) and
- transcriptional regulatory activity associated with oxidative stress.
- APE1/Ref-1isacetylatedbyPCAF; on the converse,
  - it is stably associated with and deacetylated by Class I HDACs.
- The acetylation state of APE1/Ref-1 does not appear to affect its DNA repair activity, but it does
  - regulate its transcriptional activity such as
  - its ability to bind to the PTH promoter and initiate transcription of the parathyroid hormone gene.^[16][17]
NF-κB is a key transcription factor and
- effector molecule involved in responses to cell stress, consisting of a p50/p65 heterodimer.
- The p65 subunit is controlled by acetylation via PCAF and by deacetylation via HDAC3 and HDAC6.^[18]

HDAC inhibitors

Main article: Histone deacetylase inhibitor

Histone deacetylase inhibitors (HDIs) have a long history of use in psychiatry and neurology as mood stabilizers and anti-epileptics,

for example, valproic acid.

In more recent times, HDIs are being studied as

a mitigator or treatment for neurodegenerative diseases.^[19][20]
there has been an effort to develop HDIs for cancer therapy.^[21][22]

Vorinostat (SAHA) was approved in 2006 for the treatment of cutaneous manifestations in patients with cutaneous T cell lymphoma (CTCL) that have failed previous treatments.
A second HDI, Istodax (romidepsin), was approved in 2009 for patients with CTCL.

The exact mechanisms by which the compounds may work are unclear, but

epigenetic pathways are proposed.^[23] In addition, a clinical trial is studying valproic acid effects on the latent pools of HIV in infected persons.^[24]

HDIs are currently being investigated as chemosensitizers for

cytotoxic chemotherapy or radiation therapy, or in association with DNA methylation inhibitors based on in vitro synergy.^[25]

Recent research has focused on developing isoform selective HDIs which can aid in elucidating role of

individual HDAC isoforms and device strategy for effective treatment of
diseases related to relevant HDAC isoform.^[26][27][28]

HDAC inhibitors have effects on non-histone proteins that are related to acetylation. HDIs can

alter the degree of acetylation of these molecules and, therefore,
increase or repress their activity.

For the four examples given above (see Function) on HDACs acting on non-histone proteins, in each of those instances

the HDAC inhibitor Trichostatin A (TSA) blocks the effect.

HDIs have been shown to alter the activity of many transcription factors, including

ACTR, cMyb, E2F1, EKLF, FEN 1, GATA, HNF-4, HSP90, Ku70, NFκB, PCNA, p53, RB, Runx, SF1 Sp3, STAT, TFIIE, TCF, YY1.^[29][30]

To carry out gene expression, a cell must control the coiling and uncoiling of DNA around histones. This is accomplished with the assistance of histone acetyl transferases (HAT), which

acetylate the lysine residues in core histones leading to
- a less compact and more transcriptionally active chromatin, and, on the converse,
the actions of histone deacetylases (HDAC), which

remove the acetyl groups from the lysine residues
leading to the formation of a condensed and transcriptionally silenced chromatin.

Reversible modification of the terminal tails of core histones constitutes

the major epigenetic mechanism for remodeling higher-order chromatin structure and controlling gene expression.

HDAC inhibitors (HDI) block this action and

can result in hyperacetylation of histones, thereby affecting gene expression.^[5][6][7]

The histone deacetylase inhibitors are a new class of cytostatic agents that inhibit the proliferation of tumor cells in culture and in vivo

by inducing cell cycle arrest,
differentiation
and/or apoptosis.

Histone deacetylase inhibitors exert their anti-tumour effects via

the induction of expression changes of oncogenes or tumour suppressor, through
modulating that the acetylation/deactylation of histones and/or non-histone proteins such as transcription factors^[8].

Histone acetylation and deacetylation play important roles in the modulation of chromatin topology and the regulation of gene transcription.

Histone deacetylase inhibition induces

the accumulation of hyperacetylated nucleosome core histones in most regions of chromatin

but affects the expression of only a small subset of genes, leading to transcriptional activation of some genes, but repression of an equal or larger number of other genes.

Non-histone proteins such as transcription factors are also targets for acetylation with varying functional effects. Acetylation

enhances the activity of some transcription factors such as the tumor suppressor p53 and
the erythroid differentiation factor GATA-1
but may repress transcriptional activity of others including T cell factor and the co-activator ACTR.

Recent studies […] have shown that the estrogen receptor alpha (ERalpha) can be hyperacetylated

in response to histone deacetylase inhibition,
suppressing ligand sensitivity and regulating transcriptional activation by histone deacetylase inhibitors.^[9]

Conservation of the acetylated ER-alpha motif in other nuclear receptors suggests that

acetylation may play an important regulatory role in diverse nuclear receptor signaling functions.

A number of structurally diverse histone deacetylase inhibitors have shown potent antitumor efficacy with little toxicity in vivo in animal models. Several compounds are currently in early phase clinical development as potential treatments for solid and hematological cancers both as monotherapy and in combination with cytotoxics and differentiation agents.”^[10]

HDIs MI · Granger, A.; Abdullah, I.; Huebner, F.; Stout, A.; Wang, T.; Huebner, T.; Epstein, J. A.; Gruber, P. J. (2008). “Histone deacetylase inhibition reduces myocardial ischemia-reperfusion injury in mice”. The FASEB Journal 22 (10): 3549–60. http://dx.doi.org/10.1096/fj.08-108548. PMC 2537432. PMID 18606865.

Protein Acetylation: Much More than Histone Acetylation

By Tom Brock, Ph.D.

Just last decade, everyone was excited about the Human Genome Project, and the gene was king. Today, epigenetics is reminding us that

non-genetic factors are important in shaping gene expression and development.

Similarly, where phosphorylation once seemed the primary way to modulate proteins,

epigenetics has re-introduced us to acetylation as an important force in defining protein function.

In particular, the acetylation of histones has moved to center stage, even though it was described over 45 years ago. Research on histone acetylation has

led to a resurgence in the interest in enzymatically-mediated acetylation of other proteins.

This article examines acetylation as a post-translational modification of proteins that impacts gene expression and plays a role in epigenetics.

The Basics

Acetylation refers to the addition of an acetyl group (CH₃CO) to organic compounds. Proteins can be acetylated by both enzymatic and non-enzymatic processes.

One group of acetyltransferases commonly catalyze the transfer of an acetyl group from acetyl-CoA to the terminal amine on the side chain of lysine residues (Figure 1).

These enzymes are commonly called HATs, because their best-known substrates have been histones.

However, the nomenclature is being revised to lysine acetyltransferases (KATs), reflecting their ability to acetylate lysine (denoted ‘K’) on many proteins.

¹ The KATs are numerous, with many assigned, based on structural similarities, to either

the GNAT (Gcn5-related N-acetyltransferases) superfamily or
the MYST (MOZ, YBF2/Sas3, Sas2, Tip60) family.

Other important KATs include

p300 (E1A-associated protein 300 kDa),
CBP (cAMP response element binding (CREB)-binding protein), and
TAFII 250 (TATA-binding protein associated factor II 250).

The conversion of the positively charged lysine to acetyl-lysine, like the addition of negative phosphates to uncharged amino acids during phosphorylation,

alters protein structure and interactions with other biomolecules. For example, acetylation of histones typically

promotes the recruitment of effector proteins,
relaxation of chromatin conformation, and
an increase in transcription.

Like phosphorylation,

acetylation is reversible.

Histone deacetylases (HDACs, a.k.a. KDACs) are a smaller group of evolutionarily conserved enzymes.

The human class I HDACs are

homologous to the yeast enzyme Rpd3 and include HDAC1, 2, 3, and 8.

Class II HDACs are

homologous to yeast HDA1 and are divided into class IIa (HDAC4, 5, 7, 9) and class IIb (HDAC6 and 10) based on structure.
The human class III HDACs include the sirtuin family of NAD⁺-dependent protein deacetylases.
The novel HDAC11 has a distinct structure and is a class IV HDAC.

The HDACs often participate in the formation of transcriptional repressor complexes, inducing

chromatin compaction through histone deacetylation, and silencing gene expression.

A Diversity of Partners

A great resource for the research scientist is the National Center for Biotechnology Information (NCBI), your tax dollars at work compiling information about everything molecular. This site should be your first stopping point when trying to learn authoritative information about a new protein or gene that you’re studying. Information at this site helps to underscore two points about KATs and deacetylases: they are social enzymes, always interacting with other proteins, and they are promiscuous, binding to an astounding array of partners. Take, for example, the KAT known commonly as p300. At the NCBI gene link, entering ‘human p300’ finds the gene EP300 (KAT3B), with a summary stating that it associates with the adenovirus protein E1A, acetylates histones, binds CREB, and is a co-activator of HIF-1α (hypoxia-inducible factor 1α). Further down, we find that it binds three different proteins produced by the lentivirus human immunodeficiency virus (HIV)-1. Then, impressively, is a list of over two hundred proteins that have been documented to directly interact with p300 (with links to references and other interactome datasets included). Similarly, the deacetylase HDAC1 is summarized as a histone deacetylase that also interacts with retinoblastoma tumor-suppressor to control cell growth and, together with metastasis-associated protein-2, deacetylates the tumor suppressor p53. Like p300, HDAC1 has an amazing list of partners: it interacts with some 300 proteins, with over 125 of these documented as direct binding partners.

The abundance of protein partners, for both KATs and HDACs, suggests that these enzymes tend to form multimeric complexes. In fact, such complexes serve the critical purpose of positioning the (de)acetylases at specific sites to perform their functions. Certainly, KATs can directly acetylate substrates in vitro. However, KAT activity in vivo is regulated, at least in part, by where it is positioned. For example, the classical model for activation of PPARs (peroxisome proliferator-activated receptors) posits that this receptor heterodimerizes at specific response elements with RXR (retinoid X receptor). In the absence of ligand, the unactivated heterodimer binds co-repressor proteins, such as nuclear receptor co-repressors (NCoR), G-protein pathways suppressor 2 (GPS2), and HDACs (Figure 2). The HDACs help prevent expression of PPAR-specific genes by keeping the neighboring histones deacetylated. The appearance of a ligand for PPAR causes dissociation of the co-repressor proteins followed by the recruitment of co-activators, including PPAR co-activator (PGC-1), CREB binding protein (CBP), and p300. Formation of the PPAR activation complex leads to histone acetylation by CBP and p300, giving rise to altered expression of genes involved in fatty acid metabolism, lipid homeostasis, and adipocyte differentiation. In this example, ligand binding to its receptor causes a large scale switch from a cluster of proteins serving various roles in preventing transcription to a different group designed to facilitate gene transcription.

Acetylation Patterns

In its simplest form acetylation is merely another form of post-translational modification of proteins. A good example is the acetylation of tubulin, which can be deacetylated by HDAC6 or SIRT2. Acetylation of this key microtubule component appears to alter its affinity for kinesin-1 and redirect motor-based trafficking of vesicles.^2,3 In short, acetylation changes protein function by adjusting protein-protein interactions. The net ‘global’ acetylation, in this case, may be determined by the balance of overall KAT and HDAC activities.

More commonly, acetylation is targeted to specific proteins and, possibly, specific lysine residues on those protein targets. One way that this can be achieved is by the formation of protein complexes containing either KATs or HDACs, as in the PPAR case described above. The assembly of the complex serves to place the KATs/HDACs near histones, transcription factors, or other targets. Histones, assembled as an octamer core surrounded by DNA, have amino termini that are freely exposed (Figure 3). Positively-charged lysine residues on these tails interact electrostatically with negatively-charged phosphate groups along the DNA backbone. Acetylation reduces these interactions and loosens the DNA, facilitating transcription. Bear in mind that, while it is generally true that histone acetylation increases transcriptional activation, there are exceptions. For example, acetylation of estrogen receptor-α suppresses ligand sensitivity and reduces ligand-induced transcriptional activity.^4,5

References

1. Glozak, M.A., Sengubpta, N., Zhang, X., et al. Gene 363, 15-23 (2005).

2. Hammond, J.W., Cai, D., and Verhey, K.J. Curr. Opin. Cell Biol. 20, 71-76 (2008).

3. Gao, Y., Hubber, C.C., and Yao, T.P. J. Biol. Chem. epub ahead of print (2010).

4. Wang, C., Fu, M., Angeletti, R.H., et al. J. Biol. Chem. 276, 18375-18383 (2001).

5. Popov, V.M., Wang, C., Shirley, L.A., et al. Steroids 72, 221-230 (2007).

6. Mellert, H.S. and McMahon, S.B. Trends Biochem. Sci. 34, 571-578 (2009).

7. Yang, X.J. and Seto, E. Mol. Cell 31, 49-461 (2008).

8. Wilson, A.J., Byun, D.S., Popova, N., et al. J. Biol. Chem. 281, 13548-13558 (2006).

9. Vincent, A. and Van Seuningen, I. Differentiation 78, 99-107 (2009).

10. Li, Z., Chen, L., Kabra, N., et al. J. Biol. Chem. 284, 10361-10366 (2009).

From Protein Acetylation: Much More than Histone Acetylation by Brock, T.G.

2 Figures saved

PTM modifications

3-d-genome-map

graphs_superdex-both-high-resolution-size-exclusion-gel-filtration-chromatography

Read Full Post »

PostTranslational Modification of Proteins

Posted in Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Epigenetics and Cardiovascular Risks, Medical and Population Genetics, Metabolomics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Proteomics, tagged cell signalling, metabolic regulation, post translational modifications, Proteomics on April 21, 2014| Leave a Comment »

PostTranslational Modification of Proteins

Author and Curator: Larry H Bernstein, MD, FCAP

Posttranslational modification of proteins: expanding nature’s inventory.

Walsh, Christopher T.
Roberts & Company Publishers 2006
Englewood, Colo.: xxi, 490

For students of protein structure, metabolism, and cellular signaling, Walsh (biological chemistry, molecular pharmacology, Harvard Medical School), a leading enzymologist, examines major classes of posttranslational modifications (PTMs) that account for the diversity of protein structure and function in living cells. He contributes to emerging knowledge,
relevant to pharmaceutical intervention,

of the enzymes involved in generating PTMs, i.e.,

changes that occur after messenger RNA code has been translated into the amino acid sequence code of nascent proteins.

The text contains numerous examples of the role PTMs play in signal transduction and metabolism, and crisp color illustrations.

The Quarterly Review of Biology, Vol. 83, No. 4. (1 December 2008), pp. 403-403, http://dx.doi.org/10.1086/596250 Key: citeulike:3682226

Peptidylglycine alpha-amidating monooxygenase: A multifunctional protein with catalytic, processing, and routing domains

by Betty A. Eipper, Sharon L. Milgram, E. Jean Husten, Hye-Young Yun, Richard E. Mains

Protein Science 1993; 2(4): pp. 489-497, http://dx.doi.org10.1002/pro.5560020401

Overview of Post-Translational Modifications (PTMs) Analysis:

PTMs(hereafter): Phosphorylation (pS/T, pY), Methylation, Deamidation, Oxidation, Nitration, N-glycosylation, Amino acid mutation, Unnatural amino acid, Chemical modifications, Palmitoylation, Glycosylation, Ubiquitination, SUMOylation, Dimethylation, Acetylation, Decarboxylation, etc..

Protein post-translational modification (PTM) increases the functional diversity of the proteome by the covalent addition of functional groups or proteins, proteolytic cleavage of regulatory subunits or degradation of entire proteins. These modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis and influence almost all aspects of normal cell biology and pathogenesis. Therefore, identifying and understanding PTMs is critical in the study of cell biology and disease treatment and prevention.

1) Significance:

Protein post-translational modifications play a key role in many cellular processes such as cellular differentiation (Grotenbreg and Ploegh, 2007), protein degradation (Geiss-Friedlander and Melchior, 2007), signaling and regulatory processes (Morrison, et al 2002), regulation of gene expression, and protein-protein interactions. These modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation and proteolysis and influence almost all aspects of normal cell biology and pathogenesis. Therefore, identifying and understanding PTMs is critical in the study of cell biology and disease treatment and prevention.

PTM modifications

2) Post-translational modifications are key mechanisms to increase proteomic diversity.

While the human genome comprises 20-25,000 genes, the proteome is estimated to encompass over 1 million proteins. Changes at the transcriptional and mRNA levels increase the size of the transcriptome relative to the genome, and the myriad of different post-translational modifications exponentially increases the complexity of the proteome relative to both the transcriptome and genome.

a) Some Modifications (Phosphorylations, etc.) are easier to find than others. We can look for specific modifications or unknown modifications.

b) As a general rule, any post-translational modification (PTM) could be searched for in your protein as long as we know the mass added by the modification and the potentially modified amino acid (e.g. in the case of phosphorylation: +80 Da on a Serine, Threonine or Tyrosine).

PTM (Post-Translational Modification) Analysis http://www.creative-proteomics.com/protein-post-translational-modification-analysis.htm#1._Overview_of_Post-Translational_Modifications_%28PTMs%29_Analysis

Jose Eduardo de Salles Roselino:

The easy way to look at protein is to present it as a by-product of DNA. However, protein must be viewed as central macromolecule in biology since; even DNA is made from building blocks by protein activity. DNA are the reservoir of genetic information that establishes amino acid in proteins.
In normal living beings, normality defined by general health parameters whose values are inside an acceptable range of variation. Normal here is a statistical idea, as it must be and not as presented in recent years, as a living being that has a genome that does not have “glitches”, or a genome that would be defined as an ideal or a perfect genome.
In line with this idea, protein receives the information that determines its amino acid sequence from DNA but have its conformation, activity and function derived from its ability to change its conformation in response to changes in its microenvironment and environment. These changes in conformation are in a form adequate to keep those parameters mentioned above inside the range that define the idea of normality in accordance with the condition in which the living being is, both in time (development) as well as in space.
Therefore, post-translational must indicate a clear cut in the domain of DNA influence and not something, which is also derived from this DNA-centric view. This distortion of biochemistry has led to the never-ending genetics of non-genetic diseases. Genetics appears in inborn errors that are not acquired and show its effects in defects of proteins that could be established by a change in the DNA. Normality, or lack of abnormal genetic defect are perceived in all genomes that are able to maintain inside the normality range those parameters that define normal under defined circumstances. When this view is taken into account, DNA is take into account only when genetic diseases are considered. For the majority of the cases the scheme here presented must be made for each kind of cell, in each organ or system and the posttranslational changes thus, presented as function of development and/or a required fast regulatory change necessary to keep a cell and the organisms in general inside the normal range.

Read Full Post »

Cancer Research: Curations and Reporting: Aviva Lev-Ari, PhD, RN

Posted in CANCER BIOLOGY & Innovations in Cancer Therapy, Medical and Population Genetics, Personalized and Precision Medicine & Genomic Research on April 20, 2014| Leave a Comment »

Cancer Research: Curations and Reporting: Aviva Lev-Ari, PhD, RN

Curator: Aviva Lev-Ari, PhD, RN

General

Lev-Ari, A. 7/5/2013, “2013 Perspective on “War on Cancer” on December 23, 1971

http://pharmaceuticalintelligence.com/2013/07/05/2013-perspective-on-war-on-cancer-on-december-23-1971/

Lev-Ari, A. 3/24/2013, New Ecosystem of Cancer Research: Cross Institutional Team Science

http://pharmaceuticalintelligence.com/2013/03/24/new-ecosystem-of-cancer-research-cross-institutional-team-science/

Lev-Ari, A. 7/25/2013, Family History of Cancer may increase the Risk of Close Relatives developing the Same Type of Cancer as well as Different Types

http://pharmaceuticalintelligence.com/2013/07/25/family-history-of-cancer-may-increase-the-risk-of-close-relatives-developing-the-same-type-of-cancer-as-well-as-different-types/

Lev-Ari, A. 4/12/2013, 2013 American Cancer Research Association Award for Outstanding Achievement in Chemistry in Cancer Research: Professor Alexander Levitzki

http://pharmaceuticalintelligence.com/2013/04/12/2013-american-cancer-research-association-award-for-outstanding-achievement-in-chemistry-in-cancer-research-professor-alexander-levitzki-chosen/

Lev-Ari, A. 6/12/2013, Bioenergetic Mechanism: The Inverse Association of Cancer and Alzheimer’s

http://pharmaceuticalintelligence.com/2013/06/12/bioenergetic-mechanism-the-inverse-association-of-cancer-and-alzheimers/

Lev-Ari, A. 1/12/2013, “Harnessing Personalized Medicine for Cancer Management, Prospects of Prevention and Cure: Opinions of Cancer Scientific Leaders @ http://pharmaceuticalintelligence.com“

http://pharmaceuticalintelligence.com/2013/01/12/harnessing-personalized-medicine-for-cancer-management-prospects-of-prevention-and-cure-opinions-of-cancer-scientific-leaders-httppharmaceuticalintelligence-com/

Lev-Ari, A. 12/1/2012, Personalized Medicine: Cancer Cell Biology and Minimally Invasive Surgery (MIS)

http://pharmaceuticalintelligence.com/2012/12/01/personalized-medicine-cancer-cell-biology-and-minimally-invasive-surgery-mis/

Lev-Ari, A. 4/8/2013, Amiodarone Linked to Cancer Risk in Men

http://pharmaceuticalintelligence.com/2013/04/08/amiodarone-linked-to-cancer-risk-in-men/

Reporting

New Biomarker for Esophageal Cancer Reported in the Journal “Cancer Research”

http://pharmaceuticalintelligence.com/2014/01/22/new-biomarker-for-esophageal-cancer-reported-in-the-journal-cancer-research/

Artificial Pancreas: A UK Biotech Invention – Potential for Replacement to Insulin Injections

http://pharmaceuticalintelligence.com/2014/01/27/artificial-pancreas-a-uk-biotech-invention-potential-for-replacement-to-insulin-injections/

Positron Emission Tomography (PET) and Near-Infrared Fluorescence Imaging: Noninvasive Imaging of Cancer Stem Cells (CSCs) monitoring of AC133+ glioblastoma in subcutaneous and intracerebral xenograft tumors

http://pharmaceuticalintelligence.com/2014/01/29/positron-emission-tomography-pet-and-near-infrared-fluorescence-imaging-noninvasive-imaging-of-cancer-stem-cells-cscs-monitoring-of-ac133-glioblastoma-in-subcutaneous-and-intracerebral-xenogra/

Efficacy of Ovariectomy in Presence of BRCA1 vs BRCA2 and the Risk for Ovarian Cancer

http://pharmaceuticalintelligence.com/2014/02/25/efficacy-of-ovariectomy-in-presence-of-brca1-vs-brca2-and-the-risk-for-ovarian-cancer/

Oncologists ordered 3,752 FoundationOne clinical test: 200 cancer-related genes analysis — Revenues Climb 87% in Q4 2013

http://pharmaceuticalintelligence.com/2014/02/26/oncologists-ordered-3752-foundationone-clinical-test-200-cancer-related-genes-analysis-revenues-climb-87-in-q4-2013/

Alternative to Imaging (potentially): Urine Test developed by MIT – A Paper Diagnostics amplifies Signals from Growing Tumors to detect Cancer

http://pharmaceuticalintelligence.com/2014/03/03/alternative-to-imaging-potentially-urine-test-developed-by-mit-a-paper-diagnostics-amplifies-signals-from-growing-tumors-to-detect-cancer/

Gene Therapy and the Genetic Study of Disease: @Berkeley and @UCSF – New DNA-editing technology spawns bold UC initiative as Crispr Goes Global

http://pharmaceuticalintelligence.com/2014/03/27/gene-therapy-and-the-genetic-study-of-disease-berkeley-and-ucsf-new-dna-editing-technology-spawns-bold-uc-initiative-as-crispr-goes-global/

Alterations in the ACVR1 Gene can contribute to a Rare, typically Fatal Form of Childhood Brainstem Cancer called Diffuse Intrinsic Pontine Glioma (DIPG).

http://pharmaceuticalintelligence.com/2014/04/10/alterations-in-the-acvr1-gene-can-contribute-to-a-rare-typically-fatal-form-of-childhood-brainstem-cancer-called-diffuse-intrinsic-pontine-glioma-dipg/

Novel Therapies for Cancer

Lev-Ari, A. 5/16/2013, AT13148 – A Novel Oral Multi-AGC Kinase Inhibitor Has Potent Antitumor Activity

http://pharmaceuticalintelligence.com/2013/05/16/at13148-a-novel-oral-multi-agc-kinase-inhibitor-has-potent-antitumor-activity/

Lev-Ari, A. 4/22/2013, “System Pharmacology: Using CellMiner and the NCI-60 Cancerous Cell Lines: William Reinhold, PhD”

http://pharmaceuticalintelligence.com/2013/04/22/system-pharmacology-using-cellminer-and-the-nci-60-cancerous-cell-lines-william-reinhold-phd/

Lev-Ari, A. 2/10/2013, Global Burden of Cancer Treatment & Women Health: Market Access & Cost Concerns

http://pharmaceuticalintelligence.com/2013/02/10/global-burden-of-cancer-treatment-women-health-market-access-cost-concerns/

Lev-Ari, A. 11/21/2012, Response to Multiple Cancer Drugs through Regulation of TGF- Receptor Signaling: a MED12 Control

http://pharmaceuticalintelligence.com/2012/11/21/response-to-multiple-cancer-drugs-through-regulation-of-tgf-%CE%B2-receptor-signaling-a-med12-control/

Lev-Ari, A. 10/1/2012, “Increased risks of obesity and cancer, Decreased risk of type 2 diabetes: The role of Tumor-suppressor phosphatase and tensin homologue (PTEN)”

http://pharmaceuticalintelligence.com/2012/10/01/increased-risks-of-obesity-and-cancer-decreased-risk-of-type-2-diabetes-the-role-of-tumor-suppressor-phosphatase-and-tensin-homologue-pten/

Lev-Ari, A. 12/8/2012, Aspirin a Day Tied to Lower Cancer Mortality

http://pharmaceuticalintelligence.com/2012/08/11/1796/

Lev-Ari, A. 2/5/2013, Winning Over Cancer Progression: New Oncology Drugs to Suppress Passengers Mutations vs. Driver Mutations

http://pharmaceuticalintelligence.com/2013/02/05/winning-over-cancer-progression-new-oncology-drugs-to-suppress-driver-mutations-vs-passengers-mutations/

Lev-Ari, A. 4/22/2013, “Molecular Profiling in Cancer Immunotherapy: Debraj Guha Thakurta, PhD”

http://pharmaceuticalintelligence.com/2013/04/22/molecular-profiling-in-cancer-immunotherapy/

Lev-Ari, A. 5/16/2013, “Immunomodulatory Therapeutic Antibodies for Cancer, August 13-15, 2013 – Boston, MA – Final Agenda”

http://pharmaceuticalintelligence.com/2013/05/16/immunomodulatory-therapeutic-antibodies-for-cancer-august-13-15-2013-boston-ma-final-agenda/

Lev-Ari, A. 11/14/2012, GSK for Personalized Medicine using Cancer Drugs needs Alacris systems biology model to determine the in silico effect of the inhibitor in its “virtual clinical trial”

http://pharmaceuticalintelligence.com/2012/11/14/gsk-for-personalized-medicine-using-cancer-drugs-needs-alacris-systems-biology-model-to-determine-the-in-silico-effect-of-the-inhibitor-in-its-virtual-clinical-trial/

Lev-Ari, A. 10/16/2012, Personalized Pancreatic Cancer Treatment Option

http://pharmaceuticalintelligence.com/2012/10/16/personalized-pancreatic-cancer-treatment-option/

Lev-Ari, A. 7/10/12, Pfizer’s Kidney Cancer Drug Sutent Effectively caused REMISSION to Adult Acute Lymphoblastic Leukemia (ALL)

http://pharmaceuticalintelligence.com/2012/07/10/pfizers-kidney-cancer-drug-sutent-effectively-caused-remission-to-adult-acute-lymphoblastic-leukemia-all/

Lev-Ari, A. 7/9/2012, Sunitinib brings Adult Acute Lymphoblastic Leukemia (ALL) to Remission – RNA Sequencing – FLT3 Receptor Blockade

http://pharmaceuticalintelligence.com/2012/07/09/sunitinib-brings-adult-all-to-remission-rna-sequencing/

Lev-Ari, A. 7/10/2012, REMISSION to Adult Acute Lymphoblastic Leukemia (ALL): Pfizer’s Sutent blocks FLT3 Gene Receptors

http://pharmaceuticalintelligence.com/2012/07/10/remission-to-adult-acute-lymphoblastic-leukemia-all-pfizers-sutent-blocks-flt3-gene-receptors/

Genomics and Cancer

Lev-Ari, A. 9/18/2012, Head and Neck Cancer Studies Suggest Alternative Markers More Prognostically Useful than HPV DNA Testing

http://pharmaceuticalintelligence.com/2012/09/18/head-and-neck-cancer-studies-suggest-alternative-markers-more-prognostically-useful-than-hpv-dna-testing/

Lev-Ari, A. 10/24/2012, Pancreatic cancer genomes: Axon guidance pathway genes – aberrations revealed

http://pharmaceuticalintelligence.com/2012/10/24/pancreatic-cancer-genomes-axon-guidance-pathway-genes-aberrations-revealed/

Lev-Ari, A. 10/24/2012, Biomarker tool development for Early Diagnosis of Pancreatic Cancer: Van Andel Institute and Emory University

http://pharmaceuticalintelligence.com/2012/10/24/biomarker-tool-development-for-early-diagnosis-of-pancreatic-cancer-van-andel-institute-and-emory-university/

Lev-Ari, A. 4/22/2013, “DNA Methultransferases – Implications to Epigenetic Regulation and Cancer Therapy Targeting: James Shen, PhD”

http://pharmaceuticalintelligence.com/2013/04/22/dna-methultransferases-implications-to-epigenetic-regulation-and-cancer-therapy-targeting-james-shen-phd/

Lev-Ari, A. 4/22/2013, “Genotype-based Analysis for Cancer Therapy using Large-scale Data Modeling: Nayoung Kim, PhD(c)”

http://pharmaceuticalintelligence.com/2013/04/22/genotype-based-analysis-for-cancer-therapy-using-large-scale-data-modeling-nayoung-kim-phdc/

Lev-Ari, A. 4/21/2013, Cancer Genomic Precision Therapy: Digitized Tumor’s Genome (WGSA) Compared with Genome-native Germ Line: Flash-frozen specimen and Formalin-fixed paraffin-embedded Specimen Needed

http://pharmaceuticalintelligence.com/2013/04/21/cancer-genomic-precision-therapy-digitized-tumors-genome-wgsa-compared-with-genome-native-germ-line-flash-frozen-specimen-and-formalin-fixed-paraffin-embedded-specimen-needed/

Lev-Ari, A. 1/13/2013, LEADERS in Genome Sequencing of Genetic Mutations for Therapeutic Drug Selection in Cancer Personalized Treatment: Part 2

http://pharmaceuticalintelligence.com/2013/01/13/leaders-in-genome-sequencing-of-genetic-mutations-for-therapeutic-drug-selection-in-cancer-personalized-treatment-part-2/

Lev-Ari, A. 1/10/2013, Inspiration From Dr. Maureen Cronin’s Achievements in Applying Genomic Sequencing to Cancer Diagnostics

http://pharmaceuticalintelligence.com/2013/01/10/inspiration-from-dr-maureen-cronins-achievements-in-applying-genomic-sequencing-to-cancer-diagnostics/

Lev-Ari, A. 11/1/2012, arrayMap: Genomic Feature Mining of Cancer Entities of Copy Number Abnormalities (CNAs) Data

http://pharmaceuticalintelligence.com/2012/11/01/arraymap-genomic-feature-mining-of-cancer-entities-of-copy-number-abnormalities-cnas-data/

Lev-Ari, A. 10/29/2012, Cancer Genomics – Leading the Way by Cancer Genomics Program at UC Santa Cruz

http://pharmaceuticalintelligence.com/2012/10/29/cancer-genomics-leading-the-way-by-cancer-genomics-program-at-uc-santa-cruz/

Lev-Ari, A. 9/10/2012, Comprehensive Genomic Characterization of Squamous Cell Lung Cancers

http://pharmaceuticalintelligence.com/2012/09/10/comprehensive-genomic-characterization-of-squamous-cell-lung-cancers/

Lev-Ari, A. 5/21/2013, “Prostate Cancer Molecular Diagnostic Market – the Players are: SRI Int’l, Genomic Health w/Cleveland Clinic, Myriad Genetics w/UCSF, GenomeDx and BioTheranostics”

http://pharmaceuticalintelligence.com/2013/05/21/prostate-cancer-molecular-diagnostic-market-the-players-are-sri-intl-genomic-health-wcleveland-clinic-myriad-genetics-wucsf-genomedx-and-biotheranostics/

Lev-Ari, A. 5/16/2013, “A Blood Test to Identify Aggressive Prostate Cancer: a Discovery @ SRI International, Menlo Park, CA”

http://pharmaceuticalintelligence.com/2013/05/16/a-blood-test-to-identify-aggressive-prostate-cancer-a-discovery-sri-international-menlo-park-ca/

Lev-Ari, A. 5/20/2013, Salivary Gland Cancer – Adenoid Cystic Carcinoma: Mutation Patterns: Exome- and Genome-Sequencing @ Memorial Sloan-Kettering Cancer Center

http://pharmaceuticalintelligence.com/2013/05/20/salivary-gland-cancer-adenoid-cystic-carcinoma-mutation-patterns-exome-and-genome-sequencing-memorial-sloan-kettering-cancer-center/

Cancer Research by Cancer Type

Breast

Lev-Ari, A. 7/3/2013, MIT Scientists Identified Gene that Controls Aggressiveness in Breast Cancer Cells

http://pharmaceuticalintelligence.com/2013/07/03/mit-scientists-identified-gene-that-controls-aggressiveness-in-breast-cancer-cells/

Lev-Ari, A. 4/23/2013, Tamoxifen’s Effectiveness: Decrease in Tissue Density by Mammography – 50% Lower Risk of Dying from Breast Cancer

http://pharmaceuticalintelligence.com/2013/04/23/tamoxifens-effectiveness-decrease-in-tissue-density-by-mammography-50-lower-risk-of-dying-from-breast-cancer/

Lev-Ari, A. 1/17/2013, Mechanism involved in Breast Cancer Cell Growth: Function in Early Detection & Treatment

http://pharmaceuticalintelligence.com/2013/01/17/mechanism-involved-in-breast-cancer-cell-growth-function-in-early-detection-treatment/

Lev-Ari, A. 8/14/2012, Missing Gene may drive more than a quarter of Breast Cancers

http://pharmaceuticalintelligence.com/2012/08/14/missing-gene-may-drive-more-than-a-quarter-of-breast-cancers/

Breast/Ovarian

Lev-Ari, A. 5/20/2013, “Testing for Multiple Genetic Mutations via NGS for Patients: Very Strong Family History of Breast & Ovarian Cancer, Diagnosed at Young Ages, & Negative on BRCA Test”

http://pharmaceuticalintelligence.com/2013/05/20/testing-for-multiple-genetic-mutations-via-ngs-for-patients-very-strong-family-history-of-breast-ovarian-cancer-diagnosed-at-young-ages-negative-on-brca-test/

Breast/Personalized Medicine

Lev-Ari, A. 12/24/2014, Breast Cancer: Genomic profiling to predict Survival: Combination of Histopathology and Gene Expression Analysis

http://pharmaceuticalintelligence.com/2012/12/24/breast-cancer-genomic-profiling-to-predict-survival-combination-of-histopathology-and-gene-expression-analysis/

Colon

Lev-Ari, A. 11/28/2012, PIK3CA mutation in Colorectal Cancer may serve as a Predictive Molecular Biomarker for adjuvant Aspirin therapy

http://pharmaceuticalintelligence.com/2012/11/28/pik3ca-mutation-in-colorectal-cancer-may-serve-as-a-predictive-molecular-biomarker-for-adjuvant-aspirin-therapy/

Epigenetics

Lev-Ari, A. 4/12/2013, Critical Gene in Calcium Reabsorption: Variants in the KCNJ and SLC12A1 genes – Calcium Intake and Cancer Protection

http://pharmaceuticalintelligence.com/2013/04/12/critical-gene-in-calcium-reabsorption-variants-in-the-kcnj-and-slc12a1-genes-calcium-intake-and-cancer-protection/

Gastric

Lev-Ari, A. 10/17/2012, Stomach Cancer Subtypes Methylation-based identified by Singapore-Led Team

http://pharmaceuticalintelligence.com/2012/10/17/stomach-cancer-subtypes-methylation-based-identified-by-singapore-led-team/

Gastric/Personalized Medicine

Lev-Ari, A. 12/24/2012, Gastric Cancer: Whole-genome reconstruction and mutational signatures

http://pharmaceuticalintelligence.com/2012/12/24/gastric-cancer-whole-genome-reconstruction-and-mutational-signatures-2/

Skin Cancer

Lev-Ari, A. 4/24/2013, Association between Non-melanoma Skin Cancer and subsequent Primary Cancers in White Population

http://pharmaceuticalintelligence.com/2013/04/24/association-between-non-melanoma-skin-cancer-and-subsequent-primary-cancers-in-white-population/

Prostate Cancer

Lev-Ari, A. 2/14/13, Prostate Cancer: Androgen-driven “Pathomechanism” in Early-onset Forms of the Disease

http://pharmaceuticalintelligence.com/2013/02/14/prostate-cancer-androgen-driven-pathomechanism-in-early-onset-forms-of-the-disease/

Lev-Ari, A. 7/31/2012, “Prostate Cancers Plunged After USPSTF Guidance, Will It Happen Again?”

http://pharmaceuticalintelligence.com/2012/07/31/prostate-cancers-plunged-after-uspstf-guidance-will-it-happen-again/

Head & Neck

Lev-Ari, A. 1030/2012, Acoustic Neuroma, Neurinoma or Vestibular Schwannoma: Treatment Options

http://pharmaceuticalintelligence.com/2012/10/30/acoustic-neuroma-neurinoma-or-vestibular-schwannoma-treatment-options/

Lev-Ari, A. 10/30/2012, Clinical Trials on Schwannoma & Benign Intracranial Tumors Radiosurgery Treatment

http://pharmaceuticalintelligence.com/2012/10/30/clinical-trials-on-schwannoma-benign-intracranial-tumors-radiosurgery-treatment/

Lev-Ari, A. 10/15/2012, Facial Nerve, Intracanalicular Meningiomas, Vestibular Schwannomas: Surgical Planning

http://pharmaceuticalintelligence.com/2012/10/15/facial-nerve-intracanalicular-meningiomas-vestibular-schwannomas-surgical-planning/

Cancer and the Human Heart – Correlation between Cancer and Cardiovascular Diseases

o Causes

Lev-Ari, A. 1/8/2014, Reuben Shaw, Ph.D., a geneticist and researcher at the Salk Institute: Metabolism Influences Cancer

http://pharmaceuticalintelligence.com/2014/01/08/reuben-shaw-ph-d-a-geneticist-and-researcher-at-the-salk-institute-metabolism-influences-cancer/

Lev-Ari, A. 1/8/2014, Heart Tumors: Etiology and Classification

http://pharmaceuticalintelligence.com/2014/01/08/heart-tumors-etiology-and-classification/

o Biomarkrs

Lev-Ari, A. 1/15/2014, Cancer Symptom Science: On the Mechanisms underlying the Expression of Cancer-related Symptoms

http://pharmaceuticalintelligence.com/2014/01/15/cancer-symptom-science-on-the-mechanisms-underlying-the-expression-of-cancer-related-symptoms/

o Therapies

Lev-Ari, A. 1/8/2014, Cardio-oncology and Onco-Cardiology Programs: Treatments for Cancer Patients with a History of Cardiovascular Disease

http://pharmaceuticalintelligence.com/2014/01/08/cardio-oncology-and-onco-cardiology-programs-treatments-for-cancer-patients-with-a-history-of-cardiovascular-disease/

Lev-Ari, A. 1/8/2014, Radiation and Chemotherapy Therapy: The Pharmacological Risk for Developing Cardiovascular Disease

http://pharmaceuticalintelligence.com/2014/01/08/20316/

Lev-Ari, A. 1/8/2014, 3rd Annual Canadian Cardiac Oncology Network Conference, June 20 – 21, 2013, Ottawa Convention Centre

http://pharmaceuticalintelligence.com/2014/01/08/3rd-annual-canadian-cardiac-oncology-network-conference-june-20-21-2013-ottawa-convention-centre/

Read Full Post »

Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA

Posted in Affordable Care Act, Bio Instrumentation in Experimental Life Sciences Research, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cell Biology, Signaling & Cell Circuits, Cerebrovascular and Neurodegenerative Diseases, Chemical Biology and its relations to Metabolic Disease, Circulating Progenitor Cells, Computational Biology/Systems and Bioinformatics, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Drug Delivery Platform Technology, FDA Regulatory Affairs, Genome Biology, Intellectual Property, Innovations, Commercialization, Investment in technological breakthrough, International Global Work in Pharmaceutical, Interviews with Scientific Leaders, Medical and Population Genetics, Medical Devices R&D Investment, Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, Molecular Genetics & Pharmaceutical, Personalized and Precision Medicine & Genomic Research, Pharmaceutical Analytics, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Investment, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, Translational Science on April 7, 2014| Leave a Comment »

Methodology for Conference Coverage using Social Media:

2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA

Curator: Aviva Lev-Ari, PhD, RN

e-mail: avivalev-ari@alum.berkeley.edu

Article ID #126: Methodology for Conference Coverage using Social Media: 2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA. Published on 4/7/2014

WordCloud Image Produced by Adam Tubman

This article has three Parts:

Part One: Conference Agenda: Intellectual Property of MassBio

https://twitter.com/search?q=%40massbio&src=rela

https://twitter.com/search?q=%23Impact2020&src=hash

https://twitter.com/search?q=%23AM2014&src=hash

http://www.massbio.org/events/calendar/2534-around_the_world_in_120_days_europe_101-/event_detail

Part Two: Conference Content Acquisition in REALTIME

Content: Spoken Words – IP of the Speakers
Electronic Recording of the Curation of the Spoken Words – IP of Leaders in Pharmaceutical Business Intelligence

Part Three: Social Media in Use of Information Dissemination

3.1 Our Tweets @ pharma_BI on www.twitter.com

3.2 REALTIME Posting to 53 LinkedIn BioTech Groups

3.3 FaceBook Coverage of the Event

https://www.facebook.com/LeadersInPharmaceuticalBusinessIntelligence

3.4 Our Open Access Online Scientific JOURNAL @ http://pharmaceuticalintelligence.com

3.5 GENOMICS related articles in the JOURNAL @ http://pharmaceuticalintelligence.com

3.6 e-Books on Genomics our BioMed e-Series

Part One

CONFERENCE AGENDA

MassBio Annual Meeting 2014
Thursday, April 3 – Friday, April 4 2014

Royal Sonesta Hotel, 40 Edwin Land Blvd, Cambridge, MA

FEATURING REMARKS FROM

Senator Elizabeth Warren
Margaret Hamburg, Commissioner, Food & Drug Administration
Dr. Flemming Ornskov, President & CEO, Shire
Dr. George Scangos, CEO, Biogen Idec
Brad Margus, CEO, Genome Bridge

Thursday, April 3

8:00 am – 9:00 am Breakfast and Poster Presentation

9:00 am – 9:30 am Welcome Remarks, Overview of Meeting, and MassBio Board Elections

9:30 am – 10:15 am Opening Keynote: Brad Margus, CEO of Genome Bridge

10:15 am – 10:30 am Coffee Break

10:30 am – 11:30 am Breakout Sessions

Business Track: The Image Problem of the BioPharma Industry

Panelists:

Lisa Adler, Vice President, Corporate Communications, Millennium: The Takeda Oncology Company
Maria Cantor, Senior Vice President, Corporate Affairs and Human Resources, ARIAD
Karen Carolonza, Principal, Strategy, Green Room Communications
Lori Gorski, Director, Corporate Communications, Genzyme

Moderator:

Luke Timmerman, Biotechnology Journalist

Science Track: Clinical Trial Trends

Panelists:

Neil Bodick, Chief Medical Officer & Co-Founder, Flexion Therapeutics
Marc Foster, Co-Founder & COO, Transparency Life Sciences
Amy O’Donnell, Executive Medical Director, Medical and Scientific Affairs, inVentiv Health Clinical
Richard Peters, Vice President & Division Medical Officer, Sanofi Oncology

Moderator:

Mark de Rosch, Vice President of Regulatory Drugs/Biologics and Head of US Operations, Voisin Consulting Life Sciences
11:45 am – 1:30 pm Awards Luncheon

11:45 am – 12:00 pm Awards Luncheon: Lunch is served

12:00 pm – 12:20 pm Leading Impact Award

12:20 pm – 12:45pm 2013 Joshua Boger Innovative School of the Year Award

12:45 pm – 1:30 pm Henri A. Termeer Innovative Leadership Award

1:30 pm – 2:15 pm Conference Wide Panel: Impact 2020 Overview

Panelists:

Glenn Batchelder, Founder & Board Member, Civitas Therapeutics
Katrine Bosley, Entrepreneur-in-residence, Broad Institute
Skip Irving, Partner and Managing Director, Health Advances
Terry McGuire, Co-Founder & General Partner, Polaris Partners

Moderator:

Rob Weisman, Healthcare Business Writer, The Boston Globe

2:15 pm – 3:15 pm Breakout Sessions

Business Track: Beg, Borrow & Crowdsource? Innovative Ways to Fund Your Early Stage Company

Panelists:

Alex Fair, Co-Founder and CEO, MedStartR
Barbara Fox, CEO & Founder, Avaxia Biologlics, Inc.
Dan Lilly, Government Sales Advisor, Massachusetts Small Business Development Center
Andrew Lo, Professor and Director, MIT Laboratory for Financial Engineering
Brock Reeve, Portfolio Manager, Poliwogg

Moderator:

Margaret Anderson, Executive Director, FasterCures

Science Track: Challenges to Managing Big Data

Panelists:

Bill Crown, Chief Scientific Officer, Optum Labs
Anil Jain, Chief Medical Information Officer, Explorys, Inc.
Iya Khalil, Executive Vice President and Co-Founder, GNS Healthcare
Peter Neumann, Director, Center for the Evaluation of Value and Risk in Health at the Institute for Clinical Research and Health Policy Studies at Tufts Medical Center

Moderator:

Jeff Elton, Managing Director of Life Sciences, Accenture

3:15 pm – 3:30 pm Afternoon Break

3:30 pm – 4:30 pm Breakout Sessions

Business Track: Winning Strategies in Business and Corporate Development:

What are They and How Can We Learn From Them?

Panelists:

Tariq Kassum, Vice President, Business Development and Strategy, Millennium: The Takeda Oncology Company
Tomas Landh, Director, Strategy and Innovation Sourcing, Diabetes, Novo Nordisk
Jason Rhodes, President & CFO, Epizyme

Moderator:

Jay Mohr, Managing Director and Co-Founder, Locust Walk Partners

Science Track: The Second Coming of Molecular Therapies

Panelists:

Philip Astley-Sparke, President US, uniQure
Stéphane Bancel, President and Founding Chief Executive Officer, Moderna
Kevin Bitterman, Interim CEO, Editas Medicine and Principal, Polaris Partners
Nick Leschly, chief bluebird, bluebird bio

Moderator:

Fred Ledley, Professor and Director at Center for Integration of Science and Industry, Bentley University

4:30 – 6:30 pm Reception

Friday, April 4

8:00am – 8:30 am Breakfast

8:30 – 9:30 am Breakout Sessions

Business Track: Addressing Opportunity Cost When We Focus on Rare Disease

Panelists:

Cristina Csimma, CEO, Cydan Development
Laurence Reid, Senior Vice President and Chief Business Officer, Alnylam
Rajeev Shah, Partner, RA Capital Management
Andre Turenne, Vice President & Head of Strategy and Business Development, Genzyme

Moderator:

Barry Werth, Author

Science Track: Mobile Technology and 3D Printing: Technologies Gaining Traction in Biotech and Pharma

Panelists:

Scott DeFelice, President, Oxford Performance Materials
David Kolesky, PhD Candidate, Lewis Research Group, Harvard University
Jacques Kpodonu, Cardiac Surgeon, Beth Israel Deaconess Medical Center
Ravi Kuppuraj, CTO & Co-Founder, InfoBionic

Moderator:

Navjot Singh, Director, McKinsey & Company
9:45 am – 10:45 am Breakout Sessions

Business Track: Converging Relationships Among Biotech, Pharma, Investors, and Academia

Panelists:

Jane Amara, Director (interim),Technology & Innovation Development Office, Boston Children’s Hospital
Kathy Bowdish, Vice President Global R&D and Head of Sunrise
Judith Dunn, Global Head of pRED Clinical Development, Hoffmann-La Roche
Ben Thorner, Associate Vice President, Head of Business Development and Licensing, Boston Innovation Hub, Merck Research Laboratories
James Tobin, Vice President, Cardiovascular and Scientific Innovation, Johnson & Johnson

Moderator:

Jonathan Gertler, Managing Partner and CEO, Back Bay Life Sciences Advisors

Science Track: New Approaches to Treatments for Neurological Disease

Panelists:

Zaven Kaprielian, Director of Neuroscience Research, Amgen
Jeffrey Nye, Vice President Neuroscience Innovation and Scientific Partnership Strategy, Janssen Research and Development, LLC, Johnson and Johnson Innovation
Mark Perrin, CEO, InVivo Therapeutics

Moderator:

Dennis Selkoe, Co-Director, Center for Neurologic Diseases, Brigham and Women’s Hospital at the Harvard Institutes of Medicine

10:45 am – 11:00 am Coffee Break

11:00 am – 12:00 pm Conference Wide Panel: Value Cost Effectiveness: Implications of the Changing Landscape in Reimbursement and Regulations

Panelists:

Chris Coburn, Vice President, Innovation, Partners HealthCare
Geoff MacKay,President & CEO, Organogenesis
Christina Severin, President & CEO, Beth Israel Deaconess Care Organization

12:00 pm – 12:30pm Remarks by FDA Commissioner Margaret Hamburg

Introduction by Senator Elizabeth Warren

12:30 pm – 12:45 pm Lunch is Served

12:45 pm – 1:30 pm Closing Keynote: Flemming Ornskov, CEO of Shire

1:30 pm – 2:00 pm Dessert Buffet in the Ballroom Foyer

SOURCE

http://www.massbio.org/events/calendar/2302-massbio_annual_meeting_2014/event_detail/544

Part Two:

Conference Content Acquisition in REALTIME

Content: Spoken Words – IP of the Speakers
Electronic Recording of the Curation of the Spoken Words – IP of Leaders in Pharmaceutical Business Intelligence

TODAY – 9:30 am – 10:15 am Opening Keynote: Brad Margus, CEO of Genome Bridge – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-930-am-1015-am-opening-keynote-brad-margus-ceo-of-genome-bridge-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

TODAY – 10:30 am – 11:30 am Business Track: The Image Problem of the BioPharma Industry – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-1030-am-1130-am-business-track-the-image-problem-of-the-biopharma-industry-bridge-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

TODAY – 11:45 am – 1:30 pm Awards Luncheon – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-1145-am-130-pm-awards-luncheon-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

TODAY –1:30 pm –2:15 pm Conference Wide Panel: Impact 2020 Overview – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-130-pm-215-pm-conference-wide-panel-impact-2020-overview-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

TODAY – 2:15 pm –3:15 pm Science Track: Challenges to Managing Big Data – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-215-pm-315-pm-science-track-challenges-to-managing-big-data-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

TODAY – 3:30 pm –4:30 pm Business Track: Winning Strategies in Business and Corporate Development: What are They and How Can We Learn From Them? – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/03/today-330-pm-430-pm-business-track-winning-strategies-in-business-and-corporate-development-what-are-they-and-how-can-we-learn-from-them-massbio-annual-meeting-2014-royal-so/

Friday, April 4 8:30 am – 9:30 am Science Track: Mobile Technology and 3D Printing: Technologies Gaining Traction in Biotech and Pharma – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/04/friday-april-4-830-am-930-am-science-track-mobile-technology-and-3d-printing-technologies-gaining-traction-in-biotech-and-pharma-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

Friday, April 4 9:45 am – 10:45 am Business Track: Converging Relationships Among Biotech, Pharma, Investors, and Academia- MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/04/friday-april-4-945-am-1045-am-business-track-converging-relationships-among-biotech-pharma-investors-and-academia-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

Friday, 11:00 am – 12:00 pm Conference Wide Panel: Value Cost Effectiveness: Implications of the Changing Landscape in Reimbursement and Regulations – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/04/friday-1100-am-1200-pm-conference-wide-panel-value-cost-effectiveness-implications-of-the-changing-landscape-in-reimbursement-and-regulations-massbio-annual-meeting-2014-royal-sonesta/

Friday, April 4, 12:45 pm – 1:30 pm Closing Keynote: Flemming Ornskov, CEO of Shire – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA

http://pharmaceuticalintelligence.com/2014/04/04/friday-april-4-1245-pm-130-pm-closing-keynote-flemming-ornskov-ceo-of-shire-massbio-annual-meeting-2014-royal-sonesta-hotel-cambridge-ma/

Part Three:

Social Media in Use of Information Dissemination

3.1 Our Tweets

@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4, 12:45 pm – 1:30 pm Closing Keynote: Flemming Ornskov, CEO of Shire – MassBio Annual Meeting 2014, R…http://lnkd.in/dkEpNJm

@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4, 12:45 pm – 1:30 pm Closing Keynote: Flemming Ornskov, CEO of Shire – MassBio… http://fb.me/2NahP8tfv
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4, 12:45 pm – 1:30 pm Closing Keynote: Flemming Ornskov, CEO of Shire – MassBio Annual Meeting 2014,… http://wp.me/p2kEDv-5FK
@pharma_BI ‏@Pharma_BI Apr 4

Friday 11:00 am – 12:00 pm Conference Wide Panel: Value Cost Effectiveness: Implications of the Changing Landscape i…http://lnkd.in/dbR2Q23
@pharma_BI ‏@Pharma_BI Apr 4

Friday 11:00 am – 12:00 pm Conference Wide Panel: Value Cost Effectiveness: Implications of the… http://fb.me/6Iut9RIr7
@pharma_BI ‏@Pharma_BI Apr 4

Friday 11:00 am – 12:00 pm Conference Wide Panel: Value Cost Effectiveness: Implications of the Changing Landscape… http://wp.me/p2kEDv-5FC
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 9:45 am – 10:45 am Business Track: Converging Relationships Among Biotech, Pharma, Investors, and Ac…http://lnkd.in/dWm8Vd7
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 9:45 am – 10:45 am Business Track: Converging Relationships Among Biotech,… http://fb.me/2A24u7vds
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 9:45 am – 10:45 am Business Track: Converging Relationships Among Biotech, Pharma, Investors, and… http://wp.me/p2kEDv-5Ft
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 8:30 am- 9:30 am Science Track: Mobile Technology and 3D Printing: Technologies Gaining Traction in …http://lnkd.in/d87iquJ
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 8:30 am- 9:30 am Science Track: Mobile Technology and 3D Printing: Technologies… http://fb.me/1iupazGjg
@pharma_BI ‏@Pharma_BI Apr 4

Friday, April 4 8:30 am- 9:30 am Science Track: Mobile Technology and 3D Printing: Technologies Gaining Traction in… http://wp.me/p2kEDv-5Fp
@pharma_BI ‏@Pharma_BI Apr 4

7 Ways To Boost Your Creativity http://fb.me/3h4PiHQVH
@pharma_BI ‏@Pharma_BI Apr 4

US patent office stops Google trademarking ‘Glass’ http://lnkd.in/d_FUTTk
Retweeted by @pharma_BI

Genentech ‏@genentech Apr 3

Our scientists dev clinically-relevant mouse model to test spontaneous metastatic lesions in CRC | @NatureComms http://ow.ly/vmJm1
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 3:30 pm –4:30 pm Business Track: Winning Strategies in Business and Corporate Development: What are They and…http://lnkd.in/dwYTdn6
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 3:30 pm –4:30 pm Business Track: Winning Strategies in Business and Corporate… http://fb.me/3lyo10zgN
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 3:30 pm –4:30 pm Business Track: Winning Strategies in Business and Corporate Development: What are They… http://wp.me/p2kEDv-5Fh
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 2:15 pm –3:15 pm Science Track: Challenges to Managing Big Data – MassBio Annual Meeting 20… http://wp.me/p2kEDv-5Ff via @Pharma_BI
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 2:15 pm –3:15 pm Science Track: Challenges to Managing Big Data – MassBio Annual Meeting 2014, Royal Sonesta…http://lnkd.in/dVVVs8g
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 2:15 pm –3:15 pm Science Track: Challenges to Managing Big Data – MassBio Annual Meeting 2014, Royal… http://wp.me/p2kEDv-5Ff
@pharma_BI ‏@Pharma_BI Apr 3

TODAY –1:30 pm –2:15 pm Conference Wide Panel: Impact 2020 Overview – MassBio Annual Meeting 2014, Royal Sonesta Hot…http://lnkd.in/dCeTerz
@pharma_BI ‏@Pharma_BI Apr 3

TODAY –1:30 pm –2:15 pm Conference Wide Panel: Impact 2020 Overview – MassBio Annual Meeting 2014, … http://wp.me/p2kEDv-5F9 via @Pharma_BI
@pharma_BI ‏@Pharma_BI Apr 3

TODAY –1:30 pm –2:15 pm Conference Wide Panel: Impact 2020 Overview – MassBio Annual Meeting… http://fb.me/D1sZ0ABP
@pharma_BI ‏@Pharma_BI Apr 3

TODAY –1:30 pm –2:15 pm Conference Wide Panel: Impact 2020 Overview – MassBio Annual Meeting 2014, Royal Sonesta… http://wp.me/p2kEDv-5F9
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 11:45 am – 1:30 pm Awards Luncheon – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 11:45 am – 1:30 pm Awards Luncheon – MassBio Annual Meeting 2014, Royal Sonesta Hotel,…
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 11:45 am – 1:30 pm Awards Luncheon – MassBio Annual Meeting 2014, Royal Sonesta Hotel, Cambridge, MA http://wp.me/p2kEDv-5F7
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 10:30 am – 11:30 am Business Track: The Image Problem of the BioPharma Industry – Bridge – MassBio Annual Me…http://lnkd.in/dp4w2yT
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 10:30 am – 11:30 am Business Track: The Image Problem of the BioPharma Industry – Bridge… http://fb.me/6w43w6q3T
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 10:30 am – 11:30 am Business Track: The Image Problem of the BioPharma Industry – Bridge – MassBio Annual… http://wp.me/p2kEDv-5F0
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 9:30 am – 10:15 am Opening Keynote: Brad Margus, CEO of Genome Bridge – MassBio Annual Meeting 2014, Royal S…http://lnkd.in/d-wKpbS
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 9:30 am – 10:15 am Opening Keynote: Brad Margus, CEO of Genome Bridge – MassBio Annual… http://fb.me/2zBbAscQc
@pharma_BI ‏@Pharma_BI Apr 3

TODAY – 9:30 am – 10:15 am Opening Keynote: Brad Margus, CEO of Genome Bridge – MassBio Annual Meeting 2014, Royal… http://wp.me/p2kEDv-5EY
@pharma_BI ‏@Pharma_BI Apr 3

2014 MassBio Annual Meeting 4/3 – 4/4 2014, Royal Sonesta Hotel, Cambridge, MA http://fb.me/6qpvQBHER

3.2 REALTIME Posting to 53 LinkedIn BioTech Groups

3.3 FaceBook Coverage of the Event

https://www.facebook.com/LeadersInPharmaceuticalBusinessIntelligence

3.4 Our Open Access Online Scientific Journal

http://pharmaceuticalintelligence.com

3.5 GENOMICS related articles in the JOURNAL

Cardiovascular Pharmacogenomics – 134 articles
Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics – 55 articles
Nutrigenomics – 43 articles
Pharmacogenomics – 88 articles
Genomic Testing: Methodology for Diagnosis – 241 articles
Personalized Medicine & Genomic Research – 390 articles
Genome Biology – 421 articles

Series B: Frontiers in Genomics Research

Content Consultant: Larry H Bernstein, MD, FCAP

Genomics Orientations for Individualized Medicine

Volume One

Image Collage by SJ WIlliams, PhD, Google Images in Assembly

Larry H Bernstein, MD, FCAP, Senior Editor

Triplex Medical Science, Trumbull, CT

Larry.bernstein@gmail.com

and
Stephen J. Williams, PhD, Editor

Leaders in Pharmaceutical Business Intelligence, Philadelphia

sjwilliamspa@comcast.net

and

Aviva Lev-Ari, PhD, RN, Editor

Editor-in-Chief BioMed E-Book Series

Leaders in Pharmaceutical Business Intelligence, Boston

avivalev-ari@alum.berkeley.edu

Volume Two:
Genomics Methodologies: NGS, BioInformatics & Simulations and the Genome Ontology

2015

Volume Three:
Five Leading Genomics Research Centers in the US

2015

Read Full Post »

Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

Posted in Cell Biology, Signaling & Cell Circuits, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, HTN, Human Immune System in Health and in Disease, Human Sensation and Cellular Transduction: Physiology and Therapeutics, Innovation in Immunology Diagnostics, Interviews with Scientific Leaders, Ionic Transporters Na+, K, Medical and Population Genetics, Molecular Genetics & Pharmaceutical, Na-K transport, Na-K-ATPase, Nephrology, Nephrology & Regenerative medicine, Neurohumoral Transmission, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Pre-Clinical Animal Model Development, Signaling, Systemic Inflammatory Response Related Disorders, Water Transporters on March 3, 2014| Leave a Comment »

Richard Lifton, MD, PhD of Yale University & Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension

Curator: Aviva Lev-Ari, PhD, RN

Article ID #118: Richard Lifton, MD, PhD of Yale University and Howard Hughes Medical Institute: Recipient of 2014 Breakthrough Prizes Awarded in Life Sciences for the Discovery of Genes and Biochemical Mechanisms that cause Hypertension. Published on 3/3/2014

WordCloud Image Produced by Adam Tubman

Yale’s Lifton receives $3 million science prize at gala Silicon Valley ceremony

Friday, December 13, 2013

Bill Hathaway / 203-432-1322

Read this article on YaleNews

Richard Lifton, Sterling Professor of Genetics and chair of the Department of Genetics, has received a $3 million Breakthrough Prize in Life Sciences, created by top Silicon Valley entrepreneurs.

Lifton was one of eight scientists honored Dec. 12 with $21 million in prizes at gala ceremonies hosted by actor Kevin Spacey in Mountain View, California. Celebrities — including Conan O’Brien, Glenn Close, Rob Lowe, and Michael C. Hall — handed out awards to six winners of the life sciences prizes and two co-winners of the Breakthrough Prize in Fundamental Physics.

“Scientists should be celebrated as heroes, and we are honored to be part of today’s celebration,” said Google co-founder Sergey Brin and his wife, biologist and entrepreneur Anne Wojcicki, two of the event’s sponsors.

Lifton, who is also an investigator for the Howard Hughes Medical Institute, was recognized for his pioneering work to identify the genetic and biochemical underpinnings of hypertension, a disease that affects more than 1 billion people worldwide and that contributes to 17 million deaths annually from heart attack and stroke. Lifton and his colleagues identified patients around the world with exceptionally high or low blood pressure due to single gene mutations. They identified the mutated genes and established their role in salt reabsorption by the kidney and regulation of blood pressure. The work gave scientific rationale to limit dietary salt intake and suggested rational combinations of antihypertensive medications and development of new therapies.

Other sponsors of the event are Chinese internet entrepreneur Jack Ma and Cathy Zhang; Russian entrepreneur and venture capitalist Yuri Milner and his wife, Julia Milner; and Facebook founder Mark Zuckerberg and Priscilla Chan.

At the end of the ceremonies, which will be televised on the Science Channel at 9 p.m. on Jan. 27, Milner and Zuckerberg announced the creation of a $3 million Breakthrough Prize in Mathematics that will be awarded next year.

Additional information on the prizes can be found atwww.breakthroughprizeinlifesciences.org or www.fundamentalphysicsprize.org.

SOURCE

http://www.bizjournals.com/sanfrancisco/prnewswire/press_releases/California/2013/12/13/NY33121

THE DISCOVERY

Laliotis MD, Zhang J, Volkman HM, Kahle KT, Hoffmann, KE, Toka HR, Nelson-Williams C, Ellison, DH, Flavell, R, Booth, CJ, Lu Y, Geller, DS, Lifton, RP. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nature Genetics, in press

Earlier Research Results on this discovey

Proc Natl Acad Sci U S A. 2003 Jan 21;100(2):680-4. Epub 2003 Jan 6.

Molecular pathogenesis of inherited hypertension with hyperkalemia: the Na-Cl cotransporter is inhibited by wild-type but not mutant WNK4.

Wilson FH¹, Kahle KT, Sabath E, Lalioti MD, Rapson AK, Hoover RS, Hebert SC, Gamba G, Lifton RP.

Author information

Abstract

Mutations in the serine-threonine kinases WNK1 and WNK4 [with no lysine (K) at a key catalytic residue] cause pseudohypoaldosteronism type II (PHAII), a Mendelian disease featuring hypertension, hyperkalemia, hyperchloremia, and metabolic acidosis. Both kinases are expressed in the distal nephron, although the regulators and targets of WNK signaling cascades are unknown. The Cl(-) dependence of PHAII phenotypes, their sensitivity to thiazide diuretics, and the observation that they constitute a “mirror image” of the phenotypes resulting from loss of function mutations in the thiazide-sensitive Na-Cl cotransporter (NCCT) suggest that PHAII may result from increased NCCT activity due to altered WNK signaling. To address this possibility, we measured NCCT-mediated Na(+) influx and membrane expression in the presence of wild-type and mutant WNK4 by heterologous expression in Xenopus oocytes. Wild-type WNK4 inhibits NCCT-mediated Na-influx by reducing membrane expression of the cotransporter ((22)Na-influx reduced 50%, P < 1 x 10(-9), surface expression reduced 75%, P < 1 x 10(-14) in the presence of WNK4). This inhibition depends on WNK4 kinase activity, because missense mutations that abrogate kinase function prevent this effect. PHAII-causing missense mutations, which are remote from the kinase domain, also prevent inhibition of NCCT activity, providing insight into the pathophysiology of the disorder. The specificity of this effect is indicated by the finding that WNK4 and the carboxyl terminus of NCCT coimmunoprecipitate when expressed in HEK 293T cells. Together, these findings demonstrate that WNK4 negatively regulates surface expression of NCCT and implicate loss of this regulation in the molecular pathogenesis of an inherited form of hypertension.

Free PMC Article

Images from this publication.See all images (4)Free text

SOURCE

http://www.ncbi.nlm.nih.gov/pubmed/12515852

LISTEN TO AUDIO TAPE by Prof. Richard Lifton

http://streaming.yale.edu/opa/podcasts/audio/schools/health_and_medicine/lifton_092007.mp3

January 27, 2014

Richard Lifton

Yale’s Richard Lifton is one of eight world-changing researchers whose work is celebrated during a program airing tonight (Jan. 27) on the Science Channel at 9 p.m. EST.

Lifton, Sterling Professor of Genetics and chair of the Department of Genetics, received a $3 million Breakthrough Prize in Life Sciences, created by top Silicon Valley entrepreneurs.

The Science Channel program features the Dec. 12 ceremony where Lifton and others received their prize. The festivities were hosted by actor Kevin Spacey and featured such celebrities as Conan O’Brien, Glenn Close, Rob Lowe, and Michael C. Hall, as well as tech leaders Mark Zuckerberg, Larry Page, Sergey Brin, Anne Wojcicki, Jimmy Wales, and Yuri Milner.

SOURCE

http://news.yale.edu/2014/01/27/tonight-lifton-honored-star-studded-ceremony

Yale consortium awarded $6 million to study therapies for vascular disease

Tuesday, January 21, 2014

Contact

Helen Dodson / 203-436-3984

Stacey Buba / 203-432-1333

Read this article on YaleNews

An international research team spearheaded by William C. Sessa, the Alfred Gilman Professor of Pharmacology and professor of medicine (cardiology), has been awarded a $6 million Transatlantic Networks of Excellence grant from the Fondation Leducq in France.

Sessa will be the U.S. coordinator for the consortium as it explores the mechanisms of secreted microRNAs and microRNA-based therapies for vascular disease. Sessa will be joined by a European coordinator, Dr. Thomas Thum, director of the Institute for Molecular and Translational Therapeutic Strategies at Hanover Medical School in Germany, and five investigators including recent Yale recruit, Carlos Fenandez-Hernando, associate professor of comparative medicine. The grant will be distributed over five years.

Sessa is director of the vascular biology and therapeutics program and vice chairman of pharmacology at Yale School of Medicine.

Sessa has long worked at the intersection of pharmacology and cardiovascular disease. He is on the scientific advisory board of the William Harvey Research Institute and NIHR Biomedical Research Unit in London, and also served on the joint strategy committee for the Yale-UCL collaborative in cardiovascular research.

“I am grateful to Fondation Leducq for funding this new international collaboration to find new and effective ways to treat a disease that kills millions of people each year,” Sessa said. “We have assembled a fantastic team of world class scientists to tackle the basic questions of how microRNAs are packaged and transferred between cells, and their therapeutic potential in vascular diseases.”

Fondation Leducq is a French non-profit health research foundation. Its mission is to improve human health through international efforts to combat cardiovascular disease. To this end, Fondation Leducq created the Transatlantic Networks of Excellence in Cardiovascular Research Program, which is designed to promote collaborative research involving centers in North America and Europe in the areas of cardiovascular and neurovascular disease.

Yale has had two previous Leducq grants — to Dr. Richard Lifton, chair of genetics, and Dr. Michael Simons, director of the Yale Cardiovascular Research Center.

SOURCE

http://bbs.yale.edu/about/article.aspx?id=6569

International Activity

YALE-UCL Collaborative
London, United Kingdom (2011)
Dr. Lifton is on the Joint Strategy Committee for the Yale-UCL Collaborative, an alliance which will provide opportunities for high-level scientific research, clinical and educational collaboration across the institutions involved: Yale University, Yale School of Medicine, Yale-New Haven Hospital and UCL (University College London) and UCL Partners
Transatlantic Network on Hypertension-Renal Salt Handling in the Control of Blood Pressure
France (2007)
Drs Hebert and Lifton will join leading researchers in Switzerland, France and Mexico in a transatlantic collaboration aimed at pinpointing the kidney’s role in high blood pressure.

Education & Training

M.D.: Stanford University (1982)
Ph.D.: Stanford University (1986)

Honors & Recognition

National Academy of Sciences
The Basic Science Prize
American Heart Association
Homer Smith Award
American Society of Nephrology
MSD International Award
International Society of Hypertension

Research Interests

Molecular genetics of common human diseases

Research Summary

The common human diseases that account for the vast majority of morbidity and mortality in human populations are known to have underlying inherited components. Advances in human genetics have made the identification of genetic variants contributing to these traits feasible. Such identification promises to revolutionize the diagnostic and therapeutic approaches to these disorders. We have focused on cardiovascular and renal disease. To date, we have identified mutations underlying more than 20 human diseases; these include a host of diseases that define molecular determinants of hypertension, stroke and heart attack. We have gone on from these starting points to use biochemistry and animal models to define the physiologic mechanisms linking genotype and phenotype. These findings have provided new insight into normal and disease biology, are identifying new pathways underlying disease pathogenesis, and are identifying new targets for development of novel therapeutics.

Extensive Research Description

Cardiovascular disease is the leading cause of death world-wide. Epidemiologic studies have identified hypertension, high cholesterol, diabetes and smoking as major risk factors. By investigation of rare families recruited from around the world that segregate single genes with large effect, we have identified genes that contribute to these traits, putting a molecular face on their pathogenesis. For example, we have identified mutations in 8 genes that cause high blood pressure (hypertension) and another 8 that cause low blood pressure. These mutations all converge on a final common pathway, the regulation of net salt reabsorption in the kidney. These findings have established the key role of variation in renal salt handling in blood pressure variation, and have led to changes in the approach to treatment of this disease in the general population. They have also identified new therapeutic targets that are predicted to have greater efficacy with reduced side effects. Finally, they have identified new signaling pathways involved in the regulation of blood pressure homeostasis. We have taken similar approaches to another common disease, osteoporosis, with the identification of gain of function mutations in LRP5, a component of the Wnt signaling pathway, in development of high bone density. This finding has led to intensive efforts to identify small molecules that impact this pathway to protect against and/or reverse osteoporosis in the general population. Ongoing studies use both emerging and novel approaches to identification of genes that contribute to disease burden in the population, and to understanding the pathways that link genes to disease. Mutations that affect blood pressure in humans. A diagram of a nephron, the filtering unit of the kidney, is shown. The molecular pathways mediating NaCl reabsorption in individual renal cells along the nephron are shown, along with the pathway of the renin-angiotensin system, a major regulator of renal salt reabsorption. Inherited diseases affecting these pathways are indicated, with hypertensive disorders in red and hypotensive disorders in blue. From Lifton, Gharavi, and Geller. Cell, 104:545-556, 2001.

Selected Publications

Mani, A., et al. (2007). LRP6 mutation in a family with early coronary disease and metabolic risk factors. Science 315:1278-82.
Ring, A.M., et al. (2007). An SGK1 site in WNK4 regulates Na+ channel and K+ channel activity and has implications for aldosterone signaling and K+ homeostasis. Proc. Natl. Acad. Sci. (USA) 104:4025-9.
Lalioti MD, Zhang J, Volkman HM, Kahle KT, Hoffmann, KE, Toka HR, Nelson-Williams C, Ellison, DH, Flavell, R, Booth, CJ, Lu Y, Geller, DS, Lifton, RP. Wnk4 controls blood pressure and potassium homeostasis via regulation of mass and activity of the distal convoluted tubule. Nature Genetics, in press.
Wilson FH, Hariri A, Farhi A, Zhao H, Peterson K, Toka HR, Nelson- Williams C, Raja KM, Kashgarian M, Shulman GI, Scheinman SJ, Lifton RP. A cluster of metabolic defects caused by mutation in a mitochondrial tRNA. Science, 306:1190-94, 2004.
Boyden LM, Mao J, Belsky J, Mitzner L, Farhi A, Mitnick MA, Wu D, Insogna K, Lifton RP. High bone density due to a mutation in LDL-receptor-related protein 5. New Engl J Med. 346:1513-1521, 2002.
Wilson FH, Disse-Nicodème S, Choate KA, Ishikawa K, Nelson-Williams C, Desitter I, Gunel M, Milford DV, Lipkin GW, Achard JM, Feely MP, Dussol B, Berland Y, Unwin RJ, Mayan H, Simon DB, Farfel Z, Jeunemaitre X, Lifton RP. Human Hypertension Caused by Mutations in WNK Kinases. Science, 293:1107-1112, 2001.
Lifton RP, Gharavi A, Geller DS. Molecular mechanisms of human hypertension. Cell, 104:545-556, 2001.
Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G, Tsai TF, Sigler P, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science, 289:119-123, 2000.
Simon DB, Lu Y, Choate KA, Velazquez H, Al-Sabban E, Praga M, Casari G, Bettinelli A, Colussi G, Rodriguez-Soriano J, McCredie D, Milford D, Sanjad S, Lifton RP. Paracellin-1, a renal tight junction protein required for paracellular Mg2+ reabsorption. Science, 285:103-106, 1999.

SOURCE
http://bbs.yale.edu/people/richard_lifton-3.profile

PubMed Results: 10

Select item 225138461.

Protein phosphatase 1 modulates the inhibitory effect of With-no-Lysine kinase 4 on ROMK channels.

Lin DH, Yue P, Rinehart J, Sun P, Wang Z, Lifton R, Wang WH.

Am J Physiol Renal Physiol. 2012 Jul 1;303(1):F110-9. doi: 10.1152/ajprenal.00676.2011. Epub 2012 Apr 18.

PMID:

22513846

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 165287062.

Haplotype analysis in the presence of informatively missing genotype data.

Liu N, Beerman I, Lifton R, Zhao H.

Genet Epidemiol. 2006 May;30(4):290-300.

PMID:

16528706

[PubMed – indexed for MEDLINE]

Related citations

Select item 165282533.

Familial aggregation of primary glomerulonephritis in an Italian population isolate: Valtrompia study.

Izzi C, Sanna-Cherchi S, Prati E, Belleri R, Remedio A, Tardanico R, Foramitti M, Guerini S, Viola BF, Movilli E, Beerman I, Lifton R, Leone L, Gharavi A, Scolari F.

Kidney Int. 2006 Mar;69(6):1033-40.

PMID:

16528253

[PubMed – indexed for MEDLINE]

Related citations

Select item 127823554.

Mice lacking the B1 subunit of H+ -ATPase have normal hearing.

Dou H, Finberg K, Cardell EL, Lifton R, Choo D.

Hear Res. 2003 Jun;180(1-2):76-84.

PMID:

12782355

[PubMed – indexed for MEDLINE]

Related citations

Select item 113430495.

Glucocorticoid-remediable aldosteronism is associated with severe hypertension in early childhood.

Dluhy RG, Anderson B, Harlin B, Ingelfinger J, Lifton R.

J Pediatr. 2001 May;138(5):715-20.

PMID:

11343049

[PubMed – indexed for MEDLINE]

Related citations

Select item 102327426.

Elevated ambulatory blood pressure in 20 subjects with Williams syndrome.

Broder K, Reinhardt E, Ahern J, Lifton R, Tamborlane W, Pober B.

Am J Med Genet. 1999 Apr 23;83(5):356-60.

PMID:

10232742

[PubMed – indexed for MEDLINE]

Related citations

Select item 97986657.

Coincident acute myelogenous leukemia and ischemic heart disease: use of the cardioprotectant dexrazoxane during induction chemotherapy.

Woodlock TJ, Lifton R, DiSalle M.

Am J Hematol. 1998 Nov;59(3):246-8.

PMID:

9798665

[PubMed – indexed for MEDLINE]

Related citations

Select item 95012578.

In vivo phosphorylation of the epithelial sodium channel.

Shimkets RA, Lifton R, Canessa CM.

Proc Natl Acad Sci U S A. 1998 Mar 17;95(6):3301-5.

PMID:

9501257

[PubMed – indexed for MEDLINE]

Free PMC Article

Related citations

Select item 91562619.

Autotransplantation for relapsed or refractory non-Hodgkin’s lymphoma (NHL): long-term follow-up and analysis of prognostic factors.

Rapoport AP, Lifton R, Constine LS, Duerst RE, Abboud CN, Liesveld JL, Packman CH, Eberly S, Raubertas RF, Martin BA, Flesher WR, Kouides PA, DiPersio JF, Rowe JM.

Bone Marrow Transplant. 1997 May;19(9):883-90.

PMID:

9156261

[PubMed – indexed for MEDLINE]

Free Article

Related citations

Select item 881130410.

Clinical use of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in neutropenia associated with malignancy.

Lifton R, Bennett JM.

Hematol Oncol Clin North Am. 1996 Aug;10(4):825-39. Review.

PMID:

8811304

[PubMed – indexed for MEDLINE]

Related citations

SOURCE

http://www.ncbi.nlm.nih.gov/pubmed?cmd=Search&itool=pubmed_AbstractPlus&term=%22Lifton+R%22%5BAuthor%5D

Read Full Post »

Three-parent Baby-making: Practice of Modifying Oocytes for use in In-vitro Fertilization: FDA Hearing

Posted in Genomic Testing: Methodology for Diagnosis, Interviews with Scientific Leaders, Medical and Population Genetics, Personalized and Precision Medicine & Genomic Research, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, Reproductive Biology & Bio Instrumentation on February 26, 2014| Leave a Comment »

Three-parent Baby-making: Practice of Modifying Oocytes for use in In-vitro Fertilization: FDA Hearing

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #116: Three-parent Baby-making: Practice of Modifying Oocytes for use in In-vitro Fertilization: FDA Hearing. Published on 2/26/2014

WordCloud Image Produced by Adam Tubman

The US Food and Drug Administration wants to find out if the practice of modifying oocytes for use in in vitro fertilization is safe and scientifically sound, and held a hearing this week to launch a review of the process. Although it is sometimes referred to as three-parent baby-making, the procedure is not as kinky as it sounds, nor is it a likely set-up for a situation comedy, as very little DNA is contributed by the donor, but it has triggered some scientific, safety, and ethical concerns.

Specifically, the FDA’s Cellular, Tissue, and Gene Therapies Advisory Committee held a two-day meeting to hear about the use of cytoplasmic transfer, which enables women with inherited forms of mitochondrial disease to have healthy children by combining a healthy donor egg with nuclear genetic material from the mother before the IVF procedure.

The UK is already moving forward with permitting three-person IVF, but the procedure is not allowed in the US.

FDA is leaving the ethical questions and controversies about oocyte modification aside for now and seeking input on future clinical trials and the scientific, technological, and clinical issues involved and how they may affect the health of the mother and child.

In the New York Times, Sabrina Tavernise notes that although the treatments in question here are not what is generally thought of as genetic engineering, research into this area in general spurs fears in the US about how far science will go in human engineering.

“Every time we get a little closer to genetic tinkering to promote health — that’s exciting and scary,” Alan Copperman, director of the division of reproductive endocrinology and infertility at Mount Sinai Medical Center in New York, tells theTimes. “People are afraid it will turn into a dystopian brave new world.”

At the FDA meeting this week, Oregon Health Sciences University researcher Shoukrat Mitalipov, who has performed the procedure in monkeys in the US and contends that it is ready to be used in humans, took questions from the panel about the procedures he has used and the specifics of his experiments.

FDA for now plans to consider the science as it is, how it may be used, and whether it may be ready for expanded studies in humans.

“We haven’t made any decision about whether clinical trials will be allowed to proceed,” FDA’s Celia Witten tells the Times.

Marcy Darnovsky of the Center for Genetics and Society in a Times op-ed this weeksays these technologies are not ready, and crystallizes the angst many feel about human genetic tinkering.

She says, though, that they may have value, and that avoiding mitochondrial disease or helping women conceive are worthy goals.

“But these procedures are deeply problematic in terms of their medical risks and societal implications. Will the child be born healthy, or will the cellular disruptions created by this eggs-as-Lego pieces approach lead to problems later on? What about subsequent generations? And how far will we go in our efforts to engineer humans?” Darnovsky adds.

SOURCE

http://www.genomeweb.com//node/1354816?utm_source=SilverpopMailing&utm_medium=email&utm_campaign=Daily%20Scan%20Blog:%20FDA%20Examines%20’Three-Parent’%20IVF,%20This%20Week%20in%20Genome%20Biology,%20Cancer%20Risk%20Reduction,%20more%20-%2002/26/2014%2001:20:00%20PM

Read Full Post »

“Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Posted in Acute Myocardial Infarction, Atherogenic Processes & Pathology, Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Biomedical Measurement Science, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiomyopathy, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Chemical Biology and its relations to Metabolic Disease, Chemical Genetics, Computational Biology/Systems and Bioinformatics, Congenital Heart Disease, FDA Regulatory Affairs, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Healthcare costs and reimbursement, Human Immune System in Health and in Disease, Imaging-based Cancer Patient Management, Immunodiagnostics, Innovation in Immunology Diagnostics, Interviews with Scientific Leaders, Medical and Population Genetics, Metabolomics, Molecular Genetics & Pharmaceutical, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Nanotechnology for Drug Delivery, Nutrigenomics, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Pharmacologic toxicities, Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, Proteomics, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, Scientist: Career considerations, Technology Capital Expenses, Translational Research, Translational Science on February 10, 2014| Leave a Comment »

“Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US

Curator: Aviva Lev-Ari, PhD, RN

Article ID #111: “Sudden Cardiac Death,” SudD is in Ferrer inCode’s Suite of Cardiovascular Genetic Tests to be Commercialized in the US. Published on 2/10/2014

WordCloud Image Produced by Adam Tubman

Uncertainty around reimbursement for targeted NGS tests is faced by Molecular Diagnostic and Genomics Services companies

VIEW VIDEO

Democratization of Genomic Medicine: Michael Bolick @ TEDxTalks

Ferrer inCode’s Suite of Cardiovascular Genetic Tests included the following tests:

SudD inCode (Sudden Cardiac Death)
Cardio inCode,
Thrombo inCode, and
Nutri inCode

Selah Genomics, Ferrer inCode to Offer NGS-based Cardiovascular Test in US

2014/02/06

Selah Genomics, a Greenville, S.C.-based molecular diagnostic and genomics services company, has partnered with Spanish pharmaceutical company Ferrer inCode to commercialize Ferrer inCode’s suite of cardiovascular genetic tests in the US.

Selah will first validate Ferrer’s next-generation sequencing-based test for sudden cardiac death, SudD inCode, on Illumina’s MiSeq system to run out of its CLIA-certified laboratory.

Meantime, Selah plans to validate three other Ferrer inCode PCR-based cardiovascular tests — Cardio inCode, Thrombo inCode, and Nutri inCode — in its own lab using PCR, but may eventually combine the tests into one comprehensive panel to run on an NGS system, Selah CEO Michael Bolick told Clinical Sequencing News.

Selah already offers its PrecisionPath targeted Cancer Test in collaboration with the Greenville Health System’s Institute for Translational Oncology Research. All consenting cancer patients at ITOR receive the PrecisionPath test, which runs on Life Technologies’ Ion Torrent PGM and uses the Ion AmpliSeq technology.

Currently, Selah receives between 10 and 20 samples per week for PrecisionPath, and it plans to roll the test out nationwide later this year.

Bolick said that the company is also developing Hepatitis C and HIV assays for the MiSeq, and that the firm will likely purchase Illumina’s MiSeqDx, which recently received clearance from the US Food and Drug Administration.

Selah also collaborates with pharmaceutical companies to develop companion diagnostic tests. Bolick anticipates that the firm will use the MiSeqDx for those tests since they will “ultimately need [pre-market approval].” Having an FDA-cleared platform on which to develop the tests will be helpful in gaining a PMA designation, he said.

Selah also offers Exome Sequencing Services on the Ion Proton for research use only. In addition, it has a

Pacific Biosciences RS II and
Roche’s 454 GS FLX in house.

Bolick said that the company is currently using the PacBio machine for discovery work in infectious disease.

Ferrer inCode’s SudD inCode Test

currently assesses 55 genes related to structural heart problems that cause sudden cardiac arrest, Robert Jenkins, who manages Ferrer inCode’s UK and Americas groups, told CSN. However, the company is planning to

expand the test to 104 genes and also to include
genes related to conductive myopathy,
sudden infant death, and
aneurysms.

While the test sequences the entire genes, only well-known causative variants are reported, Jenkins said. However, the firm has been collecting all the sequenced variants, so it could potentially add content to the test if enough evidence is gathered to validate any of those variants as clinically significant.

Ferrer inCode currently runs SudD inCode on the MiSeq as an LDT, which is how Selah will validate and market the test in the US.

Jenkins said that for now, Ferrer plans to keep the Cardio, Nutri, and Thrombo inCode tests PCR-based.

Cardio inCode looks at around 125 variants involved in genetic risk for cardiac disease.

When it is used with traditional markers such as

lipid profiling, an individual’s
smoking and drinking habits, and
body mass index,

Jenkins said the genetic test helps to reclassify around 20 percent to 25 percent of individuals deemed in the intermediate risk category as either high or low risk.

Thrombo inCode Test

is an approximately 20-variant thrombosis test for individuals that have had a thrombotic event or who have had a history of unsuccessful pregnancies. Often, the cause of thrombosis can go unexplained via testing from serological workups, Jenkins said.

Nutri inCode Test

is a nutrigenomics test that looks at around 90 SNPs. In combination with lifestyle factors, it helps individuals develop a tailored genetics-based plan to reduce obesity, Jenkins said.

Bolick said that while Selah will validate and develop each of these tests individually out of its laboratory, it is also deciding whether to combine the tests into one next-gen sequencing-based test.

Jeremy Stuart, Selah’s VP of genomic services, told CSN that one option would be to incorporate the individual SNPs assessed in the Thrombo, Cardio, and Nutri tests into the SudD test.

Bolick said that the company is now in discussions with third party payors about reimbursement for the tests and is readying a regional pilot program to offer the sequencing-based cardiovascular test as part of a corporate wellness program. The pilot will help Selah figure out a pricing structure and will also demonstrate a “return on investment to the corporation, by allowing for better determination of risk of heart disease,” Bolick said.

Currently, Selah’s other NGS test, PrecisionPath, is being paid for by ITOR. However, Bolick said that initial conversations with third party payors about launching the assay outside of the Greenville Health System have been positive.

Reimbursement success will play a role in determining how the company expands beyond its current tests. For instance, while Selah is interested in moving into

clinical exome sequencing,

Stuart said that right now there is a “lot of uncertainty around reimbursement for targeted NGS tests, let alone exome sequencing.” Selah will first “establish reimbursement for those and then may expand into what’s possible for exome sequencing,” Stuart said. But currently, the exome market is research use only.

SOURCE

http://www.ferrerincode.com/en/node/98

Selah Genomics

SELAH GENOMICS: HARNESS THE POWER OF PRECISION FOR MORE PERSONALIZED TREATMENT

Selah Genomics is a clinical diagnostic specialist supporting healthcare providers and the pharmaceutical industry with advanced molecular and genomic diagnostic services. Selah’s services add value to early stage drug development, clinical trials and regulatory processes in the pharmaceutical industry and helps clinicians and healthcare providers treat and monitor patients, thereby improving patient outcomes.

With the Power of Precision, Selah Genomics provides the best in molecular diagnostic testing, assay validation and genomic profiling that all leads to one common goal: to provide better outcomes for patients.

Michael Bolick, CEO

Michael is a serial entrepreneur with 25 years of experience in the life science and healthcare industries. Most recently, he led a management buyout of Lab21 Ltd’s US-based operations to form Selah Genomics Inc. Prior to co-founding Selah Genomics, Michael served as President of Lab21 Inc which was formed following Lab21 Ltd’s acquisition of his prior company, Selah Technologies LLC. He founded Selah Technologies LLC to commercialize nanotechnologies licensed from Clemson University. Selah focused these nanotechnologies to enable doctors to see cancer during surgery. Prior to founding Selah Technologies, Michael’s career included roles of increasing responsibility in the pharmaceutical sector.

Michael is a Fellow in the Liberty Fellowship Class of 2011. Liberty Fellowship is a program designed specifically for emerging state leaders to reinforce values necessary to lead an exemplary life both personally and professionally. Michael serves as Immediate Past Chair of SCBIO, South Carolina’s Life Sciences Industry Association. Michael earned his bachelor’s degree in Chemical Engineering from North Carolina State University.

Selah Genomics specializes in supporting healthcare providers and the pharmaceutical industry with advanced molecular and genomic diagnostic services.

read more »

Latest News

Find out what the buzz is about
- Greenville Health System, Roswell Park Adopt Targeted Sequencing in Cancer Treatment
  
  8 May 2013
- Selah, GHS expand personalized medicine
  
  2 May 2013
- The Democratization of Genomic Medicine: Michael Bolick at TEDxGreenville
  
  21 Apr 2013
- Greenville Magazine features Selah Genomics
  
  1 Apr 2013
- Upstate Biotech Firm Expands to Columbia
  
  14 Mar 2013
- Genetic Engineering and Biotechnology News; “Selah Genomics Establishes Second Clinical Genomics Center”
  
  20 Feb 2013
- Selah Genomics Forms Second Clinical Genomic Center
  
  19 Feb 2013
Clinical Laboratory

Helping physicians by applying our scientific expertise and skills in advanced molecular diagnostic assay development in a CLIA-certified laboratory.

read more »
PrecisionPath™

Genomic profiling of solid tumors, identifying actionable targets today and enabling the discovery of clinically relevant genes for tomorrow.

read more »
Genomic Services

Selah Genomics provides a suite of services focused on support of molecular biomarker discovery, assay validation and prospective/retrospective clinical trial testing in support of companion diagnostic development and commercialization.

read more »

SOURCE

http://selahgenomics.com/

THE FAST-TRACK TO DISCOVERY AND CLINICAL UTILIZATION

Selah Genomics provides a suite of services focused on support of molecular biomarker discovery, assay validation and prospective/retrospective clinical trial testing in support of companion diagnostic development and commercialization. Selah operates NGS platforms from Life Technologies, Illumina, Roche and PacBio as well as an array of real time PCR and other supporting instrumentation systems. We help you select the best platform for each Project in support of your particular goals. Our prime focus – to help fast-track the clinical utilization and commercialization of your biomarker.

Selah enjoys a key corporate relationship with the Greenville Health System’s (GHS) Institute of Translational Oncology Research (ITOR) conducting multiple clinical trials and identification of new oncology biomarkers.

GHS is the 13th largest public hospital in the United States and ITOR has the largest Phase 1 clinical trial program in South Carolina, including a track record of 16 first-in-human trials. The close relationship with ITOR is an enormous asset for Selah. Not only does it allow Selah to provide state-of-the-art molecular diagnostics support for ITOR clinical studies but it leads to first-hand daily interaction with cancer physicians. This interaction stimulates early identification and development of new biomarker panels.

Selah’s Clinical Genomics Center at ITOR is physically located within GHS & ITOR. In addition, Selah operates a Clinical Genomics Center at Innovista on the campus of the University of South Carolina.

SOURCE

http://selahgenomics.com/genomic-services/

Read Full Post »

« Newer Posts - Older Posts »

Archive for the ‘Medical and Population Genetics’ Category

Summary – Volume 4, Part 2: Translational Medicine in Cardiovascular Diseases

1. The establishment of national and international outcomes databases for procedures by specialist medical societies

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents Curator: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

and more

2. The identification of problem areas, particularly in activation of the prothrombotic pathways, infection control to an extent, and targeting of pathways leading to progression or to arrythmogenic complications.

Anticoagulation genotype guided dosing Larry H. Bernstein, MD, FCAP, Author and Curator http://pharmaceuticalintelligence.com/2013/12/08/anticoagulation-genotype-guided-dosing/

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents Curator: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

The Effects of Aprotinin on Endothelial Cell Coagulant Biology Co-Author (Kamran Baig, MBBS, James Jaggers, MD, Jeffrey H. Lawson, MD, PhD) and Curator http://pharmaceuticalintelligence.com/2013/07/20/the-effects-of-aprotinin-on-endothelial-cell-coagulant-biology/

Pharmacogenomics – A New Method for Druggability Author and Curator: Demet Sag, PhD http://pharmaceuticalintelligence.com/2014/04/28/pharmacogenomics-a-new-method-for-druggability/

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage Author: Larry H Bernstein, MD, FCAP http://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-Sepsis-and-the-Cardiovascular-System-at-its-End-Stage/

3. Development of procedures that use a safer materials in vascular management.

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents Curator: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

Vascular Repair: Stents and Biologically Active Implants Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, RN, PhD http://pharmaceuticalintelligence.com/2013/05/04/stents-biologically-active-implants-and-vascular-repair/

Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN http://PharmaceuticalIntelligence.com/2013/04/25/Contributions-to-vascular-biology/

MedTech & Medical Devices for Cardiovascular Repair – Curations by Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2014/04/17/medtech-medical-devices-for-cardiovascular-repair-curation-by-aviva-lev-ari-phd-rn/

4. Discrimination of cases presenting for treatment based on qualifications for medical versus surgical intervention.

ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery Reporter: Aviva Lev-Ari, PhD, RN http://pharmaceuticalintelligence.com/2013/11/05/accaha-guidelines-for-coronary-artery-bypass-graft-surgery/

5. This has become possible because of the advances in our knowledge of key related pathogenetic mechanisms involving gene expression and cellular regulation of complex mechanisms.

What is the key method to harness Inflammation to close the doors for many complex diseases? Author and Curator: Larry H Bernstein, MD, FCAP http://pharmaceuticalintelligence.com/2014/03/21/what-is-the-key-method-to-harness-inflammation-to-close-the-doors-for-many-complex-diseases/

Notable Contributions to Regenerative Cardiology Author and Curator: Larry H Bernstein, MD, FCAP and Article Commissioner: Aviva Lev-Ari, PhD, RD http://pharmaceuticalintelligence.com/2013/10/20/notable-contributions-to-regenerative-cardiology/

I shall identify continuing developments in cardiovascular diagnostics, therapeutics, and bioengineering that is and has been emerging.

Efficacy and Safety of Dabigatran Compared With Warfarin in Relation to Baseline Renal Function in Patients With Atrial Fibrillation: A RE-LY (Randomized Evaluation of Long-term Anticoagulation Therapy) Trial Analysis

Carísi A Polanczyk, Samir Schneid, Betina V Imhof, Mariana Furtado, Carolina Pithan, Luis E Rohde, Jorge P Ribeiro

Acellular Biomaterials: An Evolving Alternative to Cell-Based Therapies

Share this:

Like this:

Summary of Translational Medicine – e-Series A: Cardiovascular Diseases, Volume Four – Part 1

There are some developments that deserve additional development:

Electron Transport and Bioenergetics

Synthetic Biology

Introduction to Synthetic Biology and Metabolic Engineering

David Bartel: micro-RNAs

Calcium Cycling in Synthetic and Contractile Phasic or Tonic Vascular Smooth Muscle Cells

Time for New DNA Synthesis and Sequencing Cost Curves

Startup to Strengthen Synthetic Biology and Regenerative Medicine Industries with Cutting Edge Cell Products

Life at the Speed of Light

Where Will the Century of Biology Lead Us?

Biology + Engineering = Synthetic Biology

Genomics Now—and Beyond the Bubble

Stepping into DIYbio and Synthetic Biology at ScienceHack

Share this:

Like this:

Pharmacogenomics – A New Method for Druggability

Further reading :

Other articles on Pharmacogenomics published in this Open Access Online Scientific Journal include the following:

Pharmacogenomics for Cardiovascular Diseases

Share this:

Like this:

Acetylation and Deacetylation of non-Histone Proteins

Acetylation and Deacetylation of non-histone proteins

Abbreviations:

Protein Acetylation: Much More than Histone Acetylation

Share this:

Like this:

PostTranslational Modification of Proteins

Posttranslational modification of proteins: expanding nature’s inventory.

Share this:

Like this:

Cancer Research: Curations and Reporting: Aviva Lev-Ari, PhD, RN

General

Reporting

Novel Therapies for Cancer

Genomics and Cancer

Cancer Research by Cancer Type

Breast

Breast/Ovarian

Breast/Personalized Medicine

Colon

Epigenetics

Gastric

Gastric/Personalized Medicine

Skin Cancer

Prostate Cancer

Head & Neck

Cancer and the Human Heart – Correlation between Cancer and Cardiovascular Diseases

Share this:

Like this:

Methodology for Conference Coverage using Social Media:

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Anticoagulation genotype guided dosing
Larry H. Bernstein, MD, FCAP, Author and Curator
http://pharmaceuticalintelligence.com/2013/12/08/anticoagulation-genotype-guided-dosing/

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

The Effects of Aprotinin on Endothelial Cell Coagulant Biology
Co-Author (Kamran Baig, MBBS, James Jaggers, MD, Jeffrey H. Lawson, MD, PhD) and Curator
http://pharmaceuticalintelligence.com/2013/07/20/the-effects-of-aprotinin-on-endothelial-cell-coagulant-biology/

Pharmacogenomics – A New Method for Druggability Author and Curator: Demet Sag, PhD
http://pharmaceuticalintelligence.com/2014/04/28/pharmacogenomics-a-new-method-for-druggability/

Advanced Topics in Sepsis and the Cardiovascular System at its End Stage Author: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2013/08/18/advanced-topics-in-Sepsis-and-the-Cardiovascular-System-at-its-End-Stage/

Stent Design and Thrombosis: Bifurcation Intervention, Drug Eluting Stents (DES) and Biodegrable Stents
Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/08/06/stent-design-and-thrombosis-bifurcation-intervention-drug-eluting-stents-des-and-biodegrable-stents/

Biomaterials Technology: Models of Tissue Engineering for Reperfusion and Implantable Devices for Revascularization
Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/05/05/bioengineering-of-vascular-and-tissue-models/

Vascular Repair: Stents and Biologically Active Implants
Author and Curator: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, RN, PhD
http://pharmaceuticalintelligence.com/2013/05/04/stents-biologically-active-implants-and-vascular-repair/

Drug Eluting Stents: On MIT’s Edelman Lab’s Contributions to Vascular Biology and its Pioneering Research on DES
Author: Larry H Bernstein, MD, FACP and Curator: Aviva Lev-Ari, PhD, RN
http://PharmaceuticalIntelligence.com/2013/04/25/Contributions -to-vascular-biology/

MedTech & Medical Devices for Cardiovascular Repair – Curations by Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2014/04/17/medtech-medical-devices-for-cardiovascular-repair-curation-by-aviva-lev-ari-phd-rn/

ACC/AHA Guidelines for Coronary Artery Bypass Graft Surgery Reporter: Aviva Lev-Ari, PhD, RN
http://pharmaceuticalintelligence.com/2013/11/05/accaha-guidelines-for-coronary-artery-bypass-graft-surgery/

What is the key method to harness Inflammation to close the doors for many complex diseases?
Author and Curator: Larry H Bernstein, MD, FCAP
http://pharmaceuticalintelligence.com/2014/03/21/what-is-the-key-method-to-harness-inflammation-to-close-the-doors-for-many-complex-diseases/

Notable Contributions to Regenerative Cardiology Author and Curator: Larry H Bernstein, MD, FCAP and Article Commissioner: Aviva Lev-Ari, PhD, RD
http://pharmaceuticalintelligence.com/2013/10/20/notable-contributions-to-regenerative-cardiology/