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Archive for the ‘Chemical Biology and its relations to Metabolic Disease’ Category


Regulatory MicroRNAs in Aberrant Cholesterol Transport and Metabolism

Curator: Marzan Khan, B.Sc

Aberrant levels of lipids and cholesterol accumulation in the body lead to cardiometabolic disorders such as atherosclerosis, one of the leading causes of death in the Western World(1). The physical manifestation of this condition is the build-up of plaque along the arterial endothelium causing the arteries to constrict and resist a smooth blood flow(2). This obstructive deposition of plaque is merely the initiation of atherosclerosis and is enriched in LDL cholesterol (LDL-C) as well foam cells which are macrophages carrying an overload of toxic, oxidized LDL(2). As the condition progresses, the plaque further obstructs blood flow and creates blood clots, ultimately leading to myocardial infarction, stroke and other cardiovascular diseases(2). Therefore, LDL is referred to as “the bad cholesterol”(2).

Until now, statins are most widely prescribed as lipid-lowering drugs that inhibit the enzyme 3-hydroxy-3methylgutaryl-CoA reductase (HMGCR), the rate-limiting step in de-novo cholesterol biogenesis (1). But some people cannot continue with the medication due to it’s harmful side-effects(1). With the need to develop newer therapeutics to combat cardiovascular diseases, Harvard University researchers at Massachusetts General Hospital discovered 4 microRNAs that control cholesterol, triglyceride, and glucose homeostasis(3)

MicroRNAs are non-coding, regulatory elements approximately 22 nucleotides long, with the ability to control post-transcriptional expression of genes(3). The liver is the center for carbohydrate and lipid metabolism. Stringent regulation of endogenous LDL-receptor (LDL-R) pathway in the liver is crucial to maintain a minimal concentration of LDL particles in blood(3). A mechanism whereby peripheral tissues and macrophages can get rid of their excess LDL is mediated by ATP-binding cassette, subfamily A, member 1 (ABCA1)(3). ABCA1 consumes nascent HDL particles- dubbed as the “good cholesterol” which travel back to the liver for its contents of triglycerides and cholesterol to be excreted(3).

Genome-wide association studies (GWASs) meta-analysis carried out by the researchers disclosed 4 microRNAs –(miR-128-1, miR-148a, miR-130b, and miR-301b) to lie close to single-nucleotide polymorphisms (SNPs) associated with abnormal metabolism and transport of lipids and cholesterol(3) Experimental analyses carried out on relevant cell types such as the liver and macrophages have proven that these microRNAs bind to the 3’ UTRs of both LDL-R and ABCA1 transporters, and silence their activity. Overexpression of miR-128-1 and miR148a in mice models caused circulating HDL-C to drop. Corroborating the theory under investigation further, their inhibition led to an increased clearance of LDL from the blood and a greater accumulation in the liver(3).

That the antisense inhibition of miRNA-128-1 increased insulin signaling in mice, propels us to hypothesize that abnormal expression of miR-128-1 might cause insulin resistance in metabolic syndrome, and defective insulin signaling in hepatic steatosis and dyslipidemia(3)

Further examination of miR-148 established that Liver-X-Receptor (LXR) activation of the Sterol regulatory element-binding protein 1c (SREBP1c), the transcription factor responsible for controlling  fatty acid production and glucose metabolism, also mediates the expression of miR-148a(4,5) That the promoter region of miR-148 contained binding sites for SREBP1c was shown by chromatin immunoprecipitation combined with massively parallel sequencing (ChIP-seq)(4). More specifically, SREBP1c attaches to the E-box2, E-box3 and E-box4 elements on miR-148-1a promoter sites to control its expression(4).

Earlier, the same researchers- Andres Naars and his team had found another microRNA called miR-33 to block HDL generation, and this blockage to reverse upon antisense targeting of miR-33(6).

These experimental data substantiate the theory of miRNAs being important regulators of lipoprotein receptors and transporter proteins as well as underscore the importance of employing antisense technologies to reverse their gene-silencing effects on LDL-R and ABCA1(4). Such a therapeutic approach, that will consequently lower LDL-C and promote HDL-C seems to be a promising strategy to treat atherosclerosis and other cardiovascular diseases(4).

References:

1.Goedeke L1,Wagschal A2,Fernández-Hernando C3, Näär AM4. miRNA regulation of LDL-cholesterol metabolism. Biochim Biophys Acta. 2016 Dec;1861(12 Pt B):. Biochim Biophys Acta. 2016 Dec;1861(12 Pt B):2047-2052

https://www.ncbi.nlm.nih.gov/pubmed/26968099

2.MedicalNewsToday. Joseph Nordgvist. Atherosclerosis:Causes, Symptoms and Treatments. 13.08.2015

http://www.medicalnewstoday.com/articles/247837.php

3.Wagschal A1,2, Najafi-Shoushtari SH1,2, Wang L1,2, Goedeke L3, Sinha S4, deLemos AS5, Black JC1,6, Ramírez CM3, Li Y7, Tewhey R8,9, Hatoum I10, Shah N11, Lu Y11, Kristo F1, Psychogios N4, Vrbanac V12, Lu YC13, Hla T13, de Cabo R14, Tsang JS11, Schadt E15, Sabeti PC8,9, Kathiresan S4,6,8,16, Cohen DE7, Whetstine J1,6, Chung RT5,6, Fernández-Hernando C3, Kaplan LM6,10, Bernards A1,6,16, Gerszten RE4,6, Näär AM1,2. Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis. . Nat Med.2015 Nov;21(11):1290

https://www.ncbi.nlm.nih.gov/pubmed/26501192

4.Goedeke L1,2,3,4, Rotllan N1,2, Canfrán-Duque A1,2, Aranda JF1,2,3, Ramírez CM1,2, Araldi E1,2,3,4, Lin CS3,4, Anderson NN5,6, Wagschal A7,8, de Cabo R9, Horton JD5,6, Lasunción MA10,11, Näär AM7,8, Suárez Y1,2,3,4, Fernández-Hernando C1,2,3,4. MicroRNA-148a regulates LDL receptor and ABCA1 expression to control circulating lipoprotein levels. Nat Med. 2015 Nov;21(11):1280-9.

https://www.ncbi.nlm.nih.gov/pubmed/26437365

5.Eberlé D1, Hegarty B, Bossard P, Ferré P, Foufelle F. SREBP transcription factors: master regulators of lipid homeostasis. Biochimie. 2004 Nov;86(11):839-48.

https://www.ncbi.nlm.nih.gov/pubmed/15589694

6.Harvard Medical School. News. MicoRNAs and Metabolism.

https://hms.harvard.edu/news/micrornas-and-metabolism

7. MGH – Four microRNAs identified as playing key roles in cholesterol, lipid metabolism

http://www.massgeneral.org/about/pressrelease.aspx?id=1862

 

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

 

  • Cardiovascular Diseases, Volume Three: Etiologies of Cardiovascular Diseases: Epigenetics, Genetics and Genomics,

on Amazon since 11/29/2015

http://www.amazon.com/dp/B018PNHJ84

 

HDL oxidation in type 2 diabetic patients

Larry H. Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/2015/11/27/hdl-oxidation-in-type-2-diabetic-patients/

 

HDL-C: Target of Therapy – Steven E. Nissen, MD, MACC, Cleveland Clinic vs Peter Libby, MD, BWH

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2014/11/07/hdl-c-target-of-therapy-steven-e-nissen-md-macc-cleveland-clinic-vs-peter-libby-md-bwh/

 

High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk

Curator: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/03/31/high-density-lipoprotein-hdl-an-independent-predictor-of-endothelial-function-artherosclerosis-a-modulator-an-agonist-a-biomarker-for-cardiovascular-risk/

 

Risk of Major Cardiovascular Events by LDL-Cholesterol Level (mg/dL): Among those treated with high-dose statin therapy, more than 40% of patients failed to achieve an LDL-cholesterol target of less than 70 mg/dL.

Reporter: Aviva Lev-Ari, PhD., RN

https://pharmaceuticalintelligence.com/2014/07/29/risk-of-major-cardiovascular-events-by-ldl-cholesterol-level-mgdl-among-those-treated-with-high-dose-statin-therapy-more-than-40-of-patients-failed-to-achieve-an-ldl-cholesterol-target-of-less-th/

 

LDL, HDL, TG, ApoA1 and ApoB: Genetic Loci Associated With Plasma Concentration of these Biomarkers – A Genome-Wide Analysis With Replication

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/12/18/ldl-hdl-tg-apoa1-and-apob-genetic-loci-associated-with-plasma-concentration-of-these-biomarkers-a-genome-wide-analysis-with-replication/

 

Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2013/04/15/two-mutations-in-a-pcsk9-gene-eliminates-a-protein-involve-in-controlling-ldl-cholesterol/

Artherogenesis: Predictor of CVD – the Smaller and Denser LDL Particles

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2012/11/15/artherogenesis-predictor-of-cvd-the-smaller-and-denser-ldl-particles/

 

A Concise Review of Cardiovascular Biomarkers of Hypertension

Curator: Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/04/25/a-concise-review-of-cardiovascular-biomarkers-of-hypertension/

 

Triglycerides: Is it a Risk Factor or a Risk Marker for Atherosclerosis and Cardiovascular Disease ? The Impact of Genetic Mutations on (ANGPTL4) Gene, encoder of (angiopoietin-like 4) Protein, inhibitor of Lipoprotein Lipase

Reporters, Curators and Authors: Aviva Lev-Ari, PhD, RN and Larry H. Bernstein, MD, FCAP

https://pharmaceuticalintelligence.com/2016/03/13/triglycerides-is-it-a-risk-factor-or-a-risk-marker-for-atherosclerosis-and-cardiovascular-disease-the-impact-of-genetic-mutations-on-angptl4-gene-encoder-of-angiopoietin-like-4-protein-that-in/

 

Excess Eating, Overweight, and Diabetic

Larry H Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/2015/11/15/excess-eating-overweight-and-diabetic/

 

Obesity Issues

Larry H. Bernstein, MD, FCAP, Curator

https://pharmaceuticalintelligence.com/2015/11/12/obesity-issues/

 

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3D Liver Model in a Droplet

Curator: Marzan Khan, BSc

Recently, a Harvard University Professor of Physics and Applied Physics, David Weitz and his team of researchers have successfully generated 3D models of liver tissue composed of two different kinds of liver cells, precisely compartmentalized in a core-shell droplet, using the microfluidics approach(1). Compared to alternative in-vitro methods, this approach comes with more advantages – it is cost-effective, can be quickly assembled and produces millions of organ droplets in a second(1). It is the first “organ in a droplet” technology that enables two disparate liver cells to physically co-exist and exchange biochemical information, thus making it a good mimic of the organ in vivo(1).

Liver tissue models are used by researchers to investigate the effect of drugs and other chemical compounds, either alone or in combination on liver toxicity(2). The liver is the primary center of drug metabolism, detoxification and removal and all of these processes need to be carried out systematically in order to maintain a homeostatic environment within the body(2) Any deviation from the steady state will shift the dynamic equilibrium of metabolism, leading to production of reactive oxygen species (ROS)(2). These are harmful because they will exert oxidative stress on the liver, and ultimately cause the organ to malfunction. Drug-induced liver toxicity is a critical problem – 10% of all cases of acute hepatitis, 5% of all hospital admissions, and 50% of all acute liver failures are caused by it(2).

Before any novel drug is launched into the market, it is tested in-vitro, in animal models, and then progresses onto human clinical trials(1). Weitz’s system can produce up to one-thousand organ droplets per second, each of which can be used in an experiment to test for drug toxicity(1). Clarifying further, he asserts that “Each droplet is like a mini experiment. Normally, if we are running experiments, say in test tubes, we need a milliliter of fluid per test tube. If we were to do a million experiments, we would need a thousand liters of fluid. That’s the equivalent of a thousand milk jugs! Here, each droplet is only a nanoliter, so we can do the whole experiment with one milliliter of fluid, meaning we can do a million more experiments with the same amount of fluid.”

Testing hepatocytes alone on a petri dish is a poor indicator of liver-specific functions because the liver is made up of multiple cells systematically arranged on an extracellular matrix and functionally interdependent(3). The primary hepatocytes, hepatic stellate cells, Kupffer cells, endothelial cells and fibroblasts form the basic components of a functioning liver(3). Weitz’s upgraded system contains hepatocytes (that make up the majority of liver cells and carry out most of the important functions) supported by a network of fibroblasts(3). His microfluidic chip is comprised of a network of constricted, circular channels spanning the micrometer range, the inner phase of which contains hepatocytes mixed in a cell culture solution(3). The surrounding middle phase accommodates fibroblasts in an alginate solution and the two liquids remain separated due to differences in their chemical properties as well as the physics of fluids travelling in narrow channels. Addition of a fluorinated carbon oil interferes with the two aqueous layers, forcing them to become individual monodisperse droplets(3). The hydrogel shell is completed when a 0.15% solution of acetic acid facilitates the cross-linking of alginate to form a gelatinous shell, locking the fibroblasts in place(3). Thus, the aqueous core of hepatocytes are encapsulated by fibroblasts confined to a strong hydrogel network, creating a core-shell hydrogel scaffold of 3D liver micro-tissue in a droplet(3). Using empirical analysis, scientists have shown that albumin secretion and urea synthesis (two important markers of liver function) were significantly higher in a co-culture of hepatocytes and fibroblasts 3D core-shell spheroids compared to a monotypic cell-culture of hepatocyte-only spheroids(3). These results validate the theory that homotypic as well as heterotypic communication between cells are important to achieve optimal organ function in vitro(3).

This system of creating micro-tissues in a droplet with enhanced properties is a step-forward in biomedical science(3). It can be used in experiments to test for a myriad of drugs, chemicals and cosmetics on different human tissue samples, as well as to understand the biological connectivity of contrasting cells(3).

diagram

Image source: DOI: 10.1039/c6lc00231

A simple demonstration of the microfluidic chip that combines different solutions to create a core-shell droplet consisting of two different kinds of liver cells.

References:

  1. National Institute of Biomedical Imaging and Bioengineering. (2016, December 13). New device creates 3D livers in a droplet.ScienceDaily. Retrieved February 9, 2017 from https://www.sciencedaily.com/releases/2016/12/161213112337.htm
  2. Singh, D., Cho, W. C., & Upadhyay, G. (2015). Drug-Induced Liver Toxicity and Prevention by Herbal Antioxidants: An Overview.Frontiers in Physiology,6, 363. http://doi.org/10.3389/fphys.2015.00363
  3. Qiushui Chen, Stefanie Utech, Dong Chen, Radivoje Prodanovic, Jin-Ming Lin and David A. Weitz; Controlled assembly of heterotypic cells in a core– shell scaffold: organ in a droplet; Lab Chip, 2016, 16, 1346; DOI: 10.1039/c6lc00231

Other related articles on 3D on a Chip published in this Open Access Online Scientific Journal include the following:

 

What could replace animal testing – ‘Human-on-a-chip’ from Lawrence Livermore National Laboratory

Reporter: Aviva Lev-Ari, PhD, RN

AGENDA for Second Annual Organ-on-a-Chip World Congress & 3D-Culture Conference, July 7-8, 2016, Wyndham Boston Beacon Hill by SELECTBIO US

Reporter: Aviva Lev-Ari, PhD, RN

Medical MEMS, BioMEMS and Sensor Applications

Curator and Reporter: Aviva Lev-Ari, PhD, RN

Contribution to Inflammatory Bowel Disease (IBD) of bacterial overgrowth in gut on a chip

Larry H. Bernstein, MD, FCAP, Curator

Current Advances in Medical Technology

Larry H. Bernstein, MD, FCAP, Curator

 

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

 

Alnylam down as it halts development for RNAi liver disease candidate

by Stacy Lawrence

LIVE 9/21 8AM to 2:40PM Targeting Cardio-Metabolic Diseases: A focus on Liver Fibrosis and NASH Targets at CHI’s 14th Discovery On Target, 9/19 – 9/22/2016, Westin Boston Waterfront, Boston

Reporter: Aviva Lev-Ari, PhD, RN

2016 Nobel in Economics for Work on The Theory of Contracts to winners: Oliver Hart and Bengt Holmstrom

Reporter: Aviva Lev-Ari, PhD, RN

LIVE 9/20 2PM to 5:30PM New Viruses for Therapeutic Gene Delivery at CHI’s 14th Discovery On Target, 9/19 – 9/22/2016, Westin Boston Waterfront, Boston

Reporter: Aviva Lev-Ari, PhD, RN

Seven Cancers: oropharynx, larynx, oesophagus, liver, colon, rectum and breast are caused by Alcohol Consumption

Reporter: Aviva Lev-Ari, PhD, RN

 

Other related articles on 3D on a Chip published in this Open Access Online Scientific Journal include the following:

 

Liquid Biopsy Chip detects an array of metastatic cancer cell markers in blood – R&D @Worcester Polytechnic Institute,  Micro and Nanotechnology Lab

Reporters: Tilda Barliya, PhD and Aviva Lev-Ari, PhD, RN

Trovagene’s ctDNA Liquid Biopsy urine and blood tests to be used in Monitoring and Early Detection of Pancreatic Cancer

Reporters: David Orchard-Webb, PhD and Aviva Lev-Ari, PhD, RN

Liquid Biopsy Assay May Predict Drug Resistance

Curator: Larry H. Bernstein, MD, FCAP

One blood sample can be tested for a comprehensive array of cancer cell biomarkers: R&D at WPI

Curator: Marzan Khan, B.Sc

Real Time Coverage of the AGENDA for Powering Precision Health (PPH) with Science, 9/26/2016, Cambridge Marriott Hotel, Cambridge, MA

Reporter: Aviva Lev-Ari, PhD, RN

 

 

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Functional Analysis of the Microbiome for Development of Potential Therapeutic Approaches to Weight Regain

Reporter: Aviva Lev-Ari, PhD, RN

 

Transplanting fecal microbes to prevent recurring obesity

Finally, the researchers used these insights to develop new treatments for recurrent obesity. They implanted formerly obese mice with gut microbes from mice that had never been obese. This fecal microbiome transplantation erased the “memory” of obesity in these mice when they were re-exposed to a high-calorie diet, preventing excessive recurrent obesity.

Gut Microbes Contribute to Recurrent ‘Yo-Yo’ Obesity, Study Shows

By Einat Paz-Frankel, NoCamels December 18, 2016

Researchers at Israel’s Weizmann Institute of Science have shown in mice that intestinal microbes – collectively termed the gut microbiome – play an unexpectedly important role in exacerbated post-dieting weight gain, and that this common phenomenon may in the future be prevented or treated by altering the composition or function of the microbiome.

“We’ve shown in obese mice that following successful dieting and weight loss, the microbiome retains a ‘memory’ of previous obesity,” Elinav said in a statement. “This persistent microbiome accelerated the regaining of weight when the mice were put back on a high-calorie diet or ate regular food in excessive amounts.”

http://nocamels.com/2016/12/gut-microbes-recurrent-obesity-diet/

 

Original Research

Persistent microbiome alterations modulate the rate of post-dieting weight regain

Nature (2016) doi:10.1038/nature20796

Corrected online

28 November 2016

Article tools

Abstract

In tackling the obesity pandemic, significant efforts are devoted to the development of effective weight reduction strategies, yet many dieting individuals fail to maintain a long-term weight reduction, and instead undergo excessive weight regain cycles. The mechanisms driving recurrent post-dieting obesity remain largely elusive. Here, we identify an intestinal microbiome signature that persists after successful dieting of obese mice, which contributes to faster weight regain and metabolic aberrations upon re-exposure to obesity-promoting conditions and transmits the accelerated weight regain phenotype upon inter-animal transfer. We develop a machine-learning algorithm that enables personalized microbiome-based prediction of the extent of post-dieting weight regain. Additionally, we find that the microbiome contributes to diminished post-dieting flavonoid levels and reduced energy expenditure, and demonstrate that flavonoid-based ‘post-biotic’ intervention ameliorates excessive secondary weight gain. Together, our data highlight a possible microbiome contribution to accelerated post-dieting weight regain, and suggest that microbiome-targeting approaches may help to diagnose and treat this common disorder.

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Milestones in Physiology & Discoveries in Medicine and Genomics: Request for Book Review Writing on Amazon.com


physiology-cover-seriese-vol-3individualsaddlebrown-page2

Milestones in Physiology

Discoveries in Medicine, Genomics and Therapeutics

Patient-centric Perspective 

http://www.amazon.com/dp/B019VH97LU 

2015

 

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Preface

Introduction 

Chapter 1: Evolution of the Foundation for Diagnostics and Pharmaceuticals Industries

1.1  Outline of Medical Discoveries between 1880 and 1980

1.2 The History of Infectious Diseases and Epidemiology in the late 19th and 20th Century

1.3 The Classification of Microbiota

1.4 Selected Contributions to Chemistry from 1880 to 1980

1.5 The Evolution of Clinical Chemistry in the 20th Century

1.6 Milestones in the Evolution of Diagnostics in the US HealthCare System: 1920s to Pre-Genomics

 

Chapter 2. The search for the evolution of function of proteins, enzymes and metal catalysts in life processes

2.1 The life and work of Allan Wilson
2.2  The  evolution of myoglobin and hemoglobin
2.3  More complexity in proteins evolution
2.4  Life on earth is traced to oxygen binding
2.5  The colors of life function
2.6  The colors of respiration and electron transport
2.7  Highlights of a green evolution

 

Chapter 3. Evolution of New Relationships in Neuroendocrine States
3.1 Pituitary endocrine axis
3.2 Thyroid function
3.3 Sex hormones
3.4 Adrenal Cortex
3.5 Pancreatic Islets
3.6 Parathyroids
3.7 Gastointestinal hormones
3.8 Endocrine action on midbrain
3.9 Neural activity regulating endocrine response

3.10 Genomic Promise for Neurodegenerative Diseases, Dementias, Autism Spectrum, Schizophrenia, and Serious Depression

 

Chapter 4.  Problems of the Circulation, Altitude, and Immunity

4.1 Innervation of Heart and Heart Rate
4.2 Action of hormones on the circulation
4.3 Allogeneic Transfusion Reactions
4.4 Graft-versus Host reaction
4.5 Unique problems of perinatal period
4.6. High altitude sickness
4.7 Deep water adaptation
4.8 Heart-Lung-and Kidney
4.9 Acute Lung Injury

4.10 Reconstruction of Life Processes requires both Genomics and Metabolomics to explain Phenotypes and Phylogenetics

 

Chapter 5. Problems of Diets and Lifestyle Changes

5.1 Anorexia nervosa
5.2 Voluntary and Involuntary S-insufficiency
5.3 Diarrheas – bacterial and nonbacterial
5.4 Gluten-free diets
5.5 Diet and cholesterol
5.6 Diet and Type 2 diabetes mellitus
5.7 Diet and exercise
5.8 Anxiety and quality of Life
5.9 Nutritional Supplements

 

Chapter 6. Advances in Genomics, Therapeutics and Pharmacogenomics

6.1 Natural Products Chemistry

6.2 The Challenge of Antimicrobial Resistance

6.3 Viruses, Vaccines and immunotherapy

6.4 Genomics and Metabolomics Advances in Cancer

6.5 Proteomics – Protein Interaction

6.6 Pharmacogenomics

6.7 Biomarker Guided Therapy

6.8 The Emergence of a Pharmaceutical Industry in the 20th Century: Diagnostics Industry and Drug Development in the Genomics Era: Mid 80s to Present

6.09 The Union of Biomarkers and Drug Development

6.10 Proteomics and Biomarker Discovery

6.11 Epigenomics and Companion Diagnostics

 

Chapter  7

Integration of Physiology, Genomics and Pharmacotherapy

7.1 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

7.2 Calcium Cycling (ATPase Pump) in Cardiac Gene Therapy: Inhalable Gene Therapy for Pulmonary Arterial Hypertension and Percutaneous Intra-coronary Artery Infusion for Heart Failure: Contributions by Roger J. Hajjar, MD

7.3 Diagnostics and Biomarkers: Novel Genomics Industry Trends vs Present Market Conditions and Historical Scientific Leaders Memoirs

7.4 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

7.5 Diagnosing Diseases & Gene Therapy: Precision Genome Editing and Cost-effective microRNA Profiling

7.6 Imaging Biomarker for Arterial Stiffness: Pathways in Pharmacotherapy for Hypertension and Hypercholesterolemia Management

7.7 Neuroprotective Therapies: Pharmacogenomics vs Psychotropic drugs and Cholinesterase Inhibitors

7.8 Metabolite Identification Combining Genetic and Metabolic Information: Genetic association links unknown metabolites to functionally related genes

7.9 Preserved vs Reduced Ejection Fraction: Available and Needed Therapies

7.10 Biosimilars: Intellectual Property Creation and Protection by Pioneer and by

7.11 Demonstrate Biosimilarity: New FDA Biosimilar Guidelines

 

Chapter 7.  Biopharma Today

8.1 A Great University engaged in Drug Discovery: University of Pittsburgh

8.2 Introduction – The Evolution of Cancer Therapy and Cancer Research: How We Got Here?

8.3 Predicting Tumor Response, Progression, and Time to Recurrence

8.4 Targeting Untargetable Proto-Oncogenes

8.5 Innovation: Drug Discovery, Medical Devices and Digital Health

8.6 Cardiotoxicity and Cardiomyopathy Related to Drugs Adverse Effects

8.7 Nanotechnology and Ocular Drug Delivery: Part I

8.8 Transdermal drug delivery (TDD) system and nanotechnology: Part II

8.9 The Delicate Connection: IDO (Indolamine 2, 3 dehydrogenase) and Cancer Immunology

8.10 Natural Drug Target Discovery and Translational Medicine in Human Microbiome

8.11 From Genomics of Microorganisms to Translational Medicine

8.12 Confined Indolamine 2, 3 dioxygenase (IDO) Controls the Homeostasis of Immune Responses for Good and Bad

 

Chapter 9. BioPharma – Future Trends

9.1 Artificial Intelligence Versus the Scientist: Who Will Win?

9.2 The Vibrant Philly Biotech Scene: Focus on KannaLife Sciences and the Discipline and Potential of Pharmacognosy

9.3 The Vibrant Philly Biotech Scene: Focus on Computer-Aided Drug Design and Gfree Bio, LLC

9.4 Heroes in Medical Research: The Postdoctoral Fellow

9.5 NIH Considers Guidelines for CAR-T therapy: Report from Recombinant DNA Advisory Committee

9.6 1st Pitch Life Science- Philadelphia- What VCs Really Think of your Pitch

9.7 Multiple Lung Cancer Genomic Projects Suggest New Targets, Research Directions for Non-Small Cell Lung Cancer

9.8 Heroes in Medical Research: Green Fluorescent Protein and the Rough Road in Science

9.9 Issues in Personalized Medicine in Cancer: Intratumor Heterogeneity and Branched Evolution Revealed by Multiregion Sequencing

9.10 The SCID Pig II: Researchers Develop Another SCID Pig, And Another Great Model For Cancer Research

Epilogue

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metabolomics-seriesdindividualred-page2

Metabolic Genomics & Pharmaceutics

2015

http://www.amazon.com/dp/B012BB0ZF0

 

Author, Curator and Editor

Larry H Bernstein, MD, FCAP

Chief Scientific Officer

Leaders in Pharmaceutical Business Intelligence

Larry.bernstein@gmail.com

Chapter 1: Metabolic Pathways

1.1            Carbohydrate Metabolism

1.2            Studies of Respiration Lead to Acetyl CoA

1.3            Pentose Shunt, Electron Transfer, Galactose, more Lipids in brief

1.4            The Multi-step Transfer of Phosphate Bond and Hydrogen Exchange Energy

1.5            Diabetes Mellitus

1.6            Glycosaminoglycans, Mucopolysaccharides, L-iduronidase, Enzyme Therapy

Chapter 2: Lipid Metabolism

2.1            Lipid Classification System

2.2            Essential Fatty Acids

2.3            Lipid Oxidation and Synthesis of Fatty Acids

2.4            Cholesterol and Regulation of Liver Synthetic Pathways

2.5            Sex hormones, Adrenal cortisol, Prostaglandins

2.6            Cytoskeleton and Cell Membrane Physiology

2.7            Pharmacological Action of Steroid hormone

Chapter 3: Cell Signaling

3.1            Signaling and Signaling Pathways

3.2            Signaling Transduction Tutorial

3.3            Selected References to Signaling and Metabolic Pathways in Leaders in Pharmaceutical Intelligence

3.4            Integrins, Cadherins, Signaling and the Cytoskeleton

3.5            Complex Models of Signaling: Therapeutic Implications

3.6            Functional Correlates of Signaling Pathways

Chapter 4: Protein Synthesis and Degradation

4.1            The Role and Importance of Transcription Factors

4.2            RNA and the Transcription of the Genetic Code

4.3            9:30 – 10:00, 6/13/2014, David Bartel “MicroRNAs, Poly(A) tails and Post-transcriptional Gene Regulation

4.4            Transcriptional Silencing and Longevity Protein Sir2

4.5            Ca2+ Signaling: Transcriptional Control

4.6            Long Noncoding RNA Network regulates PTEN Transcription

4.7            Zinc-Finger Nucleases (ZFNs) and Transcription Activator–Like Effector Nucleases (TALENs)

4.8            Cardiac Ca2+ Signaling: Transcriptional Control

4.9            Transcription Factor Lyl-1 Critical in Producing Early T-Cell Progenitors

4.10            Human Frontal Lobe Brain: Specific Transcriptional Networks

4.11            Somatic, Germ-cell, and Whole Sequence DNA in Cell Lineage and Disease

Chapter 5:  Sub-cellular Structure

5.1            Mitochondria: Origin from Oxygen free environment, Role in Aerobic Glycolysis and Metabolic Adaptation

5.2            Mitochondrial Metabolism and Cardiac Function

5.3            Mitochondria: More than just the “Powerhouse of the Cell”

5.4            Mitochondrial Fission and Fusion: Potential Therapeutic Targets?

5.5            Mitochondrial Mutation Analysis might be “1-step” Away

5.6            Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy: Commentary of Bioinformatics Approaches

5.7            Chromatophagy, A New Cancer Therapy: Starve The Diseased Cell Until It Eats Its Own DNA

5.8           A Curated Census of Autophagy-Modulating Proteins and Small Molecules Candidate Targets for Cancer Therapy

5.9           Role of Calcium, the Actin Skeleton, and Lipid Structures in Signaling and Cell Motility

Chapter 6: Proteomics

6.1            Proteomics, Metabolomics, Signaling Pathways, and Cell Regulation: a Compilation of Articles in the Journal http://pharmaceuticalintelligence.com

6.2            A Brief Curation of Proteomics, Metabolomics, and Metabolism

6.3            Using RNA-seq and Targeted Nucleases to Identify Mechanisms of Drug Resistance in Acute Myeloid Leukemia, SK Rathe in Nature, 2014

6.4            Proteomics – The Pathway to Understanding and Decision-making in Medicine

6.5            Advances in Separations Technology for the “OMICs” and Clarification of Therapeutic Targets

6.6           Expanding the Genetic Alphabet and Linking the Genome to the Metabolome

6.7            Genomics, Proteomics and Standards

6.8            Proteins and Cellular Adaptation to Stress

6.9            Genes, Proteomes, and their Interaction

6.10           Regulation of Somatic Stem Cell Function

6.11           Scientists discover that Pluripotency factor NANOG is also active in Adult Organism

Chapter 7: Metabolomics

7.1            Extracellular Evaluation of Intracellular Flux in Yeast Cells

7.2            Metabolomic Analysis of Two Leukemia Cell Lines Part I

7.3            Metabolomic Analysis of Two Leukemia Cell Lines Part II

7.4            Buffering of Genetic Modules involved in Tricarboxylic Acid Cycle Metabolism provides Homeomeostatic Regulation

7.5            Metabolomics, Metabonomics and Functional Nutrition: The Next Step in Nutritional Metabolism and Biotherapeutics

7.6            Isoenzymes in Cell Metabolic Pathways

7.7            A Brief Curation of Proteomics, Metabolomics, and Metabolism

7.8            Metabolomics is about Metabolic Systems Integration

7.9             Mechanisms of Drug Resistance

7.10           Development Of Super-Resolved Fluorescence Microscopy

7.11            Metabolic Reactions Need Just Enough

Chapter 8.  Impairments in Pathological States: Endocrine Disorders; Stress Hypermetabolism and CAncer

8.1           Omega3 Fatty Acids, Depleting the Source, and Protein Insufficiency in Renal Disease

8.2             Liver Endoplasmic Reticulum Stress and Hepatosteatosis

8.3            How Methionine Imbalance with Sulfur Insufficiency Leads to Hyperhomocysteinemia

8.4            AMPK Is a Negative Regulator of the Warburg Effect and Suppresses Tumor Growth InVivo

8.5           A Second Look at the Transthyretin Nutrition Inflammatory Conundrum

8.6            Mitochondrial Damage and Repair under Oxidative Stress

8.7            Metformin, Thyroid Pituitary Axis, Diabetes Mellitus, and Metabolism

8.8            Is the Warburg Effect the Cause or the Effect of Cancer: A 21st Century View?

8.9            Social Behavior Traits Embedded in Gene Expression

8.10          A Future for Plasma Metabolomics in Cardiovascular Disease Assessment

Chapter 9: Genomic Expression in Health and Disease 

9.1            Genetics of Conduction Disease: Atrioventricular (AV) Conduction Disease (block): Gene Mutations – Transcription, Excitability, and Energy Homeostasis

9.2            BRCA1 a Tumour Suppressor in Breast and Ovarian Cancer – Functions in Transcription, Ubiquitination and DNA Repair

9.3            Metabolic Drivers in Aggressive Brain Tumors

9.4            Modified Yeast Produces a Range of Opiates for the First time

9.5            Parasitic Plant Strangleweed Injects Host With Over 9,000 RNA Transcripts

9.6            Plant-based Nutrition, Neutraceuticals and Alternative Medicine: Article Compilation the Journal

9.7            Reference Genes in the Human Gut Microbiome: The BGI Catalogue

9.8            Two Mutations, in the PCSK9 Gene: Eliminates a Protein involved in Controlling LDL Cholesterol

9.9            HDL-C: Target of Therapy – Steven E. Nissen, MD, MACC, Cleveland Clinic vs Peter Libby, MD, BWH

Summary 

Epilogue


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Keystone Symposia on Molecular and Cellular Biology – 2016-2017 Forthcoming Conferences in Life Sciences

Reporter: Aviva Lev-Ari, PhD, RN

2016-2017 Forthcoming Conferences in Life Sciences by topic:

DNA Replication and Recombination (Z2)
April 2 – 6, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: John F.X. Diffley, Anja Groth and Scott Keeney

Immunology

Translational Vaccinology for Global Health (S1)
October 25 – 29, 2016 | London, United Kingdom
Scientific Organizers: Christopher L. Karp, Gagandeep Kang and Rino Rappuoli

Hemorrhagic Fever Viruses (S3)
December 4 – 8, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: William E. Dowling and Thomas W. Geisbert

Cell Plasticity within the Tumor Microenvironment (A1)
January 8 – 12, 2017 | Big Sky, Montana, USA
Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad

TGF-ß in Immunity, Inflammation and Cancer (A3)
January 9 – 13, 2017 | Taos, New Mexico, USA
Scientific Organizers: Wanjun Chen, Joanne E. Konkel and Richard A. Flavell

New Developments in Our Basic Understanding of Tuberculosis (A5)
January 14 – 18, 2017 | Vancouver, British Columbia, Canada
Scientific Organizers: Samuel M. Behar and Valerie Mizrahi

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)
January 19 – 23, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. Cosulich

Biobetters and Next-Generation Biologics: Innovative Strategies for Optimally Effective Therapies (A7)
January 22 – 26, 2017 | Snowbird, Utah, USA
Scientific Organizers: Cherié L. Butts, Amy S. Rosenberg, Amy D. Klion and Sachdev S. Sidhu

Obesity and Adipose Tissue Biology (J4)
January 22 – 26, 2017 | Keystone, Colorado, USA
Scientific Organizers: Marc L. Reitman, Ruth E. Gimeno and Jan Nedergaard

Inflammation-Driven Cancer: Mechanisms to Therapy (J7)
February 5 – 9, 2017 | Keystone, Colorado, USA
Scientific Organizers: Fiona M. Powrie, Michael Karin and Alberto Mantovani

Autophagy Network Integration in Health and Disease (B2)
February 12 – 16, 2017 | Copper Mountain, Colorado, USA
Scientific Organizers: Ivan Dikic, Katja Simon and J. Wade Harper

Asthma: From Pathway Biology to Precision Therapeutics (B3)
February 12 – 16, 2017 | Keystone, Colorado, USA
Scientific Organizers: Clare M. Lloyd, John V. Fahy and Sally Wenzel-Morganroth

Viral Immunity: Mechanisms and Consequences (B4)
February 19 – 23, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Akiko Iwasaki, Daniel B. Stetson and E. John Wherry

Lipidomics and Bioactive Lipids in Metabolism and Disease (B6)
February 26 – March 2, 2017 | Tahoe City, California, USA
Scientific Organizers: Alfred H. Merrill, Walter Allen Shaw, Sarah Spiegel and Michael J.O.Wakelam

Bile Acid Receptors as Signal Integrators in Liver and Metabolism (C1)
March 3 – 7, 2017 | Monterey, California, USA
Scientific Organizers: Luciano Adorini, Kristina Schoonjans and Scott L. Friedman

Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology (C7)
March 19 – 23, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: Robert D. Schreiber, James P. Allison, Philip D. Greenberg and Glenn Dranoff

Pattern Recognition Signaling: From Innate Immunity to Inflammatory Disease (X5)
March 19 – 23, 2017 | Banff, Alberta, Canada
Scientific Organizers: Thirumala-Devi Kanneganti, Vishva M. Dixit and Mohamed Lamkanfi

Type I Interferon: Friend and Foe Alike (X6)
March 19 – 23, 2017 | Banff, Alberta, Canada
Scientific Organizers: Alan Sher, Virginia Pascual, Adolfo García-Sastre and Anne O’Garra

Injury, Inflammation and Fibrosis (C8)
March 26 – 30, 2017 | Snowbird, Utah, USA
Scientific Organizers: Tatiana Kisseleva, Michael Karin and Andrew M. Tager

Immune Regulation in Autoimmunity and Cancer (D1)
March 26 – 30, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: David A. Hafler, Vijay K. Kuchroo and Jane L. Grogan

B Cells and T Follicular Helper Cells – Controlling Long-Lived Immunity (D2)
April 23 – 27, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: Stuart G. Tangye, Ignacio Sanz and Hai Qi

Mononuclear Phagocytes in Health, Immune Defense and Disease (D3)
April 30 – May 4, 2017 | Austin, Texas, USA
Scientific Organizers: Steffen Jung and Miriam Merad

Modeling Viral Infections and Immunity (E1)
May 1 – 4, 2017 | Estes Park, Colorado, USA
Scientific Organizers: Alan S. Perelson, Rob J. De Boer and Phillip D. Hodgkin

Integrating Metabolism and Immunity (E4)
May 29 – June 2, 2017 | Dublin, Ireland
Scientific Organizers: Hongbo Chi, Erika L. Pearce, Richard A. Flavell and Luke A.J. O’Neill

Neuroinflammation: Concepts, Characteristics, Consequences (E5)
June 19 – 23, 2017 | Keystone, Colorado, USA
Scientific Organizers: Richard M. Ransohoff, Christopher K. Glass and V. Hugh Perry

Infectious Diseases

Translational Vaccinology for Global Health (S1)
October 25 – 29, 2016 | London, United Kingdom
Scientific Organizers: Christopher L. Karp, Gagandeep Kang and Rino Rappuoli

Hemorrhagic Fever Viruses (S3)
December 4 – 8, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: William E. Dowling and Thomas W. Geisbert

Cellular Stress Responses and Infectious Agents (S4)
December 4 – 8, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: Margo A. Brinton, Sandra K. Weller and Beth Levine

New Developments in Our Basic Understanding of Tuberculosis (A5)
January 14 – 18, 2017 | Vancouver, British Columbia, Canada
Scientific Organizers: Samuel M. Behar and Valerie Mizrahi

Autophagy Network Integration in Health and Disease (B2)
February 12 – 16, 2017 | Copper Mountain, Colorado, USA
Scientific Organizers: Ivan Dikic, Katja Simon and J. Wade Harper

Viral Immunity: Mechanisms and Consequences (B4)
February 19 – 23, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Akiko Iwasaki, Daniel B. Stetson and E. John Wherry

Malaria: From Innovation to Eradication (B5)
February 19 – 23, 2017 | Kampala, Uganda
Scientific Organizers: Marcel Tanner, Sarah K. Volkman, Marcus V.G. Lacerda and Salim Abdulla

Type I Interferon: Friend and Foe Alike (X6)
March 19 – 23, 2017 | Banff, Alberta, Canada
Scientific Organizers: Alan Sher, Virginia Pascual, Adolfo García-Sastre and Anne O’Garra

HIV Vaccines (C9)
March 26 – 30, 2017 | Steamboat Springs, Colorado, USA
Scientific Organizers: Andrew B. Ward, Penny L. Moore and Robin Shattock

Modeling Viral Infections and Immunity (E1)
May 1 – 4, 2017 | Estes Park, Colorado, USA
Scientific Organizers: Alan S. Perelson, Rob J. De Boer and Phillip D. Hodgkin

Metabolic Diseases

Mitochondria Communication (A4)
January 14 – 18, 2017 | Taos, New Mexico, USA
Scientific Organizers: Jared Rutter, Cole M. Haynes and Marcia C. Haigis

Diabetes (J3)
January 22 – 26, 2017 | Keystone, Colorado, USA
Scientific Organizers: Jiandie Lin, Clay F. Semenkovich and Rohit N. Kulkarni

Obesity and Adipose Tissue Biology (J4)
January 22 – 26, 2017 | Keystone, Colorado, USA
Scientific Organizers: Marc L. Reitman, Ruth E. Gimeno and Jan Nedergaard

Microbiome in Health and Disease (J8)
February 5 – 9, 2017 | Keystone, Colorado, USA
Scientific Organizers: Julie A. Segre, Ramnik Xavier and William Michael Dunne

Bile Acid Receptors as Signal Integrators in Liver and Metabolism (C1)
March 3 – 7, 2017 | Monterey, California, USA
Scientific Organizers: Luciano Adorini, Kristina Schoonjans and Scott L. Friedman

Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity (C6)
March 19 – 22, 2017 | Tahoe City, California, USA
Scientific Organizers: Franck Mauvais-Jarvis, Deborah Clegg and Arthur P. Arnold

Neuronal Control of Appetite, Metabolism and Weight (Z5)
May 9 – 13, 2017 | Copenhagen, Denmark
Scientific Organizers: Lora K. Heisler and Scott M. Sternson

Gastrointestinal Control of Metabolism (Z6)
May 9 – 13, 2017 | Copenhagen, Denmark
Scientific Organizers: Randy J. Seeley, Matthias H. Tschöp and Fiona M. Gribble

Integrating Metabolism and Immunity (E4)
May 29 – June 2, 2017 | Dublin, Ireland
Scientific Organizers: Hongbo Chi, Erika L. Pearce, Richard A. Flavell and Luke A.J. O’Neill

Neurobiology

Transcriptional and Epigenetic Control in Stem Cells (J1)
January 8 – 12, 2017 | Olympic Valley, California, USA
Scientific Organizers: Konrad Hochedlinger, Kathrin Plath and Marius Wernig

Neurogenesis during Development and in the Adult Brain (J2)
January 8 – 12, 2017 | Olympic Valley, California, USA
Scientific Organizers: Alysson R. Muotri, Kinichi Nakashima and Xinyu Zhao

Rare and Undiagnosed Diseases: Discovery and Models of Precision Therapy (C2)
March 5 – 8, 2017 | Boston, Massachusetts, USA
Scientific Organizers: William A. Gahl and Christoph Klein

mRNA Processing and Human Disease (C3)
March 5 – 8, 2017 | Taos, New Mexico, USA
Scientific Organizers: James L. Manley, Siddhartha Mukherjee and Gideon Dreyfuss

Synapses and Circuits: Formation, Function, and Dysfunction (X1)
March 5 – 8, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Tony Koleske, Yimin Zou, Kristin Scott and A. Kimberley McAllister

Connectomics (X2)
March 5 – 8, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Olaf Sporns, Danielle Bassett and Jeremy Freeman

Neuronal Control of Appetite, Metabolism and Weight (Z5)
May 9 – 13, 2017 | Copenhagen, Denmark
Scientific Organizers: Lora K. Heisler and Scott M. Sternson

Neuroinflammation: Concepts, Characteristics, Consequences (E5)
June 19 – 23, 2017 | Keystone, Colorado, USA
Scientific Organizers: Richard M. Ransohoff, Christopher K. Glass and V. Hugh Perry

Plant Biology

Phytobiomes: From Microbes to Plant Ecosystems (S2)
November 8 – 12, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: Jan E. Leach, Kellye A. Eversole, Jonathan A. Eisen and Gwyn Beattie

Structural Biology

Frontiers of NMR in Life Sciences (C5)
March 12 – 16, 2017 | Keystone, Colorado, USA
Scientific Organizers: Kurt Wüthrich, Michael Sattler and Stephen W. Fesik

Technologies

Cell Plasticity within the Tumor Microenvironment (A1)
January 8 – 12, 2017 | Big Sky, Montana, USA
Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad

Precision Genome Engineering (A2)
January 8 – 12, 2017 | Breckenridge, Colorado, USA
Scientific Organizers: J. Keith Joung, Emmanuelle Charpentier and Olivier Danos

Transcriptional and Epigenetic Control in Stem Cells (J1)
January 8 – 12, 2017 | Olympic Valley, California, USA
Scientific Organizers: Konrad Hochedlinger, Kathrin Plath and Marius Wernig

Protein-RNA Interactions: Scale, Mechanisms, Structure and Function of Coding and Noncoding RNPs (J6)
February 5 – 9, 2017 | Banff, Alberta, Canada
Scientific Organizers: Gene W. Yeo, Jernej Ule, Karla Neugebauer and Melissa J. Moore

Lipidomics and Bioactive Lipids in Metabolism and Disease (B6)
February 26 – March 2, 2017 | Tahoe City, California, USA
Scientific Organizers: Alfred H. Merrill, Walter Allen Shaw, Sarah Spiegel and Michael J.O.Wakelam

Connectomics (X2)
March 5 – 8, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Olaf Sporns, Danielle Bassett and Jeremy Freeman

Engineered Cells and Tissues as Platforms for Discovery and Therapy (K1)
March 9 – 12, 2017 | Boston, Massachusetts, USA
Scientific Organizers: Laura E. Niklason, Milica Radisic and Nenad Bursac

Frontiers of NMR in Life Sciences (C5)
March 12 – 16, 2017 | Keystone, Colorado, USA
Scientific Organizers: Kurt Wüthrich, Michael Sattler and Stephen W. Fesik

October 2016

Translational Vaccinology for Global Health (S1)
October 25 – 29, 2016 | London, United Kingdom
Scientific Organizers: Christopher L. Karp, Gagandeep Kang and Rino Rappuoli

November 2016

Phytobiomes: From Microbes to Plant Ecosystems (S2)
November 8 – 12, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: Jan E. Leach, Kellye A. Eversole, Jonathan A. Eisen and Gwyn Beattie

December 2016

Hemorrhagic Fever Viruses (S3)
December 4 – 8, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: William E. Dowling and Thomas W. Geisbert

Cellular Stress Responses and Infectious Agents (S4)
December 4 – 8, 2016 | Santa Fe, New Mexico, USA
Scientific Organizers: Margo A. Brinton, Sandra K. Weller and Beth Levine

January 2017

Cell Plasticity within the Tumor Microenvironment (A1)
January 8 – 12, 2017 | Big Sky, Montana, USA
Scientific Organizers: Sergei Grivennikov, Florian R. Greten and Mikala Egeblad

Precision Genome Engineering (A2)
January 8 – 12, 2017 | Breckenridge, Colorado, USA
Scientific Organizers: J. Keith Joung, Emmanuelle Charpentier and Olivier Danos

Transcriptional and Epigenetic Control in Stem Cells (J1)
January 8 – 12, 2017 | Olympic Valley, California, USA
Scientific Organizers: Konrad Hochedlinger, Kathrin Plath and Marius Wernig

Neurogenesis during Development and in the Adult Brain (J2)
January 8 – 12, 2017 | Olympic Valley, California, USA
Scientific Organizers: Alysson R. Muotri, Kinichi Nakashima and Xinyu Zhao

TGF-ß in Immunity, Inflammation and Cancer (A3)
January 9 – 13, 2017 | Taos, New Mexico, USA
Scientific Organizers: Wanjun Chen, Joanne E. Konkel and Richard A. Flavell

Mitochondria Communication (A4)
January 14 – 18, 2017 | Taos, New Mexico, USA
Scientific Organizers: Jared Rutter, Cole M. Haynes and Marcia C. Haigis

New Developments in Our Basic Understanding of Tuberculosis (A5)
January 14 – 18, 2017 | Vancouver, British Columbia, Canada
Scientific Organizers: Samuel M. Behar and Valerie Mizrahi

PI3K Pathways in Immunology, Growth Disorders and Cancer (A6)
January 19 – 23, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Leon O. Murphy, Klaus Okkenhaug and Sabina C. Cosulich

Biobetters and Next-Generation Biologics: Innovative Strategies for Optimally Effective Therapies (A7)
January 22 – 26, 2017 | Snowbird, Utah, USA
Scientific Organizers: Cherié L. Butts, Amy S. Rosenberg, Amy D. Klion and Sachdev S. Sidhu

Diabetes (J3)
January 22 – 26, 2017 | Keystone, Colorado, USA
Scientific Organizers: Jiandie Lin, Clay F. Semenkovich and Rohit N. Kulkarni

Obesity and Adipose Tissue Biology (J4)
January 22 – 26, 2017 | Keystone, Colorado, USA
Scientific Organizers: Marc L. Reitman, Ruth E. Gimeno and Jan Nedergaard

Omics Strategies to Study the Proteome (A8)
January 29 – February 2, 2017 | Breckenridge, Colorado, USA
Scientific Organizers: Alan Saghatelian, Chuan He and Ileana M. Cristea

Epigenetics and Human Disease: Progress from Mechanisms to Therapeutics (A9)
January 29 – February 2, 2017 | Seattle, Washington, USA
Scientific Organizers: Johnathan R. Whetstine, Jessica K. Tyler and Rab K. Prinjha

Hematopoiesis (B1)
January 31 – February 4, 2017 | Banff, Alberta, Canada
Scientific Organizers: Catriona H.M. Jamieson, Andreas Trumpp and Paul S. Frenette

February 2017

Noncoding RNAs: From Disease to Targeted Therapeutics (J5)
February 5 – 9, 2017 | Banff, Alberta, Canada
Scientific Organizers: Kevin V. Morris, Archa Fox and Paloma Hoban Giangrande

Protein-RNA Interactions: Scale, Mechanisms, Structure and Function of Coding and Noncoding RNPs (J6)
February 5 – 9, 2017 | Banff, Alberta, Canada
Scientific Organizers: Gene W. Yeo, Jernej Ule, Karla Neugebauer and Melissa J. Moore

Inflammation-Driven Cancer: Mechanisms to Therapy (J7)
February 5 – 9, 2017 | Keystone, Colorado, USA
Scientific Organizers: Fiona M. Powrie, Michael Karin and Alberto Mantovani

Microbiome in Health and Disease (J8)
February 5 – 9, 2017 | Keystone, Colorado, USA
Scientific Organizers: Julie A. Segre, Ramnik Xavier and William Michael Dunne

Autophagy Network Integration in Health and Disease (B2)
February 12 – 16, 2017 | Copper Mountain, Colorado, USA
Scientific Organizers: Ivan Dikic, Katja Simon and J. Wade Harper

Asthma: From Pathway Biology to Precision Therapeutics (B3)
February 12 – 16, 2017 | Keystone, Colorado, USA
Scientific Organizers: Clare M. Lloyd, John V. Fahy and Sally Wenzel-Morganroth

Viral Immunity: Mechanisms and Consequences (B4)
February 19 – 23, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Akiko Iwasaki, Daniel B. Stetson and E. John Wherry

Malaria: From Innovation to Eradication (B5)
February 19 – 23, 2017 | Kampala, Uganda
Scientific Organizers: Marcel Tanner, Sarah K. Volkman, Marcus V.G. Lacerda and Salim Abdulla

Lipidomics and Bioactive Lipids in Metabolism and Disease (B6)
February 26 – March 2, 2017 | Tahoe City, California, USA
Scientific Organizers: Alfred H. Merrill, Walter Allen Shaw, Sarah Spiegel and Michael J.O.Wakelam

March 2017

Bile Acid Receptors as Signal Integrators in Liver and Metabolism (C1)
March 3 – 7, 2017 | Monterey, California, USA
Scientific Organizers: Luciano Adorini, Kristina Schoonjans and Scott L. Friedman

Rare and Undiagnosed Diseases: Discovery and Models of Precision Therapy (C2)
March 5 – 8, 2017 | Boston, Massachusetts, USA
Scientific Organizers: William A. Gahl and Christoph Klein

mRNA Processing and Human Disease (C3)
March 5 – 8, 2017 | Taos, New Mexico, USA
Scientific Organizers: James L. Manley, Siddhartha Mukherjee and Gideon Dreyfuss

Kinases: Next-Generation Insights and Approaches (C4)
March 5 – 9, 2017 | Breckenridge, Colorado, USA
Scientific Organizers: Reid M. Huber, John Kuriyan and Ruth H. Palmer

Synapses and Circuits: Formation, Function, and Dysfunction (X1)
March 5 – 8, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Tony Koleske, Yimin Zou, Kristin Scott and A. Kimberley McAllister

Connectomics (X2)
March 5 – 8, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Olaf Sporns, Danielle Bassett and Jeremy Freeman

Tumor Metabolism: Mechanisms and Targets (X3)
March 5 – 9, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: Brendan D. Manning, Kathryn E. Wellen and Reuben J. Shaw

Adaptations to Hypoxia in Physiology and Disease (X4)
March 5 – 9, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: M. Celeste Simon, Amato J. Giaccia and Randall S. Johnson

Engineered Cells and Tissues as Platforms for Discovery and Therapy (K1)
March 9 – 12, 2017 | Boston, Massachusetts, USA
Scientific Organizers: Laura E. Niklason, Milica Radisic and Nenad Bursac

Frontiers of NMR in Life Sciences (C5)
March 12 – 16, 2017 | Keystone, Colorado, USA
Scientific Organizers: Kurt Wüthrich, Michael Sattler and Stephen W. Fesik

Sex and Gender Factors Affecting Metabolic Homeostasis, Diabetes and Obesity (C6)
March 19 – 22, 2017 | Tahoe City, California, USA
Scientific Organizers: Franck Mauvais-Jarvis, Deborah Clegg and Arthur P. Arnold

Cancer Immunology and Immunotherapy: Taking a Place in Mainstream Oncology (C7)
March 19 – 23, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: Robert D. Schreiber, James P. Allison, Philip D. Greenberg and Glenn Dranoff

Pattern Recognition Signaling: From Innate Immunity to Inflammatory Disease (X5)
March 19 – 23, 2017 | Banff, Alberta, Canada
Scientific Organizers: Thirumala-Devi Kanneganti, Vishva M. Dixit and Mohamed Lamkanfi

Type I Interferon: Friend and Foe Alike (X6)
March 19 – 23, 2017 | Banff, Alberta, Canada
Scientific Organizers: Alan Sher, Virginia Pascual, Adolfo García-Sastre and Anne O’Garra

Injury, Inflammation and Fibrosis (C8)
March 26 – 30, 2017 | Snowbird, Utah, USA
Scientific Organizers: Tatiana Kisseleva, Michael Karin and Andrew M. Tager

HIV Vaccines (C9)
March 26 – 30, 2017 | Steamboat Springs, Colorado, USA
Scientific Organizers: Andrew B. Ward, Penny L. Moore and Robin Shattock

Immune Regulation in Autoimmunity and Cancer (D1)
March 26 – 30, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: David A. Hafler, Vijay K. Kuchroo and Jane L. Grogan

Molecular Mechanisms of Heart Development (X7)
March 26 – 30, 2017 | Keystone, Colorado, USA
Scientific Organizers: Benoit G. Bruneau, Brian L. Black and Margaret E. Buckingham

RNA-Based Approaches in Cardiovascular Disease (X8)
March 26 – 30, 2017 | Keystone, Colorado, USA
Scientific Organizers: Thomas Thum and Roger J. Hajjar

April 2017

Genomic Instability and DNA Repair (Z1)
April 2 – 6, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Julia Promisel Cooper, Marco F. Foiani and Geneviève Almouzni

DNA Replication and Recombination (Z2)
April 2 – 6, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: John F.X. Diffley, Anja Groth and Scott Keeney

B Cells and T Follicular Helper Cells – Controlling Long-Lived Immunity (D2)
April 23 – 27, 2017 | Whistler, British Columbia, Canada
Scientific Organizers: Stuart G. Tangye, Ignacio Sanz and Hai Qi

Mononuclear Phagocytes in Health, Immune Defense and Disease (D3)
April 30 – May 4, 2017 | Austin, Texas, USA
Scientific Organizers: Steffen Jung and Miriam Merad

May 2017

Modeling Viral Infections and Immunity (E1)
May 1 – 4, 2017 | Estes Park, Colorado, USA
Scientific Organizers: Alan S. Perelson, Rob J. De Boer and Phillip D. Hodgkin

Angiogenesis and Vascular Disease (Z3)
May 8 – 12, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: M. Luisa Iruela-Arispe, Timothy T. Hla and Courtney Griffin

Mitochondria, Metabolism and Heart (Z4)
May 8 – 12, 2017 | Santa Fe, New Mexico, USA
Scientific Organizers: Junichi Sadoshima, Toren Finkel and Åsa B. Gustafsson

Neuronal Control of Appetite, Metabolism and Weight (Z5)
May 9 – 13, 2017 | Copenhagen, Denmark
Scientific Organizers: Lora K. Heisler and Scott M. Sternson

Gastrointestinal Control of Metabolism (Z6)
May 9 – 13, 2017 | Copenhagen, Denmark
Scientific Organizers: Randy J. Seeley, Matthias H. Tschöp and Fiona M. Gribble

Aging and Mechanisms of Aging-Related Disease (E2)
May 15 – 19, 2017 | Yokohama, Japan
Scientific Organizers: Kazuo Tsubota, Shin-ichiro Imai, Matt Kaeberlein and Joan Mannick

Single Cell Omics (E3)
May 26 – 30, 2017 | Stockholm, Sweden
Scientific Organizers: Sarah Teichmann, Evan W. Newell and William J. Greenleaf

Integrating Metabolism and Immunity (E4)
May 29 – June 2, 2017 | Dublin, Ireland
Scientific Organizers: Hongbo Chi, Erika L. Pearce, Richard A. Flavell and Luke A.J. O’Neill

Cell Death and Inflammation (K2)
May 29 – June 2, 2017 | Dublin, Ireland
Scientific Organizers: Seamus J. Martin and John Silke

June 2017

Neuroinflammation: Concepts, Characteristics, Consequences (E5)
June 19 – 23, 2017 | Keystone, Colorado, USA
Scientific Organizers: Richard M. Ransohoff, Christopher K. Glass and V. Hugh Perry

SOURCE

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Toxicities Associated with Immuno-oncology Treatment

Larry H. Bernstein, MD, FCAP

Curator: LPBI

 

ICLIO: Be Aware of Novel Toxicities With New Ca Drugs  

Advent of new immunotherapies warrants education for non-oncologists

by Eric T. Rosenthal
Special Correspondent, MedPage Today
http://www.medpagetoday.com/HematologyOncology/Chemotherapy/58582

CHICAGO — A new class of cancer immunotherapies, led by pembrolizumab (Keytruda), has taken the oncology world by storm. But with this novel type of treatment comes a new challenge.

The Association of Community Cancer Centers (ACCC) wants to ensure that non-oncologist physicians know how to take care of their patients receiving these agents since doctors in other specialties may not be aware of the side effects related to the immunotherapies.

The initiative is one of the steps taken by the association’s Institute of Clinical Immuno-Oncology’s (ICLIO) in making immunotherapy available in the community.

ICLIO was launched 1 year ago to help prepare community cancer teams and centers to deal with the clinical, coverage, and reimbursement issues related to immunotherapy.

During the American Society of Clinical Oncology annual meeting here MedPage Todayspoke with ACCC President Jennie R. Crews, MD, and ICLIO Chair Lee S. Schwartzberg, MD, about the institute’s growth and future plans.

Schwartzberg, chief of the division of hematology and oncology at the University of Tennessee, as well as executive director of the West Cancer Center in Memphis, said that the field of immunotherapy “is moving so fast that we can’t have enough education.”

“Needs change over time and last year many cancer practices became familiar with immuno-oncology and now we have to go deeper and broader.”

The broadening, he explained, involves educating other medical subspecialists about immune-related toxicities from the new agents.

“The problem is that we see related toxicities that are not managed well, and we’re having trouble with this.”

He cited as two primary examples toxic side effects such as colitis and pneumonitis and the necessity of educating gastroenterologists and pulmonologists about their relationship to immunotherapy.

Many times these subspecialists, as well as dermatologists, endocrinologists, emergency physicians, and internists see autoimmune-related toxicities and first think they are from chemotherapy or infection, according to Schwartzberg.

“But they are going to be going down a very bad path with these patients if they think this way,” noting that a colleague from a leading cancer center had recently mentioned that the institution’s emergency room staff didn’t always understand about immunotherapy reactions.

He said that, although ICLIO does not have direct access to reaching many other subspecialists, it was beginning to develop educational materials that oncologists could share with other medical colleagues, as well as to work with some of the subspecialty societies.

“Education, however, has to be across the board, and has to include patients as well,” he said, adding that many cancer immunotherapy patients were being provided with cards that explained their immunotherapy and could be handed to nurses and physicians at the outset of their medical intervention, saving time and the risk of undergoing the wrong treatment.

In a separate interview, Crews, medical director for Cancer Services PeaceHealth at St. Joseph Medical Center in Bellingham, Wash., said that ACCC members include both academic centers and community practices including both hospital-based and private. (An ACCC public relations representative monitored the interview.)

“We are not focused on what the science is, but rather on how do we take this technology out to the community to bring cancer to where patients are,” she said, adding that she and others are very passionate in the belief that cancer care should be delivered wherever cancer patients live.

She said since ICLIO started in June 2015, much of its infrastructure and programs have been established, including a webinar series, eNewsletters, eLearning Modules, tumor subcommittee working groups, an on-site preceptorship program, an ICLIO stakeholder summit, and an upcoming second national conference this fall in Philadelphia.

That conference will be preceded by a stakeholder summit bringing together providers, patient advocates, payers, pharmaceutical producers, and others, which the ACCC hopes will produce a white paper.

The last year has seen the growth of the initiative’s Scholars Program to about 50 oncologists who have received training through ICLIO’s learning modules.

These scholars will in turn eventually be able to serve as mentors to the 2,000 cancer programs with some 20,000 individual members that make up ACCC’s membership.

Crews said that to date about 700 cancer programs involving some 1,900 individuals have participated in the webinars, and about 100 people attended ICLIO’s first annual conference last October.

She said that in addition to the charitable contribution initially made by Bristol-Myers Squibb last year to help launch ICLIO, Merck has also provided an educational grant, but she would not disclose the amount of the funding.

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