Posts Tagged ‘Weill Cornell Medical College’

New avenues for research in membrane biology reveals the mobility of protein at work

Posted in Cell Biology, cell-based therapy, Medical Devices R&D and Inventions, Medical Imaging Technology, Proteins, tagged Atomic force microscopy, Cell Biology, cryo-electron microscopy, imaging, ion transport, membrane protein, Signal transduction, structural biology, Weill Cornell Medical College, x-ray crystallography on August 23, 2021| Leave a Comment »

New avenues for research in membrane biology reveals the mobility of protein at work

Curator and Reporter: Dr. Premalata Pati, Ph.D., Postdoc

Membrane proteins (MPs) are proteins that exist in the plasma membrane and conduct a variety of biological functions such as ion transport, substrate transport, and signal transduction. MPs undergo function-related conformational changes on time intervals spanning from nanoseconds to seconds. Many MP structures have been solved thanks to recent developments in structural biology, particularly in single-particle cryo-Electron Microscopy (cryo-EM). Obtaining time-resolved dynamic information on MPs in their membrane surroundings, on the other hand, remains a significant difficulty.

OmpG (Open state) in a fully hydrated dimyristoylphosphatidylcholine (DMPC) bilayer. The protein is shown in light green cartoon. Lipids units are depicted in yellow, while their phosphate and choline groups are illustrated as orange and green van der Waals spheres, respectively. Potassium and chloride counterions are shown in green and purple, respectively. A continuous and semi-transparent cyan representation is used for water.
https://static-content.springer.com/esm/art%3A10.1038%2Fs41467-021-24660-1/MediaObjects/41467_2021_24660_MOESM1_ESM.pdf

Weill Cornell Medicine (WCM) researchers have found that they can record high-speed protein movements while linking them to function. The accomplishment should allow scientists to examine proteins in more depth than ever before, and in theory, it should allow for the development of drugs that work better by hitting their protein targets much more effectively.

The researchers utilized High-Speed Atomic Force Microscopy (HS-AFM) to record the rapid motions of a channel protein and published in a report in Nature Communications on July 16. Such proteins generally create channel or tube-like structures in cell membranes, which open to allow molecules to flow under particular conditions. The researchers were able to record the channel protein’s rapid openings and closings with the same temporal resolution as single channel recordings, a typical technique for recording the intermittent passage of charged molecules through the channel.

Senior author Simon Scheuring, professor of physiology and biophysics in anesthesiology at WCM, said,

There has been a significant need for a tool like this that achieves such a high bandwidth that it can ‘see’ the structural variations of molecules as they work.

Researchers can now produce incredibly detailed photographs of molecules using techniques like X-ray crystallography and electron microscopy, showing their structures down to the atomic scale. The average or dominant structural positionings, or conformations, of the molecules, are depicted in these “images,” which are often calculated from thousands of individual photos. In that way, they’re similar to the long-exposure still photos from the dawn of photography.

Many molecules, on the other hand, are flexible and always-moving machinery rather than fixed structures. Scientists need to generate videos, not still photos, to reveal how such molecules move as they work, to see how their motion translates to function to catch their critical functional conformations, which may only exist for a brief moment. Current techniques for dynamic structural imaging, on the other hand, have several drawbacks, one of which being the requirement for fluorescent tags to be inserted on the molecules being photographed in many cases.

Scheuring and his lab were early adopters of the tag-free HS-AFM approach for studying molecular dynamics. The technology, which can photograph molecules in a liquid solution similar to a genuine cellular environment, employs an extremely sensitive probe, similar to a record player’s stylus, to feel its way over a molecule and therefore build up a picture of its structure. Standard HS-AFM isn’t quick enough to capture the high-speed dynamics of many proteins, but Scheuring and colleagues have developed a modified version, HS-AFM height spectroscopy (HS-AFM-HS), that works much faster by collecting dynamic changes in only one dimension: height.

The researchers used HS-AFM-HS to record the opening and closing of a relatively simple channel protein, OmpG, found in bacteria and widely studied as a model channel protein in the new study, led by the first author Raghavendar Reddy Sanganna Gari, a postdoctoral research associate in Scheuring’s laboratory. They were able to monitor OmpG gating at an effective rate of roughly 20,000 data points per second, seeing how it transitioned from open to closed states or vice versa as the acidity of the surrounding fluid varied.

More significantly, they were able to correlate structural dynamics with functional dynamics in a membrane protein of this size for the first time in a partnership with Crina Nimigean, professor of physiology and biophysics in anesthesiology, and her group at WCM.

The demonstration opens the door for a wider application of this method in basic biology and drug development.

Sanganna Gari stated,

We’re now in an exciting period of HS-AFM technology, for example using this technique to study how some drugs modulate the structural dynamics of the channel proteins they target.

Main Source

Technique reveals proteins moving as they work. By Jim Schnabel in Cornell Chronicle, August 16, 2021.

https://news.cornell.edu/stories/2021/08/technique-reveals-proteins-moving-they-work

Other Related Articles published in this Open Access Online Scientific Journal include the following:

Cryo-EM disclosed how the D614G mutation changes SARS-CoV-2 spike protein structure.

Reporter: Dr. Premalata Pati, Ph.D., Postdoc

https://pharmaceuticalintelligence.com/2021/04/10/cryo-em-disclosed-how-the-d614g-mutation-changes-sars-cov-2-spike-protein-structure/

Proteins, Imaging and Therapeutics

Larry H Bernstein, MD, FCAP, Curator, LPBI

https://pharmaceuticalintelligence.com/2015/10/01/proteins-imaging-and-therapeutics/

From High-Throughput Assay to Systems Biology: New Tools for Drug Discovery

Curator: Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2021/07/19/from-high-throughput-assay-to-systems-biology-new-tools-for-drug-discovery/

Imaging break-through: Fusion of microscopy and mass spectrometry produces detailed map of protein distribution

Reporter: Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2015/03/18/imaging-break-through-fusion-of-microscopy-and-mass-spectrometry-produces-detailed-map-of-protein-distribution/

Advanced Microscopic Imaging

Larry H Bernstein, MD, FCAP, Curator, LPBI

https://pharmaceuticalintelligence.com/2016/02/07/advanced-microscopic-imaging/

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Aortic Aneurysm Pathogenesis: The Role of TGFβRIIb Mutations in Altering Transforming Growth Factor β2 Signal Transduction

Posted in Atherogenic Processes & Pathology, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Coagulation Therapy and Internal Bleeding, Frontiers in Cardiology and Cardiovascular Disorders, Molecular Genetics & Pharmaceutical, Origins of Cardiovascular Disease, Thoracic Aorta, tagged Signal transduction, Thoracic aortic aneurysm, Transforming growth factor beta, Weill Cornell Medical College on December 30, 2013| Leave a Comment »

Aortic Aneurysm Pathogenesis: The Role of TGFβRIIb Mutations in Altering Transforming Growth Factor β2 Signal Transduction

Reporter: Aviva Lev-Ari, PhD, RN

TGFβRIIb Mutations Trigger Aortic Aneurysm Pathogenesis by Altering Transforming Growth Factor β2 Signal Transduction

Katharine J. Bee, PhD, David C. Wilkes, PhD, Richard B. Devereux, MD, Craig T. Basson, MD, PhD and Cathy J. Hatcher, PhD

Author Affiliations

From the Center for Molecular Cardiology, Greenberg Division of Cardiology, Weill Cornell Medical College, New York, NY.

Correspondence to Cathy J. Hatcher, PhD, Greenberg Division of Cardiology, Weill Cornell Medical College, 525 E. 68th St, New York, NY 10065. E-mailcjhatche@med.cornell.edu

Abstract

Background—Thoracic aortic aneurysm (TAA) is a common progressive disorder involving gradual dilation of the ascending and/or descending thoracic aorta that eventually leads to dissection or rupture. Nonsydromic TAA can occur as a genetically triggered, familial disorder that is usually transmitted in a monogenic autosomal dominant fashion and is known as familial TAA. Genetic analyses of families affected with TAA have identified several chromosomal loci, and further mapping of familial TAA genes has highlighted disease-causing mutations in at least 4 genes: myosin heavy chain 11 (MYH11), α-smooth muscle actin (ACTA2), and transforming growth factor β receptors I and II (TGFβRI and TGFβRII).

Methods and Results—We evaluated 100 probands to determine the mutation frequency in MYH11, ACTA2, TGFβRI, and TGFβRII in an unbiased population of individuals with genetically mediated TAA. In this study, 9% of patients had a mutation in one of the genes analyzed, 3% of patients had mutations in ACTA2, 3% in MYH11, 1% in TGFβRII, and no mutations were found in TGFβRI. Additionally, we identified mutations in a 75 base pair alternatively spliced TGFβRII exon, exon 1a that produces the TGFβRIIb isoform and accounted for 2% of patients with mutations. Our in vitro analyses indicate that the TGFβRIIb activating mutations alter receptor function on TGFβ2 signaling.

Conclusions—We propose that TGFβRIIb expression is a regulatory mechanism for TGFβ2 signal transduction. Dysregulation of the TGFβ2 signaling pathway, as a consequence of TGFβRIIb mutations, results in aortic aneurysm pathogenesis.

SOURCE:

Circulation: Cardiovascular Genetics.2012; 5: 621-629

Published online before print October 24, 2012,doi: 10.1161/ CIRCGENETICS.112.964064

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“R145C” variant of the ApoE gene is found in People of African Descent, linked to Increased Levels of Triglycerides, Obesity, Diabetes, Stroke and Cardiovascular Diseases

Posted in Atherogenic Processes & Pathology, Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, HTN, Myocardial metabolism, Myocardial ischemia, myocardial perfusion, Myocardial adenine nucleotide metabolism, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, tagged African American, African diaspora, Apolipoprotein E, Black people, Weill Cornell Medical College on December 2, 2013| Leave a Comment »

“R145C” variant of the ApoE gene is found in People of African Descent, linked to Increased Levels of Triglycerides, Obesity, Diabetes, Stroke and Cardiovascular Diseases

Reporter: Aviva Lev-Ari, PhD, RN

Gene Mutation May Explain Heart Disease Risk Among African-Americans

December 2, 2013

MONDAY, Dec. 2, 2013 (HealthDay News) — A genetic mutation associated with an increased risk of heart disease, type 2 diabetes and other health problems is common in Africans and people of African descent worldwide, according to a new study.

The findings may help explain why Africans and people of African descent are more likely to develop heart disease and diabetes than many other racial groups, the Weill Cornell Medical College researchers said.

The mutation in the ApoE gene is linked to increased levels of triglycerides, which are fats in the blood associated with conditions such as obesity, diabetes, stroke and heart disease.

The researchers’ analysis of worldwide data revealed that the “R145C” variant of the ApoE gene is found in 5 percent to 12 percent of Africans and people of African descent, especially those from sub-Saharan Africa. The variant is rare in people who are not African or of African descent.

“Based on our findings, we estimate that there could be 1.7 million African-Americans in the United States and 36 million sub-Saharan Africans worldwide with the variant,” study senior author Dr. Ronald Crystal, chairman of genetic medicine at Weill Cornell, said in a college news release.

On average, African-Americans with the mutation had 52 percent higher triglyceride levels than those without the variant, according to the study, which was published online Nov. 18 in the American Journal of Cardiology.

“The prevalence of the ApoE mutation may put large numbers of Africans and African descendants worldwide at risk for a triglyceride-linked disorder,” Crystal said. “But we don’t yet know the extent of that risk or its health consequences.”

“Inheriting this genetic variant does not mean a person is going to get heart disease and other diseases,” he said. “It increases their risk, and screening for fats in the blood — both cholesterol and triglycerides — as well as maintaining a healthy lifestyle is important.”

“There are many factors at work in these diseases,” Crystal said. “This may be one player.”

More information

The American Heart Association has more about black Americans and heart disease and stroke.

SOURCE

http://news.health.com/2013/12/02/gene-mutation-may-explain-heart-disease-risk-among-african-americans/

Dalio Institute of Cardiovascular Imaging @ NewYork-Presbyterian Hospital and Weill Cornell Medical College

Posted in Medical Imaging Technology, Image Processing/Computing, MRI, CT, Nuclear Medicine, Ultra Sound, tagged Cedars-Sinai Medical Center, Cornell University, NewYork-Presbyterian, NewYork-Presbyterian Hospital, NewYork-Presbyterian Hospital and Weill Cornell Medicine, Ray Dalio, Weill Cornell, Weill Cornell Medical College on November 12, 2013| Leave a Comment »

Detecting and Treating Silent Heart Disease: NewYork-Presbyterian Hospital and Weill Cornell Medical College Launch New Institute

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED on 7/15/2018

The Dalio Institute

The Dalio Institute for Cardiovascular Imaging at NewYork-Presbyterian Hospital combines research, clinical care and education to uncover new answers about preventing heart disease. A joint NewYork-Presbyterian Hospital and Weill Cornell Medicine venture, the institute employs a multidisciplinary, multimodality approach to the detection and treatment of heart disease. Directed by Dr. James K. Min, the institute’s mission is to innovate, integrate and educate, goals that will be achieved through cutting-edge research, transformations of current clinical paradigms and dissemination of knowledge.

Rooted in the central role of imaging techniques to better diagnose cardiovascular disease, the institute not only uses state-of-the-art tools such as MRI, CT and PET scanners, but also focuses on the development of novel next-generation technologies and diagnostic tests. Applying a team-based approach that draws on the expertise of physicians and scientists in radiology, cardiology, genetics, proteomics, and computational biology, the institute’s primary research initiative is to identify the specific coronary artery lesion that is responsible for heart attacks or sudden cardiac deaths.

The Dalio Institute uses imaging technologies in conjunction with other cutting-edge diagnostic tests, including blood markers of inflammation, protein expression and metabolism. The clinical program serves patients in the outpatient and inpatient setting, as well as in the emergency department. Three specific initiatives within the clinical program emphasize early identification of heart disease in women, ethnic minorities and young patients with a family history of premature heart disease.

https://hearthealth.weillcornell.org/about-us/dalio-institute

Based on your medical history, we can use calculators to estimate your risk of having a cardiovascular event over time. Risk calculators use various factors including age, sex, and race, in addition to “traditional” cardiac risk factors such as smoking, diabetes, high cholesterol and high blood pressure. Our practice uses several common risk calculators. It is important to emphasize that risk calculators may be imperfect, especially in patients with unique risk factors. These might include a family history of early heart disease or a chronic inflammatory disorder. Therefore, it may be beneficial to consider a full cardiovascular assessment to explore your personal risk and strategies to reduce it.

Risk calculators may be of interest to you, but we caution that the results should be interpreted and reviewed by a trained clinical provider.

Heart Age Predictor Using BMI (Body Mass Index) Source: Framingham Heart Study

ASCVD Risk Estimator Source: American College of Cardiology/American Heart Association
Risk Score Calculator Source: The Multi-Ethnic Study of Atherosclerosis (MESA)
Coronary Artery Calcium Score Reference Values Source: The Multi-Ethnic Study of Atherosclerosis (MESA)
Arterial Age Calculator Source: The Multi-Ethnic Study of Atherosclerosis (MESA)

https://hearthealth.weillcornell.org/risk-assessments

Diagnostic Tests

Your cardiovascular risk assessment at HeartHealth always begins with a detailed medical history and physical exam. The physical exam is often not able to fully diagnose problems, nor is it ever able to diagnose coronary artery disease or calcification. We therefore offer the most up-to-date noninvasive imaging studies to visualize the heart muscle, valves, blood flow and coronary arteries. We have state-of-the-art equipment and world-renowned experts to interpret these studies.

All of the following will be offered at HeartHealth (Click on the test name to view more information):

Cardiac Computed Tomography Angiography (CTA)

Cardiac Magnetic Resonance Imaging (MRI)

Cardiac PET/CT

Echocardiogram/Doppler Transthoracic

Exercise Electrocardiogram or ETT (Exercise Treadmill Test)

Exercise Stress Echocardiogram & Dobutamine Stress Echocardiogram

Myocardial Perfusion Scan (aka Nuclear Stress Test)

November 12, 2013

Funded by a $20 million gift from the Dalio Foundation, the institute will combine research, clinical care, and education to uncover new answers about preventing heart disease

NEW YORK – To help reduce the burden of cardiovascular disease, the nation’s leading killer, NewYork-Presbyterian Hospital and Weill Cornell Medical College have created the Dalio Institute of Cardiovascular Imaging. Raymond T. Dalio, a life trustee of NewYork-Presbyterian Hospital, has made a gift of $20 million through his Dalio Foundation in support of the institute.

The Dalio Institute of Cardiovascular Imaging will employ a multidisciplinary, multimodality approach to the detection and treatment of heart disease, with a focus on finding new answers about prevention of heart disease in at-risk individuals and ultimately save lives. Its mission is to innovate, integrate, and educate, goals that will be achieved through cutting-edge research, transformations of current clinical paradigms, and dissemination of knowledge. Dr. James K. Min, an expert in cardiovascular imaging and a physician-scientist who has led several large-scale multicenter clinical trials, has been appointed director of the Dalio Institute of Cardiovascular Imaging. Dr. Min is an attending physician at NewYork-Presbyterian Hospital and a full-time faculty member in the Department of Radiology at Weill Cornell Medical College. He joins NewYork-Presbyterian/Weill Cornell from the Cedars-Sinai Medical Center, where he was director of cardiac imaging research and co-director of cardiac imaging. Rooted in the central role of imaging techniques to better diagnose cardiovascular disease, the institute will not only use state-of-the-art tools such as MRI, CT, and PET scanners, but will also focus on the development of novel next-generation technologies and diagnostic tests. Applying a team-based approach that draws on the expertise of physicians and scientists in radiology, cardiology, genetics, proteomics, and computational biology, the institute’s primary research initiative is to identify the “vulnerable plaque,” or the specific coronary artery lesion that is responsible for a future heart attack or sudden cardiac death.“The vulnerable plaque is the holy grail in the diagnostic work-up of individuals with suspected coronary artery disease, and its elusive nature has precluded the timely treatment of millions of high-risk individuals,” says Dr. Min. “We will apply an array of innovative hardware and software imaging technologies to improve identification of the vulnerable plaque, and then seek to apply these findings in large-scale multicenter clinical trials and registries to encourage full integration of our research findings into clinical practice.”

To develop the world-class clinical program to diagnose early cardiovascular disease, the Dalio Institute of Cardiovascular Imaging will use state-of-the-art imaging technologies in conjunction with other cutting-edge diagnostic tests, including blood markers of inflammation, protein expression, and metabolism. The clinical program will serve patients in the outpatient and inpatient setting, as well as in the emergency department. Three specific initiatives within the clinical program will emphasize

early identification of heart disease in women,
ethnic minorities, and
young patients with a family history of premature heart disease.

The institute’s educational mission will focus on disseminating knowledge of the latest advances in cardiovascular imaging through the education of physicians, physician trainees, and allied health professionals through formal didactic curricula and symposia.

“More than half of people who die from sudden heart attacks never knew they were at risk because their underlying heart conditions had never been diagnosed,” says Dr. Min. “Many heart attacks can be prevented if people know of the extent and severity of their asymptomatic heart disease and are properly treated. By bringing together a multidisciplinary group of experts, the Dalio Institute of Cardiovascular Imaging will not just offer the latest imaging techniques for early detection, but will also develop disruptive technologies to fight the battle against heart disease. Ultimately, these pioneering methods aim to challenge current clinical paradigms in order to reduce the morbidity and mortality associated with cardiovascular disease.”

“Establishing the Dalio Institute of Cardiovascular Imaging is an incredibly significant milestone in our fight against heart disease,” says Dr. Steven J. Corwin, CEO of NewYork-Presbyterian Hospital and a cardiologist by training. “While modern medicine offers highly sophisticated tools for treating heart disease, we still have a long way to go in terms of identifying high-risk individuals with early-stage disease so that we can prevent catastrophic outcomes and save lives. Dr. Min’s unique background, expertise, and clinical research experience make him ideally suited to lead the institute and its groundbreaking initiatives. We are thrilled that Dr. Min has joined us, and we are extraordinarily grateful to Ray Dalio for his vision and generous support.”

“The interdisciplinary nature of the new Dalio Institute of Cardiovascular Imaging exemplifies the best in translational research – investigations that can make lifesaving impact on our patients,” says Dr. Laurie H. Glimcher, the Stephen and Suzanne Weiss Dean of Weill Cornell Medical College. “Dr. Min has a proven track record of effectively testing novel theories, and we enthusiastically support what we know will be innovative research at the institute.”

NewYork-Presbyterian/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances – including the development of the Pap test for cervical cancer; the synthesis of penicillin; the first successful embryo-biopsy pregnancy and birth in the U.S.; the first clinical trial for gene therapy for Parkinson’s disease; the first indication of bone marrow’s critical role in tumor growth; and, most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. NewYork-Presbyterian Hospital also comprises NewYork-Presbyterian/Columbia University Medical Center, NewYork-Presbyterian/Morgan Stanley Children’s Hospital, NewYork-Presbyterian/Westchester Division, NewYork-Presbyterian/The Allen Hospital, and NewYork-Presbyterian/Lower Manhattan Hospital. NewYork-Presbyterian is the #1 hospital in the New York metropolitan area and is consistently ranked among the best academic medical institutions in the nation, according to U.S.News & World Report. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit http://www.nyp.org and weill.cornell.edu.

SOURCE

http://www.dotmed.com/news/story/22416?p_begin=0

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Precision Medicine: The Future of Medicine?

Posted in Personalized and Precision Medicine & Genomic Research, tagged CBS This Morning, Koch Institute Professor, Massachusetts Institute of Technology, MIT, Robert Langer, Weill Cornell Medical College, Weill Cornell Medical College of Cornell University on July 1, 2013| 1 Comment »

Precision Medicine: The Future of Medicine?

Reporter: Aviva Lev-Ari, PhD, RN

Dr. Laurie Glimcher, dean of Weill Cornell Medical College, and Dr. Robert Langer, the Koch Institute Professor at MIT, talk to the “CBS This Morning” co-hosts about what’s next in the fight against diseases like Alzheimer’s, cancer, and diabetes.

VIEW VIDEO

http://www.cbsnews.com/video/watch/?id=50149783n

Free Webinar:

The Economics of Precision Medicine:

How Personalizing Treatment can Bend the Cost Curve by

Improving the Value Delivered by Healthcare Innovations

In a world where it is clear that healthcare costs must be contained, how can we afford to pay for innovation? This webinar will explore how personalizing treatment can offer an escape from the innovation-cost conundrum. By simultaneously increasing clinical development efficiency and the treatment effectiveness, targeting clinical innovations to the patients most likely to benefit can improve healthcare value per dollar spent while maintaining the ROI levels needed to support investment in innovation. We believe precision medicine should play a more prominent role in the cost containment discussion of healthcare reform.

By attending this Webinar, you will learn how to:

Help clients develop product development and commercialization strategies that get leverage from the benefits of precision medicine

Support positioning of innovations as part of the healthcare solution, not the problem

Understand and communicate the value proposition of precision medicine for payers, government decision makers, and legislators

The Economics of Precision Medicine: How Personalizing Treatment can Bend the Cost Curve by Improving the Value Delivered by Healthcare Innovations

Thursday, July 25, 2013

11:30 am PDT / 2:30 pm EDT

1 hour

Who should attend:

Franchise and Marketing Leaders

Therapeutic Area Leads

Medical Affairs

Government Affairs/Public Policy

Health Economics and Market Access

Webinar agenda:

Is the high cost of healthcare innovation incompatible with control of healthcare costs?

Cost-effectiveness criteria and how they can be met

Taking cost out of clinical development

Case Example: How everyone can win

Practical impact on development and commercialization strategies

Q&A

Speaker information:

David Parker, Ph.D., Vice President, Market Access Strategy, Precision for Medicine

Vicki L. Seyfert-Margolis, Chief Scientific and Strategy Officer, Precision for Medicine

Harry Glorikian, Managing Director, Strategy, Precision for Medicine

Cambridge Healthtech Institute, 250 First Avenue, Suite 300, Needham, MA 02494

Tel: 781-972-5400 | Fax: 781-972-5425

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Genomic Liberty of Ownership, Genome Medicine and Patenting the Human Genome

Posted in Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Genome Biology, Genomic Testing: Methodology for Diagnosis, Health Economics and Outcomes Research, Health Law & Patient Safety, Medical and Population Genetics, Personalized and Precision Medicine & Genomic Research, Pharmacogenomics, Population Health Management, Genetics & Pharmaceutical, Regulated Clinical Trials: Design, Methods, Components and IRB related issues, tagged DNA, genetics, human genome, Nucleic acid sequence, Patent, Supreme Court, Weill Cornell Medical College on March 27, 2013| 5 Comments »

Curator: Aviva Lev-Ari, PhD, RN

In their discussion, the researchers argue that the U.S. Supreme Court now has a chance to shape the balance between the medical good versus inventor protection, adding that, in their opinion, the court should limit the patenting of existing nucleotide sequences, due to their broad scope and non-specificity in the human genome.

“I am extremely pro-patent, but I simply believe that people should not be able to patent a product of nature,” Dr. Mason says. “Moreover, I believe that individuals have an innate right to their own genome, or to allow their doctor to look at that genome, just like the lungs or kidneys. Failure to resolve these ambiguities perpetuates a direct threat to genomic liberty, or the right to one’s own DNA.”

http://www.sciencedaily.com/releases/2013/03/130326101614.htm

Supreme Court May Decide Whether We Own Our Genes

March 26, 2013

Image Credit: Photos.com

Brett Smith for redOrbit.com – Your Universe Online

They may be responsible for everything in your life, from conception to death, they may be inside every living cell in your body – but you do not own your own genes, legally speaking.

According to a report in Genome Medicine, patents essentially cover the entire human genome, hampering research and raising the question of “genomic liberty.”

The legal standing of genomic patents could change next month when the Supreme Court reviews patent rights for two key breast and ovarian cancer genes, BRCA1 and BRCA2, which include segments of genetic code as small as 15 nucleotides, known as 15mers.

“This is, so to speak, patently ridiculous,” said report co-author Dr. Christopher E. Mason of Weill Cornell Medical College. “If patent claims that use these small DNA sequences are upheld, it could potentially create a situation where a piece of every gene in the human genome is patented by a phalanx of competing patents.”

In their report, Mason and Dr. Jeffrey Rosenfeld, an assistant professor of medicine at the University of Medicine & Dentistry of New Jersey, looked at patents for two different categories of DNA fragments:

long and
short.

They revealed 41 percent of the human genome is covered by “long” DNA patents that can include whole genes. Because many genes share similar sequences within their code that are patented, the combination of all these “short” DNA patents covers 100 percent of the genome.

“This demonstrates that short patent sequences are extremely non-specific and that a 15mer claim from one gene will always cross-match and patent a portion of another gene as well,” Mason said. “This means it is actually impossible to have a 15mer patent for just one gene.”

To reach their conclusions, the researchers first looked at small sequences within BRCA1 and noticed one of the company’s BRCA1 patents also covered almost 690 other human genes. Some of these genes are unrelated to breast cancer – instead being associated with brain development and heart functioning.

Next, researchers determined how many known genes are covered by 15mers in current patent claims. They found 58 patents covered at least ten percent of all bases of all human genes. The broadest patent claim matched 91.5 percent of human genes. When the team took patented 15mers and matched them to known genes, they found 100 percent of known genes are patented.

Finally, the team also looked at “long” DNA sequences from existing gene patents, ranging from a few dozen to thousands of base pairs. They found these long sequences added up to 41 percent of known human genes.

“There is a real controversy regarding gene ownership due to the overlap of many competing patent claims. It is unclear who really owns the rights to any gene,” Rosenfeld said. “While the Supreme Court is hearing one case concerning just the BRCA1 patent, there are also many other patents whose claims would cover those same genes.

“Do we need to go through every gene to look at who made the first claim to that gene, even if only one small part? If we resort to this rule, then the first patents to be granted for any DNA will have a vast claim over portions of the human genome,” he added.

Another legal question surrounds patented DNA sequences that cross species boundaries. The researchers found one company has the rights to 84 percent of all human genes for a patent they received for cow breeding.

Source: Brett Smith for redOrbit.com – Your Universe Online

Topics: Health Medical Pharma, Genetics, Gene patent, Biology, Gene, Living modified organism, Association for Molecular Pathology v. U.S. Patent and Trademark Office, BRCA1, DNA, Supreme Court, Human genome

SOURCE:

http://www.redorbit.com/news/health/1112811074/supreme-court-gene-patents-long-short-dna-032613/

Human Genome: Name Your Price

Posted March 27, 2013 – 12:51 by a staff writer

Weill Cornell Medical College researchers have issued a warning that, according to the patent system, the vast majority of humans on the planet don’t ‘own’ their own genes, and in fact their biological make-up is being exploited for profit. Even seemingly innocent research into cow breeding can cover human genetic make-up.

As spotted by a Slashdot user, two researchers combing through patents on human DNA discovered that over 40,000 patents on DNA molecules have effectively declared the human genome for profit. A report in medical journal Genome Medicine said that humans may be losing their grip on “individual genomic liberty”.

Looking at two kinds of patented DNA sequences, or long and short fragments, 41 percent of the human genome is covered by DNA patents that can cover entire genes. According to the research, if all of the short sequence patents were allowed in aggregate they could cover 100 percent of the human genome.

Lead author Dr Christopher E Mason and co-author Dr Jeffrey Rosenfeld warned that short sequences from patents cover “virtually the entire genome, even outside of genes”. A Weill Cornell assistant professor asked: “How is it possible that my doctor cannot look at my DNA without being concerned about patent infringement?”

There will be a Supreme Court hearing about genomic patent rights next month that will debate the morality of a molecular diagnostic company claiming patents on key cancer genes, as well as on any small sequence of code within the BRCA1 gene. Cornell explained that at present, genes are able to be patented by researchers working in companies and institutions who discover genes that have potentially useful applications, like in testing for cancer risks. Because the patents can be held by companies or organisations, it is possible for the patent owner to charge doctors thousands of dollars for each diagnostic test.

The authors pointed out that in their studies, while engaged in research, it is common to come across a gene that’s patented “almost every day”. Their paper promises to examine how genes may have been impacted by held patents, and the extent of intellectual property on the genome. Gene patents can also relate between different species – for example, a company may have a patent for breeding cows that also covers a large percentage of human genes. They cited one company that owns 84 percent of all human genes because of a patent for cow breeding.

“There is a real controversy regarding gene ownership due to the overlap of many competing patent claims. It is unclear who really owns the rights to any gene,” Dr Rosenfeld said. “Do we need to go through every gene to look at who made the first claim to that gene, even if only one small part? If we resort to this rule, then the first patents to be granted for any DNA will have a vast claim over portions of the human genome.”

Lead author Dr Mason insisted he is pro-patent, but believes people “should not be able to patent a product of nature”.

“I believe that individals have an innate right to their own genome,” he said.

http://www.tgdaily.com/hardware-brief/70513-human-genome-name-your-price#BUKfEtjWKb3gq7X3.99

http://www.tgdaily.com/hardware-brief/70513-human-genome-name-your-price#!/exjun_

Volume One: Genomics Orientations for Individualized Medicine

Chapter 20: Genomics & Ethics

20.1 Genomics & Ethics: DNA Fragments are Products of Nature or Patentable Genes?

Aviva Lev-Ari, PhD, RN

20.2 Understanding the Role of Personalized Medicine

Larry H Bernstein, MD, FACP

20.3 Attitudes of Patients about Personalized Medicine

Larry H Bernstein, MD, FACP

20.4 Genome Sequencing of the Healthy

Larry H. Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN

20.5 Genomics in Medicine – Tomorrow’s Promise

Larry H. Bernstein, MD, FACP

20.6 The Promise of Personalized Medicine

Larry H. Bernstein, MD, FACP

20.7 Ethical Concerns in Personalized Medicine: BRCA1/2 Testing in Minors and Communication of Breast Cancer Risk

Stephen J. Williams, Ph.D

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Gates Foundation funds research to improve health in developing countries

Posted in Population Health Management, Genetics & Pharmaceutical, Population Health Management, Nutrition and Phytochemistry, tagged Bill & Melinda Gates Foundation, Bill Steele, Gates Foundation, Keith Perry, Weill Cornell Medical College, Weill Cornell Medical College of Cornell University, World Health Organization on November 16, 2012| 1 Comment »

Reporter: Aviva Lev-Ari, PhD, RN

Gates Foundation funds research to improve health in developing countries

Division of Nutritional Sciences

As a volunteer in the summer of 2008, Lauren Braun ’11 fills a prescription in a makeshift rural pharmacy in Peru.

Provided/Alma Sana

Alma Sana bracelets use symbols to avoid language barriers.

By Bill Steele
and Krishna Ramanujan

A Cornell plant virologist, an alumna and three Weill Cornell Medical College researchers have each received grants from the Bill & Melinda Gates Foundation‘s Grand Challenges in Global Health initiative.

One grant awarded to Jeremy Thompson in the Department of Plant Pathology and Plant-Microbe Biology will fund a project that takes advantage of new technology to rapidly determine the structure of RNA in viruses, which may lead to a new method for developing virus-resistant plants. Thompson, a research associate in the lab of Keith Perry, associate professor of plant pathology, will work with Perry to uncover new targets for plant virus resistance and with Julius Lucks, assistant professor of chemical and biomolecular engineering, who has developed new RNA structure mapping technology.

Viruses are known to use their RNA to hijack the replication machinery in host cells to make more copies of the virus. The researchers hope that determining the RNA structure will reveal plant proteins that are involved in viral replication.

“We want to try and map the structure of viral RNA, map the way it folds, and then we can potentially identify host proteins that are involved in virus replication and function,” said Thompson.

Once these plant proteins are identified, the researchers will look for genes that code for those proteins and try to alter their expression within the plant. “If we can affect the amount of protein involved, we can potentially hinder virus replication,” Thompson added. Using refined engineering methods to knock out or silence such protein-coding genes, the researchers may then create lines of virus-resistant plants.

The researchers will begin by examining viruses and host proteins in bean, tobacco and arabidopsis; bean, because of its importance as a staple in developing countries and the latter two because their genomes have been fully sequenced.

The one-and-a-half year, $100,000 grant represents a first phase that, if successful, allows the team to become eligible for phase two and an additional $1 million.

Braun

As the main objective of the Gates Foundation Grand Challenges in Global Health initiative is to improve the quality of life in developing countries, this project aims to “improve resistance against particular diseases for small-holder farmers, with all intellectual property being open to developing countries,” Thompson said. Plant viruses lead to billions of dollars in agricultural production losses each year.

Lauren Braun ’11 received a $100,000 grant to field-test in Peru a simple, inexpensive immunization-tracking bracelet for babies. Braun conceived the idea after spending the summer of 2008 as a volunteer at two rural health clinics in Peru, and she presented it on campus in the Entrepreneurship@Cornell’s 2011 Big Idea Competition.

The World Health Organization estimates that globally 1.5 million children die of vaccine-preventable diseases each year, and one in five children will die from such a disease before age 5.

Braun formed the nonprofit Alma Sana Inc. (Spanish for healthy soul) to manufacture and distribute the bracelets, which bypass language barriers and illiteracy by using symbols to show mothers the vaccinations their children need and numbers to show when they are due. The bracelet is to be worn by a child from birth to age 4, with the goal that more children will live to age 5.

A paper reminder system failed, Braun reports, because children are not brought in for their vaccinations and stored vaccine spoils and must be discarded, increasing costs. The bracelet also tells public health workers which vaccination each child needs.

The Gates Foundation initiative seeks new approaches to optimize immunization systems. In 2010, they said, a quarter of a million doses of pentavalent vaccine, costing nearly $1 million, expired in one country’s central store because the system charged with delivering them was not ready to manage it.

Three researchers at Weill Cornell Medical College have received Gates Foundation grants totaling $1.5 million from the Grand Challenges initiative for innovative research aimed at fighting HIV and tuberculosis.

SOURCE:

http://www.news.cornell.edu/stories/Nov12/GlobalHealthGrants.html

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Repair damaged blood vessels in heart disease, stroke, diabetes and trauma: Cellular Reprogramming amniotic fluid-derived cells into Endothelial Cells

Posted in Bio Instrumentation in Experimental Life Sciences Research, Biological Networks, Gene Regulation and Evolution, Biomarkers & Medical Diagnostics, Cardiovascular Pharmacogenomics, Cell Biology, Signaling & Cell Circuits, Chemical Genetics, Frontiers in Cardiology and Cardiovascular Disorders, Genome Biology, Genomic Testing: Methodology for Diagnosis, Molecular Genetics & Pharmaceutical, Origins of Cardiovascular Disease, Personalized and Precision Medicine & Genomic Research, Stem Cells for Regenerative Medicine, Technology Transfer: Biotech and Pharmaceutical, tagged Goldilocks Principle, Howard Hughes Medical Institute, Rafii, Stem cell, Weill Cornell, Weill Cornell Medical College, Weill Cornell Medical College of Cornell University on October 18, 2012| 3 Comments »

Reporter: Aviva Lev-Ari, PhD, RN

Public release date: 18-Oct-2012
Contact: Lauren Woods
law2014@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College

New study shows reprogrammed amniotic fluid cells could treat vascular diseases

Weill Cornell Researchers discover a new effective approach for converting amniotic fluid-derived cells into endothelial cells to repair damaged blood vessels in heart disease, stroke, diabetes and trauma

NEW YORK (Oct. 18, 2012) — A research team at Weill Cornell Medical College has discovered a way to utilize diagnostic prenatal amniocentesis cells, reprogramming them into abundant and stable endothelial cells capable of regenerating damaged blood vessels and repairing injured organs.

Their study, published online today in Cell, paints a picture of a future therapy where amniotic fluid collected from thousands of amniocentesis procedures yearly, during mid-pregnancy to examine fetal chromosomes, would be collected with the permission of women undergoing the test. These cells, which are not embryonic, would then be treated with a trio of genes that reprogram them quickly into billions of endothelial cells — the cells that line the entire circulatory system. The new endothelial cells could be frozen and banked the same way blood is, and patients in need of blood vessel repair would be able to receive the cells through a simple injection.

If proven in future studies, this novel therapy could dramatically improve treatment for disorders linked to a damaged vascular system, including heart disease, stroke, lung diseases such as emphysema, diabetes, and trauma, says the study’s senior investigator, Dr. Shahin Rafii, the Arthur B. Belfer Professor in Genetic Medicine at Weill Cornell Medical College and co-director of its Ansary Stem Cell Institute.

“Currently, there is no curative treatment available for patients with vascular diseases, and the common denominator to all these disorders is dysfunction of blood vessels, specifically endothelial cells that are the building blocks of the vessels,” says Dr. Rafii, who is also a Howard Hughes Medical Institute investigator.

But these cells do much more than just provide the plumbing to move blood. Dr. Rafii has recently led a series of transformative studies that show endothelial cells in blood vessels produce growth factors that actively participate in organ maintenance, repair and regeneration. So while damaged vessels cannot repair the organs they nurture with blood, he says an infusion of new endothelial cells could.

“Replacement of the dysfunctional endothelial cells with transplantation of normal, properly engineered cultured endothelial cells could potentially provide for a novel therapy for many patients,” says study co-author Dr. Sina Rabbany, adjunct associate professor of bioengineering in genetic medicine at Weill Cornell. “In order to engineer tissues with clinically relevant dimensions, endothelial cells can be assembled into porous three-dimensional scaffolds that, once introduced into a patient’s injured organ, could form true blood vessels.”

Dr. Rafii says that this study will potentially create a new field of translational vascular medicine. He estimates that as few as four years are needed for the preclinical work to seek FDA approval to start human clinical trials to advance the potential of reprogrammed endothelial cells for treatment of vascular disorders.

As part of their study, the research team proved, in mice, that endothelial cells reprogrammed from human amniotic cells could engraft into an injured liver to form stable, normal and functional blood vessels. “We have shown that these engrafted endothelial cells have the capacity to produce unique growth factors to promote regeneration of the liver cells,” says the study’s lead investigator, Dr. Michael Ginsberg, a senior postdoctoral associate in Dr. Rafii’s laboratory.

“The novelty of this technique is that, from 100,000 amniotic cells — a small amount — we grew more than six billion new authentic endothelial cells within a matter of weeks,” Dr. Ginsberg says. “And when we injected these cells into mice, a substantial amount of them engrafted into regenerating vessels. It was remarkable to see that these cells went right to work building new blood vessels in the liver as well as producing the right growth factors that could potentially regenerate and repair injured organs.”

The Goldilocks of Cellular Reprogramming

To date, there have been many failed attempts to clinically produce endothelial cells that can be used to treat patients. Isolation of endothelial cells from adult organs so they can be grown in the laboratory is not efficient, according to Dr. Daylon James, study co-author and an assistant professor of stem cell biology in reproductive medicine at Weill Cornell Medical College. Attempts to produce the cells from the body’s master pluripotent stem cells have also not worked out. Experiments have shown that prototypical pluripotent stem cells, such as embryonic stem cells, which have the potential to become any cell in the body, produce endothelial cells but often grow poorly, and if not fully differentiated could potentially cause cancer. “Coaxing adult cells to revert to a stem-like state so they can then be pushed to form endothelial cells is, at this point, not clinically feasible, and ongoing studies in my lab are focused on achieving this goal,” says Dr.

James, who is also assistant professor of stem cell biology in obstetrics and gynecology and genetic medicine at Weill Cornell. Therefore, Dr. Rafii’s team searched for a new source of cells that they could turn into a vast supply of stable endothelial cells. They probed human amniotic fluid-derived cells, which some studies had suggested have the potential to become differentiated cell types, if stimulated in the right way — which no one had yet identified.

In their first experiments with these cells three years ago, Dr. Ginsberg used cells taken from an amniocentesis given at 16 weeks of gestation. Researchers found that amniotic cells are the “Goldilocks” of cellular programming. “They are not as plastic and unstable as endothelial cells derived from embryonic cells or as stubborn as those produced from reprogramming differentiated adult cells,” Dr. Ginsberg says. Instead, he says amniotic cells provide conditions that are just right — the so-called “Goldilocks Principle” — for producing endothelial cells.

But in order to make that discovery, the researchers had to know how to reprogram the amniotic cells. To this end, they looked for the genes that embryonic stem cells use to differentiate into endothelial cells. Dr. Rafii’s group identified three genes that are expressed during vascular development, all of which are members of the E-twenty six (ETS) family of transcription factors known to regulate cellular differentiation, especially blood vessel formation.

Next, they used gene transfer technology to insert the three genes into mature amniotic cells, and then shut one of them off after a brief and critical period of activity by using a special molecular inhibitor. Remarkably, 20 percent of the amniotic cells could efficiently be reprogrammed into endothelial cells. “This is quite an achievement since current strategies to reprogram adult cells result less than one percent of the time in successful reprogramming into endothelial cells,” says Dr. Rafii.

“These transcription factors do not cause cancer, and the endothelial cells reprogrammed from human amniotic cells are not tumorigenic and could in the future be infused into patients with a large margin of safety,” Dr. Ginsberg says.

The findings suggest that other transcription factors could be used to reprogram the amniotic cells into many other tissue-specific cells, such as those that make up muscles, the brain, pancreatic islet cells and other parts of the body.

“While our work focused primarily on the reprogramming of amniotic cells into endothelial cells, we surmise that through the use of other transcription factors and growth conditions, our group and others will be able to reprogram mouse and human amniotic cells virtually into every organ cell type, such as hepatocytes in the liver, cardiomyocytes in heart muscle, neurons in the brain and even chondrocytes in cartilage, just to name a few,” Dr. Ginsberg says.

“Obviously, the implications of these findings would be enormous in the field of translational regenerative medicine,” emphasizes study co-author Dr. Zev Rosenwaks, the Revlon Distinguished Professor of Reproductive Medicine in Obstetrics and Gynecology at Weill Cornell Medical College and director and physician-in-chief of the Ronald O. Perelman and Claudia Cohen Center for Reproductive Medicine at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. “The greatest obstacle to overcome in the pursuit to regenerate specific tissues and organs is the requirement for substantial levels of cells — in the billions — that are stable, safe and durable. Our approach will bring us closer to this milestone.”

“Most importantly, these endothelial cells could be reprogrammed from amniotic cells from genetically diverse individuals,” says co-author Dr. Venkat R. Pulijaal, director of the Cytogenetic Laboratory, associate professor of clinical pathology and laboratory medicine at Weill Cornell. What endothelial cells a patient receives would depend on their human leukocyte antigen (HLA) type, which is a set of self-recognition molecules that enable doctors to match a patient with potential donors of blood or tissue.

“Selecting the proper immunologically matched endothelial cells for each patient would be akin to blood typing. There are only so many varieties, which are well represented across the amniotic fluid cells that could be obtained, frozen and banked from wide variety of ethnic groups around the world,” Dr. Rafii says.

A patent has been filed on the discovery.

Other study co-authors from Weill Cornell Medical College include: Dr. Bi-Sen Ding, Dr. Daniel Nolan, Dr. Fuqiang Geng, Dr. Jason M. Butler, Dr. William Schachterle, Dr. Susan Mathew, Dr. Stephen T. Chasen, Dr. Jenny Xiang, Dr. Koji Shido and Dr. Olivier Elemento.

Dr. Rafii’s research is funded by the Howard Hughes Medical Institute, the National Heart, Lung, and Blood Institute, the Ansary Stem Cell Institute at Weill Cornell Medical College, the Empire State Stem Cell Board and New York State Department of Health grants, and the Qatar National Priorities Research Foundation.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University’s medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research from bench to bedside, aimed at unlocking mysteries of the human body in health and sickness and toward developing new treatments and prevention strategies. In its commitment to global health and education, Weill Cornell has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances — including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson’s disease, and most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. Weill Cornell Medical College is affiliated with NewYork-Presbyterian Hospital, where its faculty provides comprehensive patient care at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. The Medical College is also affiliated with the Methodist Hospital in Houston. For more information, visit weill.cornell.edu.

Source:

http://www.eurekalert.org/pub_releases/2012-10/nyph-nss101812.php