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Archive for the ‘Interviews with Scientific Leaders’ Category

Featuring Computational and Systems Biology Program at Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute (SKI), The Dana Pe’er Lab

Posted in Interviews with Scientific Leaders, Single Cell Genomics, Single-cell sequencing, Variation in human protein-coding regions on June 16, 2019| Leave a Comment »


Featuring Computational and Systems Biology Program at Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute (SKI), The Dana Pe’er Lab

 

Reporter: Aviva Lev-Ari, PhD, RN

A lecture by Dana Pe’er is included, below in the eProceedings which I generated in Real Time on 6/14/2019 @MIT

eProceeding 2019 Koch Institute Symposium – 18th Annual Cancer Research Symposium – Machine Learning and Cancer, June 14, 2019, 8:00 AM-5:00 PM ET MIT Kresge Auditorium, 48 Massachusetts Ave, Cambridge, MA

https://pharmaceuticalintelligence.com/2019/03/12/2019-koch-institute-symposium-machine-learning-and-cancer-june-14-2019-800-am-500-pmet-mit-kresge-auditorium-48-massachusetts-ave-cambridge-ma/

 

 

Memorial Sloan Kettering Cancer Center, Sloan Kettering Institute (SKI

https://www.mskcc.org/research/ski/about

 

Research Programs

Cancer Biology & Genetics Program

Our scientists study the molecular and genetic determinants of cancer predisposition, tumor development, and metastasis.

Cell Biology Program

Our researchers explore the molecular mechanisms that control normal cell behavior and how these mechanisms are disrupted in cancer.

Chemical Biology Program

Our scientists use chemical principles to investigate cutting-edge topics in biology and medicine.

Computational & Systems Biology Program

The goal of our research is to build computer models that simulate biological processes, from the molecular level up to the organism as a whole.

Developmental Biology Program

Our investigators study the mechanisms that control cell proliferation, cell differentiation, tissue patterning, and tissue morphogenesis.

Immunology Program

Our research is geared toward understanding how the immune system functions in all its complexity and how it can be harnessed to fight disease.

Molecular Biology Program

Our research is directed at understanding how cell growth is regulated and how the integrity of the genome is maintained.

Molecular Pharmacology Program

Our research program serves as a conduit for bringing basic science discoveries to preclinical and clinical evaluation.

Structural Biology Program

Our researchers are dedicated to understanding biology at the structural and mechanistic levels, and aiding the development of new cancer therapies.

 

The Dana Pe’er Lab

 

The Dana Pe'er Lab

The Pe’er lab combines single cell technologies, genomic datasets and machine learning algorithms to address fundamental questions in biomedical science. Empowered by recent breakthrough technologies like massive parallel single cell RNA-sequencing, we ask questions such as: How do multi-cellular organisms develop from a single cell, resulting in the vast diversity of progenitor and terminal cell types? How does a cell’s regulatory circuit control the dynamics of signal processing and how do these circuits rewire over the course of development? How does an ensemble of cells function together to execute a multi-cellular response, such as an immune response to pathogen or cancer? We will also address more medically oriented questions such as: How do regulatory circuits go awry in disease? What is the consequence of intra-tumor heterogeneity? Can we characterize the tumor immune eco-system to gain a better understanding of when or why immunotherapy works or does not work? A key goal is to use this characterization of the tumor immune eco-system to personalize immunotherapy.

Dana Pe'er, PhD

Dana Pe’er, PhD

Chair, Computational and Systems Biology Program, SKI; Scientific Director, Metastasis & Tumor Ecosystems Center

Research Focus

Computational Biologist Dana Pe’er combines single cell technologies, genomic datasets and machine learning techniques to address fundamental questions addressing regulatory cell circuits, cellular development, tumor immune eco-system, genotype to phenotype relations and precision medicine.

Education

PhD, Hebrew University, Jerusalem Israel

Contact Information

 

The Dana Pe’er Lab: Publications

View a full listing of Dana Pe’er’s journal articles.

Palantir characterizes cell fate continuities in human hematopoiesis. Setty M, Kiseliovas V, Levine J, Gayoso A, Mazutis L, Pe’er D. 2019, in press. Nature Biotechnology.

Single-cell map of diverse immune phenotypes in the breast tumor microenvironment. Azizi E, Carr AJ, Plitas G, Cornish AE, Konopacki C, Prabhakaran S, Nainys J, Wu K, Kiseliovas V, Setty M, Choi K, Fromme RM, Dao P, McKenney PT, Wasti RC, Kadaveru K, Mazutis L, Rudensky AY, Pe’er D. Cell. 2018 Aug 23;174(5):1293-1308.e36. doi: 10.1016/j.cell.2018.05.060. PMID: 29961579

Recovering gene interactions from single-cell data using data diffusion. van Dijk D, Sharma R, Nainys J, Yim K, Kathail P, Carr AJ, Burdziak C, Moon KR, Chaffer CL, Pattabiraman D, Bierie B, Mazutis L, Wolf G, Krishnaswamy S, Pe’er D. Cell. 2018 Jul 26;174(3):716-729.e27. doi: 10.1016/j.cell.2018.05.061. PubMed PMID: 29961576

The Human Cell Atlas. Regev A et al. Elife. 2017 Dec 5;6. pii: e27041. doi: 10.7554/eLife.27041. PubMed PMID: 29206104

Distinct cellular mechanisms underlie anti-CTLA-4 and anti-PD-1 checkpoint blockade. Wei SC, Levine JH, Cogdill AP, Zhao Y, Anang NAS, Andrews MC, Sharma P, Wang J, Wargo JA, Pe’er D, Allison JP. Cell. 2017 Sep 7;170(6):1120-1133.e17. doi: 10.1016/j.cell.2017.07.024. PMID: 28803728

Wishbone identifies bifurcating developmental trajectories from single-cell data. Setty M, Tadmor MD, Reich-Zeliger S, Angel O, Salame TM, Kathail P, Choi K, Bendall S, Friedman N, Pe’er D. Nat Biotechnol. 2016 Jun;34(6):637-45. doi: 10.1038/nbt.3569. PMID: 27136076

Data-driven phenotypic dissection of AML reveals progenitor-like cells that correlate with prognosis. Levine JH, Simonds EF, Bendall SC, Davis KL, Amir el-AD, Tadmor MD, Litvin O, Fienberg HG, Jager A, Zunder ER, Finck R, Gedman AL, Radtke I, Downing JR, Pe’er D, Nolan GP. Cell. 2015 Jul 2;162(1):184-97. doi: 10.1016/j.cell.2015.05.047. PMID: 26095251

Interferon α/β enhances the cytotoxic response of MEK inhibition in melanoma. Litvin O, Schwartz S, Wan Z, Schild T, Rocco M, Oh NL, Chen BJ, Goddard N, Pratilas C, Pe’er D. Mol Cell. 2015 Mar 5;57(5):784-796. doi: 10.1016/j.molcel.2014.12.030. PMID: 25684207

Integration of genomic data enables selective discovery of breast cancer drivers. Sanchez-Garcia F, Villagrasa P, Matsui J, Kotliar D, Castro V, Akavia UD, Chen BJ, Saucedo-Cuevas L, Rodriguez Barrueco R, Llobet-Navas D, Silva JM, Pe’er D. Cell. 2014 Dec 4;159(6):1461-75. doi: 10.1016/j.cell.2014.10.048. PMID: 25433701

Conditional density-based analysis of T cell signaling in single-cell data. Krishnaswamy S, Spitzer MH, Mingueneau M, Bendall SC, Litvin O, Stone E, Pe’er D, Nolan GP. Systems biology. Science. 2014 Nov 28;346(6213):1250689. doi: 10.1126/science.1250689. PMID: 25342659

Single-cell trajectory detection uncovers progression and regulatory coordination in human B cell development. Bendall SC, Davis KL, Amir el-AD, Tadmor MD, Simonds EF, Chen TJ, Shenfeld DK, Nolan GP, Pe’er D. Cell. 2014 Apr 24;157(3):714-25. doi: 10.1016/j.cell.2014.04.005. PMID: 24766814

SOURCE

https://www.mskcc.org/research/ski/labs/dana-pe-er/publications

Computational biologists combine findings in biology with computer algorithms and databases to conduct biological research on powerful computers, using sophisticated software — so-called “dry” laboratories — in ways that complement and strengthen traditional laboratory and clinical research. The aim is to build computer models that simulate biological processes from the molecular level up to the organism as a whole and to use these models to make useful predictions.

 

Computational biology can help interpret detailed molecular profiles of cancerous and noncancerous cells, molecular response profiles of therapeutic agents, and a person’s genetic profile to assist in the development of better diagnostics and prognostics, as well as improved therapies. Intelligent use of computational methods using detailed molecular and genomic data is expected to reduce the trial and error of drug development and possibly lead to shorter, more accurate clinical trials.

 

The Christina Leslie Lab

The Christina Leslie Lab 

The John Chodera Lab

The John Chodera Lab 

The Dana Pe'er Lab

The Dana Pe’er Lab 

The Joao Xavier Lab

The Joao Xavier Lab 

 

SOURCE

https://www.mskcc.org/research/ski/programs/computational-biology

 

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2019 Wolf Prize in Medicine to Dr. Jeffrey Friedman @RockefellerUniv for Discovery of the Satiety Protein Hormone, Leptin which Regulates the Sensation of Hunger

Posted in Interviews with Scientific Leaders, Obesity, Wolf Prize in Medicine on June 10, 2019| Leave a Comment »


2019 Wolf Prize in Medicine to Dr. Jeffrey Friedman @RockefellerUniv for Discovery of the Satiety Protein Hormone, Leptin which Regulates the Sensation of Hunger

Reporter: Aviva Lev-Ari, PhD, RN

 

Medicine: The satiety hormone

The prize in Medicine will be awarded to Jeffrey Friedman from Rockefeller University in New York, for discovering the hormone leptin, which regulates the sensation of hunger.

Friedman (65) grew up in New York and graduated from medical school at the early age of 22. Later on, he fell in love with research, acquired his PhD in Molecular Genetics, and received a faculty position at Rockefeller. He was interested in understanding the factors that contribute to obesity, and studied a strain of mice with a mutation in a specific gene that made the mice fatter than regular mice. Friedman wanted to understand how a change in just one gene could lead to such an extreme transition, and after eight years of research using the most advanced genetic tools of the time, he identified the gene ob, and later, its product – a protein hormone he termed leptin. He found that leptin, secreted by fat cells into the blood, affects the brain. Under fat shortage leptin levels drop – leading to an increased appetite; while high levels of leptin signal the presence of excess fat and lead to a sensation of fullness, or satiety. Therefore, in certain situations of obesity, leptin treatment may assist in reducing appetite and facilitating weight loss.

Friedman’s studies paved the way for a fuller understanding of the system that regulates hunger and satiety, which has led to the development of new drugs and treatment.

הורמון שחשף את מנגנון ויסות הרעב ושימש לפיתוח טיפולים נגד השמנה. ג'פרי פרידמן | צילום: קרן וולף
A hormone that revealed the mechanism of hunger regulation and served to develop treatments for obesity. Jeffrey Friedman | Photograph: Wolf Foundation
SOURCE

Jeffrey M. Friedman to receive the 2019 Wolf Prize in Medicine

January 16, 2019

Nussenzweig portrait

Jeffrey M. Friedman

Jeffrey M. Friedman, Marilyn M. Simpson Professor and head of Rockefeller’s Laboratory of Molecular Genetics, has been named the recipient of the 2019 Wolf Prize in Medicine. He is being recognized for his discovery of leptin, a hormone secreted by fat cells that modulates food intake and energy expenditure.

Friedman’s 1994 discovery of leptin, and of its receptor in the brain encoded by the obese gene, shed new light on the pathogenesis of obesity. He and his colleagues have since shown that leptin acts on sets of neurons in brain centers that regulate food intake and energy expenditure, and has powerful effects on reproduction, metabolism, other endocrine systems, and immune function. Defects in the leptin gene are associated with severe obesity in animals and humans.

“Jeff’s research has transformed our understanding of obesity. The fact that loss of a single hormone made by fat cells has such a profound effect on our drive to consume calories establishes a biological basis for obesity that is clearly not a simple failure of will-power,” says Rockefeller President Richard P. Lifton. “His research has opened a new field with great potential for advancing health and the understanding of the biological basis of behavior. This prestigious prize is richly deserved.”

Since 1978, the Wolf Foundation in Israel has awarded annual prizes in the arts and sciences, which are presented by the President of Israel. In addition to Friedman’s prize for Medicine, this year’s Wolf Prize recipients include an architect, a professor of agriculture and resource economics, two chemists, and a mathematician. The awardees will be honored at a Jerusalem ceremony led by the Israeli president, Reuven Rivlin, in May.

Previous Rockefeller recipients of the Wolf Prize in Medicine include Maclyn McCarty in 1990 and Jeffrey V. Ravetch in 2015. Three Rockefeller faculty have been recipients of the Wolf Prize in Physics: Mitchell Feigenbaum and Albert Libchaber in 1986 and George Uhlenbeck in 1979.

SOURCE

https://www.rockefeller.edu/news/24785-jeffrey-m-friedman-receive-2019-wolf-prize-medicine/

ALL WOLF PRIZES IN MEDICINE AWARDED

http://www.wolffund.org.il/index.php?dir=site&page=winners&name=&prize=3016&year=&field=3006

The Wolf Prize in Medicine is awarded once a year by the Wolf Foundation in Israel.[1] It is one of the six Wolf Prizes established by the Foundation and awarded since 1978; the others are in Agriculture, Chemistry, Mathematics, Physics and Arts. The Prize has been stated to be the second most prestigious award in science, and a significant predictor of the Nobel Prize.[2]

Table of ALL WOLF PRIZES IN MEDICINE AWARDED, 1978 – 2019

https://en.wikipedia.org/wiki/Wolf_Prize_in_Medicine

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

The Biologic Roles of Leptin in Metabolism, Leptin Physiology and Obesity: On the Mechanism of Action of the Hormone in Energy Balance

Reporter: Aviva Lev-Ari, PhD, RN

 

Leptin signaling in mediating the cardiac hypertrophy associated with obesity

Larry H Bernstein, MD, FCAP, Reviewer, and Aviva Lev-Ari, PhD, RN

 

Leptin and Puberty

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pregnancy with a Leptin-Receptor Mutation

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

New Insights into mtDNA, mitochondrial proteins, aging, and metabolic control

Curator: Larry H. Bernstein, MD, FCAP

Leptin signaling in mediating the cardiac hypertrophy associated with obesity

Larry H Bernstein, MD, FCAP, Reviewer, and Aviva Lev-Ari, PhD, RN

 

Leptin and Puberty

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

Pregnancy with a Leptin-Receptor Mutation

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

 

New Insights into mtDNA, mitochondrial proteins, aging, and metabolic control

Curator: Larry H. Bernstein, MD, FCAP

 

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Real Time Coverage @BIOConvention #BIO2019: Keynote: Siddhartha Mukherjee, Oncologist and Pulitzer Author; June 4 9AM Philadelphia PA

Posted in Cancer - General, Cancer and Current Therapeutics, CANCER BIOLOGY & Innovations in Cancer Therapy, Conference Coverage with Social Media, interventional oncology, Interviews with Scientific Leaders, tagged , , , , , , , , on June 4, 2019| Leave a Comment »


Real Time Coverage @BIOConvention #BIO2019: Keynote: Siddhartha Mukherjee, Oncologist and Pulitzer Author; June 4 9AM Philadelphia PA

Reporter: Stephen J. Williams, PhD. @StephenJWillia2

 

Hematologist and oncologist Siddhartha Mukherjee was born in New Delhi, India. He holds a BS in biology from Stanford University, a DPhil in immunology from Oxford University (where he was a Rhodes Scholar), and an MD from Harvard Medical School. He completed his internal medicine residency and an oncology fellowship at Massachusetts General Hospital. Dr. Murkherjee is an assistant professor of medicine at Columbia University Medical Center. He lives in Manhattan with his wife, artist Sarah Sze, and their two daughters. His Pulitzer Prize-winning book, The Emperor of All Maladies: A Biography of Cancer, tells the story of cancer from its first description in an ancient Egyptian scroll to the gleaming laboratories of modern research institutions. A three-part documentary series based on the book, directed by Barak Goodman and executive produced by Ken Burns, debuts on PBS stations March 30 and continues on March 31 and April 1. The film interweaves a sweeping historical narrative with intimate stories about contemporary patients and an investigation into the latest scientific breakthroughs. He has also written the award winning book “The Gene: An Intimate History” and is Founder of Vor Biopharma, who had just published on their CD33 engineered hematopoetic stem cells as an immunooncology therapy VOR33.

Hon. James C. Greenwood- former Congressional representative and Founder CEO of BIO: moderator

Greenwood: Never have the threats from DC to innovation in the biotech field been so great.  Focused on some great recent innovations and successes in gene therapy.  Although the cost high, father of two LMR retinopathy patients said if his sons had to go through a lifetime of constant care it would cost much more than the gene therapy from Spark cost.  Politicians need to realize that medicines that completely cure diseases are worth much more.  They should meet in the middle with respect to developing a new payer model that will not hurt innovation.

Dr. Mukherjee:  He go into oncology from a virology PhD because he liked to understand the human aspect

of disease.  As an oncologist he gets to interact more closely with patients.  The oncology horizon is always changing.  He likened his view of oncology and cancer as a pyramid with prevention the base, then early detection then therapy at top.

We haven’t found preventable human carcinogens, none that is highly proven causal

This will be the next challenge for cancer researchers, to figure out why we can’t identify these preventable carcinogens.

 

 

 

The link to the PNAS paper on VOR33 can be found here: https://www.pnas.org/content/early/2019/05/23/1819992116

 

Please follow on Twitter using these @ handles and # hashtags

@Handles

@DrSidMukherjee

@pharma_BI

@AVIVA1950

@BIOConvention

# Hashtags

#BIO2019 (official meeting hashtag)

 

Other Articles on this Open Access Journal on Interviews with Scientific Leaders Include:

Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders at https://www.amazon.com/dp/B078313281 – electronic Table of Contents

Jennifer Doudna and NPR science correspondent Joe Palca, several interviews

Practicing Oncology: Medscape Editor-in-Chief Eric J. Topol, MD interviews Siddhartha Mukherjee, MD, PhD

Eric Topol interviews Al Gore on Genomics and Privacy

Dr. Mercola Interviews Dr. Saul About Beta-Blockers

Volume Two: Medical Scientific Discoveries for the 21st Century & Interviews with Scientific Leaders

 

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Real Time Coverage @BIOConvention #BIO2019:  Issues of Risk and Reproduceability in Translational and Academic Collaboration; 2:30-4:00 June 3 Philadelphia PA

Posted in Computational Biology/Systems and Bioinformatics, Conference Coverage with Social Media, Global Partnering & Biotech Investment, Investment in Technological Breakthrough, Life Sciences Breakthrough Prize, Pharmaceutical Discovery, Pharmaceutical Drug Discovery, Pharmaceutical Industry Competitive Intelligence, Pharmaceutical R&D Informatics, Pharmaceutical R&D Investment, tagged , , , , , , , , , , on June 3, 2019| Leave a Comment »


Real Time Coverage @BIOConvention #BIO2019:  Issues of Risk and Reproduceability in Translational and Academic Collaboration; 2:30-4:00 June 3 Philadelphia PA

Reporter: Stephen J. Williams, PhD @StephenJWillia2

Derisking Academic Science: The Unmet Need  

Translating academic research into products and new therapies is a very risky venture as only 1% of academic research has been successfully translated into successful products.

Speakers
Collaboration from Chicago area universities like U of Chicago, Northwestern, etc.  First phase was enhance collaboration between universities by funding faculty recruitment and basic research.  Access to core facilities across universities.  Have expanded to give alternatives to company formation.
Half of the partnerships from Harvard and companies have been able to spin out viable startups.
Most academic PI are not as savvy to start a biotech so they bring in biotechs and build project teams as well as developing a team of ex pharma and biotech experts.  Derisk as running as one asset project.  Partner as early as possible.  A third of their pipeline have been successfully partnered.  Work with investors and patent attorneys.
Focused on getting PIs to get to startup.  Focused on oncology and vaccines and I/O.  The result can be liscensing or partnership. Running around 50 to 60 projects. Creating a new company from these US PI partnerships.
Most projects from Harvard have been therapeutics-based.  At Harvard they have a network of investors ($50 million).   They screen PI proposals based on translateability and what investors are interested in.
In Chicago they solicit multiple projects but are agnostic on area but as they are limited they are focused on projects that will assist in developing a stronger proposal to investor/funding mechanism.
NYU goes around university doing due diligence reaching out to investigators. They shop around their projects to wet their investors, pharma appetite future funding.  At Takeda they have five centers around US.  They want to have more input so go into the university with their scientists and discuss ideas.
Challenges:

Takeda: Data Validation very important. Second there may be disconnect with the amount of equity the PI wants in the new company as well as management.  Third PIs not aware of all steps in drug development.

Harvard:  Pharma and biotech have robust research and academic does not have the size or scope of pharma.  PIs must be more diligent on e.g. the compounds they get from a screen… they only focus narrowly

NYU:  bring in consultants as PIs don’t understand all the management issues.  Need to understand development so they bring in the experts to help them.  Pharma he feels have to much risk aversion and none of their PIs want 100% equity.

Chicago:  they like to publish at early stage so publication freedom is a challenge

It Starts with One Health: A Guide to Translational Science from Research to Investment

115B, Level 100

Speakers
Novel Approaches to Improve Reproducibility in Academia-Industry Collaborations

112AB, Level 100

Speakers
Dr. Freedman: Most scientists responding to Nature survey said yes a reproduceability crisis.  The reasons: experimental bias, lack of validation techniques, reagents, and protocols etc.
And as he says there is a great ECONOMIC IMPACT of preclinical reproducability issues: to the tune of $56 billion of irreproducable results (paper published in PLOS Biology).  If can find the core drivers of this issue they can solve the problem.  STANDARDS are constantly used in various industries however academic research are lagging in developing such standards.  Just the problem of cell line authentication is costing $4 billion.
Dr. Cousins:  There are multiple high throughput screening (HTS) academic centers around the world (150 in US).  So where does the industry go for best practices in assays?  Eli Lilly had developed a manual for HTS best practices and in 1984 made publicly available (Assay Guidance Manual).  To date there have been constant updates to this manual to incorporate new assays.  Workshops have been developed to train scientists in these best practices.
NIH has been developing new programs to address these reproducability issues.  Developed a method called
“Ring Testing Initiative” where multiple centers involved in sharing reagents as well as assays and allowing scientists to test at multiple facilities.
Dr.Tong: Reproduceability of Microarrays:  As microarrays were the only methodology to do high through put genomics in the early 2000s, and although much research had been performed to standardize and achieve best reproduceability of the microarray technology (determining best practices in spotting RNA on glass slides, hybridization protocols, image analysis) little had been done on evaluating the reproducibility of results obtained from microarray experiments involving biological samples.  The advent of Artificial Intelligence and Machine Learning though can be used to help validate microarray results.  This was done in a Nature Biotechnology paper (Nature Biotechnology 28, 827–838 (2010)) by an international consortium, the International MAQC (Microarray Quality Control) Society and can be found here
However Dr. Tong feels there is much confusion in how we define reproduceability.  Dr. Tong identified a few key points of data reproduceability:
  1. Traceability: what are the practices and procedures from going from point A to point B (steps in a protocol or experimental design)
  2. Repeatability:  ability to repeat results within the same laboratory
  3. Replicatablilty:  ability to repeat results cross laboratory
  4. Transferability:  are the results validated across multiple platforms?

The panel then discussed the role of journals and funders to drive reproduceability in research.  They felt that editors have been doing as much as they can do as they receive an end product (the paper) but all agreed funders need to do more to promote data validity, especially in requiring that systematic evaluation and validation of each step in protocols are performed..  There could be more training of PIs with respect to protocol and data validation.

Other Articles on Industry/Academic Research Partnerships and Translational Research on this Open Access Online Journal Include

Envisage-Wistar Partnership and Immunacel LLC Presents at PCCI

BIO Partnering: Intersection of Academic and Industry: BIO INTERNATIONAL CONVENTION June 23-26, 2014 | San Diego, CA

R&D Alliances between Big Pharma and Academic Research Centers: Pharma’s Realization that Internal R&D Groups alone aren’t enough

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2020 Jessie Stevenson Kovalenko Medal for Outstanding Research in the Medical Sciences – Call for Nominations

Posted in Interviews with Scientific Leaders, Jessie Stevenson Kovalenko Medal - Medical Sciences on May 21, 2019| Leave a Comment »


2020 Jessie Stevenson Kovalenko Medal for Outstanding Research in the Medical Sciences – Call for Nominations

 

Reporter: Aviva Lev-Ari, PhD, RN

 

SOURCE

Jessie Stevenson Kovalenko Medal

Scheduled for presentation in 2020.  Nominations accepted online through Monday, October 7, 2019.

About the Jessie Stevenson Kovalenko Medal

The Jessie Stevenson Kovalenko Medal is awarded every two years for outstanding research in the medical sciences. The medal carries with it a $25,000 award, and an additional $50,000 for research. The Kovalenko Fund, gifted by Michael S. Kovalenko in 1949 to the National Academy of Science in memory of his wife, Jessie Stevenson Kovalenko, was specifically designed to recognize the achievements made to the medical sciences and, over the past 67 years, has honored many outstanding contributors.

Most Recent Recipient

James P. Allison, The University of Texas MD Anderson Cancer Center, received the 2018 Jessie Stevenson Kovalenko Medal.

Allison’s pioneering research has had a vast impact on cancer therapy and the evolution of the entire field of cancer immunology. His work has advanced science while improving the health and wellbeing of cancer patients worldwide, a process that continues to this day. Read more about Allison’s work»

Award History

The first Jessie Stevenson Kovalenko Medal was awarded to Alfred N. Richards in 1952 for his outstanding contributions to medical science over a period of a half-century, both as an investigator and as a research executive and administrator. Richards received his first honor in 1897, when he became the first graduate student at Columbia to earn his PhD in physiological chemistry. Richards’ early research focused on the liver and chronic indole poisoning as a possible cause for cyclic vomiting in children although later, he notably sought to study the physiological and ecological effects of the atomic bomb. Richards served as Chairman of the Committee on Medical Research for President Roosevelt and, from 1947-1950, he served as the National Academy of Sciences’ own President, overseeing the establishment of the National Science Foundation.

Recipients:

James P. Allison (2018)
For the discovery that antibody blockade of the T cell molecule CTLA-4 unleashes the body’s immune response against malignant tumors and develops immune checkpoint blockade as a successful cancer therapy.
Read more about Allison’s work»
Watch Allison’s acceptance speech»

Huda Y. Zoghbi (2016)
For her pioneering contributions to the fields of neurodegenerative proteinopathies, autism spectrum disorders, epigenetics, and developmental biology by coupling clinical observation and gene discovery with focused, in-depth mechanistic study.
Read more about Zoghbi’s work»

Stuart H. Orkin (2013)
For his pioneering achievements in defining the molecular basis of blood disorders and the mechanisms governing the development of blood stem cells and individual blood lineages. His work has significantly advanced our understanding of human hematologic diseases and revealed new strategies to prevent and manage these disorders.
 
For her discovery of recurring chromosome translocations that characterize specific hematological malignancies, a landmark event that caused a major shift in the paradigms relating to cancer biology in the 1970s and paved the way for development of specific treatment for two leukemias.
 
Jeffrey M. Friedman (2007)
For the discovery of leptin and its role in the regulation of appetite, energy expenditure, and the molecular mechanisms underlying obesity.
 
Irving L. Weissman (2004)
For his seminal studies that defined the physical properties, purification, and growth regulation of multipotent hematopoietic stem cells.
 
For his elucidation of the structure, function, and mechanism of regulation of heptahelical receptors, nature’s detectors of signals from many hormones, neurotransmitters, and drugs.
 
For his landmark discovery and identification of genes that control immune responsiveness, and for his subsequent elucidation of mechanisms of antigen recognition and induction of the immune response.
 
For his discovery and purification of the hemotopoietic growth factors and for their introduction into clinical medicine for the control of blood cell formation and resistance to infection.
 
For revolutionary accomplishments in human sphingolipid storage disorders, including the discovery of enzymatic defects, the development of genetic counseling procedures, and successful enzyme-replacement therapy.
 
For the discovery and characterization, with Avery and McLeod, that deoxyribonucleic acid is the chemical substance of heredity, and for his subsequent contributions to our understanding of the biology of streptococci and their role in disease.
 
Oscar D. Ratnoff (1985)
For his studies of the Hageman trait, an experiment of nature that improved understanding of such bodily defenses as the formation and dissolution of blood clots, inflammation, and immunity.
 
Henry G. Kunkel (1979)
For his pioneering and influential studies in basic immunology, immune complex disease, immune deficiency disorders, and lymphocytic membrane markers.
 
Julius H. Comroe, Jr. (1976)
For his immeasurable contribution to the diagnosis and treatment of human disease during his career, which was devoted to the physiology and chemistry of respiration and the mechanical and chemical properties of the human lung.
 
Seymour S. Kety (1973)
For furthering the essential understanding of balance between hereditary and other biological factors, on the one hand, and psychosocial experimental ones, on the other, in the pathogenesis and manifestations of schizophrenia.
 
For his laboratory and epidemiological researches on virus diseases, including his major role in the program for the evaluation of the polio vaccine and for his imaginative design for long-term studies of the atomic bomb survivors in Japan.
 
Karl P. Link (1967)
For his discovery and application of coumarin anticoagulants.
 
Rufus Cole (1966)
For his notable role in advancing our knowledge of lobar pneumonia and in establishing clinical investigation as a science.
 
George H. Whipple (1962)
For his contributions of many biological discoveries basic for advances in clinical and experimental medicine.
 
Karl F. Meyer (1961)
For his outstanding contributions to medical sciences as an investigator, teacher, and administrator over a period of half a century.
 
Eugene L. Opie (1959)
For his outstanding contributions to medical science and for a life of exemplary devotion to medical education and inquiry into the origins of disease.
 
Ernest W. Goodpasture (1958)
For his outstanding contributions to medical science and for long and continued devotion to the study of his chosen field of pathology.
 
Peyton Rous (1955)
 
Alfred N. Richards (1952)
For his outstanding contributions to medical science over a period of a half-century, both as an investigator and as a research executive and administrator.

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Mechanism of Platelet Granule Release and its Role in Thrombus Formation: Lead Contributor to discoveries, Robert Flaumenhaft, MD, PhD, Division of Hemostasis and Thrombosis at BIDMC and Harvard Medical School

Posted in Coagulation Therapy and Internal Bleeding, Interviews with Scientific Leaders on May 1, 2019| Leave a Comment »


Mechanism of Platelet Granule Release and its Role in Thrombus Formation: Lead Contributor to discoveries, Robert Flaumenhaft, MD, PhD, Division of Hemostasis and Thrombosis at BIDMC and Harvard Medical School

Reporter: Aviva Lev-Ari, PhD, RN

 

It is well known that platelets are crucial for stopping bleeding. Platelets prevent excessive posttraumatic blood loss at sites of vascular injury by forming a platelet plug. Upon exposure of the subendothelial extracellular matrix, platelets are recruited to the site of injury and become activated, resulting in firm adhesion and subsequent platelet aggregation. The molecular mechanisms underlying the formation of a hemostatic platelet plug are relatively well understood: upon exposure of the subendothelial matrix, platelets either interact directly with matrix proteins (eg, via glycoprotein VI [GPVI] and α2β1 to collagen) or bind to von Willebrand factor (VWF) that is deposited at the site of injury. Transient interactions between platelet GPIb and VWF support platelet tethering at sites of high shear stress. Firm adhesion and subsequent aggregation is mediated by activated integrin receptors such as αIIbβ3. G-protein–coupled receptors mediate activation signals after being triggered by soluble agonists such as thrombin, thromboxane A2, and adenosine 5′-diphosphate, which reinforce thrombus propagation.

SOURCE

Simon F. De Meyer
Blood 2017 129:1573-1574; doi: https://doi.org/10.1182/blood-2017-02-763540

http://www.bloodjournal.org/content/129/12/1573?sso-checked=true

To address the role of platelet granule content in maintaining vascular integrity in inflammation, Deppermann et al generated Unc13d−/−/Nbeal2−/− mice.1 Platelets from these mice are unable to secrete their α- or dense-granule content. The authors used these mice in models of lung inflammation, skin inflammation, and brain infarction. Similar to previous studies, intradermal hemorrhage was observed in platelet-depleted wild-type (WT) mice at the site of inflammation. Strikingly, no bleeding was observed in the inflamed skin of Unc13d−/−/Nbeal2−/− mice. Analogous results were observed in lung inflammation. These experiments show that release of α or dense granules is not necessary to maintain vascular integrity at sites of acute inflammation in skin and lung. Much different results were however obtained in the stroke model used by the authors. Indeed, when subjected to transient middle cerebral artery occlusion, Unc13d−/−/Nbeal2−/− mice were prone to intracranial bleeding in the infarcted areas. Cerebral hemorrhage in these mice resulted in a significantly increased mortality compared with WT animals. In an elegant approach using platelet transfusion experiments, the authors showed that the observed effects of combined Munc13-4 and Nbeal deficiency were related to the platelet-specific secretion effects and not to potential defects in other cells.

SOURCE

Simon F. De Meyer
Blood 2017 129:1573-1574; doi: https://doi.org/10.1182/blood-2017-02-763540

http://www.bloodjournal.org/content/129/12/1573?sso-checked=true

 

Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis

Ejaife O. Agbani and Alastair W. Poole
Blood 2017 130:2171-2179; doi: https://doi.org/10.1182/blood-2017-05-787259

Abstract

Current understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range of descriptive titles and attributes. We identify striking overlaps in the reported characteristics of these platelets, which imply a single subpopulation of versatile platelets and thus suggest that their commonality requires unification of their description. We therefore propose the term procoagulant platelet as the unifying terminology. We discuss the agonist requirements and molecular drivers for the dramatic morphological transformation platelets undergo when becoming procoagulant. Finally, we provide perspectives on the biomarker potential of procoagulant platelets for thrombotic events as well as on the possible clinical benefits of inhibitors of carbonic anhydrase enzymes and the water channel Aquaporin-1 for targeting this subpopulation of platelets as antiprocoagulant antithrombotics.

SOURCE

http://www.bloodjournal.org/content/130/20/2171

Robert Flaumenhaft, MD, PhD – A Biography

https://www.bidmc.org/research/research-by-department/medicine/hemostasis-and-thrombosis/flaumenhaft-lab/biography

Most cited
 2009 Jul;23(4):177-89. doi: 10.1016/j.blre.2009.04.001. Epub 2009 May 17.

Platelet alpha-granules: basic biology and clinical correlates.

Blair P1, Flaumenhaft R.

Abstract

alpha-Granules are essential to normal platelet activity. These unusual secretory granules derive their cargo from both regulated secretory and endocytotic pathways in megakaryocytes. Rare, inheritable defects of alpha-granule formation in mice and man have enabled identification of proteins that mediate cargo trafficking and alpha-granule formation. In platelets, alpha-granules fuse with the plasma membrane upon activation, releasing their cargo and increasing platelet surface area. The mechanisms that control alpha-granule membrane fusion have begun to be elucidated at the molecular level. SNAREs and SNARE accessory proteins that control alpha-granule secretion have been identified. Proteomic studies demonstrate that hundreds of bioactive proteins are released from alpha-granules. This breadth of proteins implies a versatile functionality. While initially known primarily for their participation in thrombosis and hemostasis, the role of alpha-granules in inflammation, atherosclerosis, antimicrobial host defense, wound healing, angiogenesis, and malignancy has become increasingly appreciated as the function of platelets in the pathophysiology of these processes has been defined. This review will consider the formation, release, and physiologic roles of alpha-granules with special emphasis on work performed over the last decade.

PMID:
19450911
PMCID:
PMC2720568
DOI:
10.1016/j.blre.2009.04.001

SOURCE

https://www.ncbi.nlm.nih.gov/pubmed/19450911

 

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    Translation:HumansAnimalsCells

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    Translation:HumansAnimalsCells

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    Translation:HumansAnimals

  • Stopa JD, Baker KM, Grover SP, Flaumenhaft R, Furie B. Kinetic-based trapping by intervening sequence variants of the active sites of protein-disulfide isomerase identifies platelet protein substrates. J Biol Chem. 2017 06 02; 292(22):9063-9074. PMID: 28364042.

    Citations: 3   Fields:

    Translation:HumansCells

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    Translation:HumansCells

  • Stopa JD, Neuberg D, Puligandla M, Furie B, Flaumenhaft R, Zwicker JI. Protein disulfide isomerase inhibition blocks thrombin generation in humans by interfering with platelet factor V activation. JCI Insight. 2017 01 12; 2(1):e89373. PMID: 28097231.

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    18 readers on Mendeley

     

  • Schiemer J, Bohm A, Lin L, Merrill-Skoloff G, Flaumenhaft R, Huang JS, Le Breton GC, Chishti AH. Ga13 Switch Region 2 Relieves Talin Autoinhibition to Activate aIIbß3 Integrin. J Biol Chem. 2016 Dec 23; 291(52):26598-26612. PMID: 27803165.

    Citations: 4  

    14 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Young platelets out-of-control. Thromb Haemost. 2016 10 28; 116(5):780. PMID: 27683761.

    Citations: 

    1 reader on Mendeley

     

    Translation:HumansCells

  • Atefi G, Aisiku O, Shapiro N, Hauser C, Dalle Lucca J, Flaumenhaft R, Tsokos GC. Complement Activation in Trauma Patients Alters Platelet Function. Shock. 2016 09; 46(3 Suppl 1):83-8. PMID: 27355402.

    Citations: 2  

    9 readers on Mendeley

     

    Translation:HumansCells

  • Bekendam RH, Bendapudi PK, Lin L, Nag PP, Pu J, Kennedy DR, Feldenzer A, Chiu J, Cook KM, Furie B, Huang M, Hogg PJ, Flaumenhaft R. A substrate-driven allosteric switch that enhances PDI catalytic activity. Nat Commun. 2016 08 30; 7:12579.PMID: 27573496.

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    37 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Flaumenhaft R. SERCAmnavigating calcium signaling in platelets. Blood. 2016 08 25; 128(8):1034-5. PMID: 27563149.

    Fields:

    Translation:HumansCells

  • Flaumenhaft R, Furie B. Vascular thiol isomerases. Blood. 2016 08 18; 128(7):893-901. PMID: 27357699.

    Citations: 8  

    28 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Gong L, Proulle V, Fang C, Hong Z, Lin Z, Liu M, Xue G, Yuan C, Lin L, Furie B, Flaumenhaft R, Andreasen P, Furie B, Huang M. A specific plasminogen activator inhibitor-1 antagonist derived from inactivated urokinase. J Cell Mol Med. 2016 10; 20(10):1851-60. PMID: 27197780.

    Citations: 1  

    9 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Bekendam RH, Flaumenhaft R. Inhibition of Protein Disulfide Isomerase in Thrombosis. Basic Clin Pharmacol Toxicol. 2016 Oct; 119 Suppl 3:42-48. PMID: 26919268.

    Citations: 3   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Probing for thiol isomerase activity in thrombi. J Thromb Haemost. 2016 05; 14(5):1067-9. PMID: 26854753.

    Fields:

    Translation:Humans

  • Jain A, Graveline A, Waterhouse A, Vernet A, Flaumenhaft R, Ingber DE. A shear gradient-activated microfluidic device for automated monitoring of whole blood haemostasis and platelet function. Nat Commun. 2016 Jan 06; 7:10176. PMID: 26733371.

    Citations: 13  

    156 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Schulman S, Bendapudi P, Sharda A, Chen V, Bellido-Martin L, Jasuja R, Furie BC, Flaumenhaft R, Furie B. Extracellular Thiol Isomerases and Their Role in Thrombus Formation. Antioxid Redox Signal. 2016 Jan 01; 24(1):1-15. PMID: 26467859.

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    31 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Lin L, Gopal S, Sharda A, Passam F, Bowley SR, Stopa J, Xue G, Yuan C, Furie BC, Flaumenhaft R, Huang M, Furie B. Quercetin-3-rutinoside Inhibits Protein Disulfide Isomerase by Binding to Its b’x Domain. J Biol Chem. 2015 Sep 25; 290(39):23543-52. PMID: 26240139.

    Citations: 11   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R. A new story ARC for a-granule formation. Blood. 2015 Jul 09; 126(2):123-4. PMID: 26160182.

    Citations: 

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    Translation:HumansAnimalsCells

  • Koseoglu S, Peters CG, Fitch-Tewfik JL, Aisiku O, Danglot L, Galli T, Flaumenhaft R. VAMP-7 links granule exocytosis to actin reorganization during platelet activation. Blood. 2015 Jul 30; 126(5):651-60. PMID: 25999457.

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    Translation:HumansAnimalsCells

  • Sakurai Y, Fitch-Tewfik JL, Qiu Y, Ahn B, Myers DR, Tran R, Fay ME, Ding L, Spearman PW, Michelson AD, Flaumenhaft R, Lam WA. Platelet geometry sensing spatially regulates a-granule secretion to enable matrix self-deposition. Blood. 2015 Jul 23; 126(4):531-8. PMID: 25964667.

    Citations: 2   Fields:

    Translation:HumansCells

  • Sharda A, Kim SH, Jasuja R, Gopal S, Flaumenhaft R, Furie BC, Furie B. Defective PDI release from platelets and endothelial cells impairs thrombus formation in Hermansky-Pudlak syndrome. Blood. 2015 Mar 05; 125(10):1633-42. PMID: 25593336.

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    Translation:HumansAnimalsCells

  • Aisiku O, Peters CG, De Ceunynck K, Ghosh CC, Dilks JR, Fustolo-Gunnink SF, Huang M, Dockendorff C, Parikh SM, Flaumenhaft R. Parmodulins inhibit thrombus formation without inducing endothelial injury caused by vorapaxar. Blood. 2015 Mar 19; 125(12):1976-85. PMID: 25587041.

    Citations: 11   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Making (anti)sense of factor XI in thrombosis. N Engl J Med. 2015 Jan 15; 372(3):277-8. PMID: 25482334.

    Citations: 1  

    27 readers on Mendeley

    Translation:Humans

  • Flaumenhaft R. Thrombus formation reimagined. Blood. 2014 Sep 11; 124(11):1697-8. PMID: 25214193.

    Citations: 2   Fields:

    Translation:HumansAnimals

  • Flaumenhaft R, Furie B, Zwicker JI. Therapeutic implications of protein disulfide isomerase inhibition in thrombotic disease. Arterioscler Thromb Vasc Biol. 2015 Jan; 35(1):16-23. PMID: 25104801.

    Citations: 19  

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    Translation:HumansAnimalsCells

  • Furie B, Flaumenhaft R. Thiol isomerases in thrombus formation. Circ Res. 2014 Mar 28; 114(7):1162-73. PMID: 24677236.

    Citations: 23  

    41 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Bioengineering in platelet biology. Thromb Res. 2014 Apr; 133(4):523-4. PMID: 24433610.

    Fields:

    Translation:HumansAnimalsCells

  • Battinelli EM, Markens BA, Kulenthirarajan RA, Machlus KR, Flaumenhaft R, Italiano JE. Anticoagulation inhibits tumor cell-mediated release of platelet angiogenic proteins and diminishes platelet angiogenic response. Blood. 2014 Jan 02; 123(1):101-12. PMID: 24065244.

    Citations: 26   Fields:

    Translation:HumansCells

  • Koseoglu S, Flaumenhaft R. Advances in platelet granule biology. Curr Opin Hematol. 2013 Sep; 20(5):464-71. PMID: 23839294.

    Citations: 19  

    40 readers on Mendeley

     

    Translation:HumansCells

  • Fitch-Tewfik JL, Flaumenhaft R. Platelet granule exocytosis: a comparison with chromaffin cells. Front Endocrinol (Lausanne). 2013; 4:77. PMID: 23805129.

    Citations: 9  

    65 readers on Mendeley

     

  • Flaumenhaft R. Protein disulfide isomerase as an antithrombotic target. Trends Cardiovasc Med. 2013 Oct; 23(7):264-8. PMID: 23541171.

    Citations: 10  

    20 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Koseoglu S, Dilks JR, Peters CG, Fitch-Tewfik JL, Fadel NA, Jasuja R, Italiano JE, Haynes CL, Flaumenhaft R. Dynamin-related protein-1 controls fusion pore dynamics during platelet granule exocytosis. Arterioscler Thromb Vasc Biol. 2013 Mar; 33(3):481-8. PMID: 23288151.

    Citations: 12  

    36 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Flaumenhaft R. a-granules: a story in the making. Blood. 2012 Dec 13; 120(25):4908-9. PMID: 23243155.

    Citations: 1  

    23 readers on Mendeley

    Translation:HumansCells

  • Flaumenhaft R. Monitoring granule traffic in megakaryocytes. Blood. 2012 Nov 08; 120(19):3869-70. PMID: 23144159.

    Fields:

    Translation:HumansCells

  • Thon JN, Peters CG, Machlus KR, Aslam R, Rowley J, Macleod H, Devine MT, Fuchs TA, Weyrich AS, Semple JW, Flaumenhaft R, Italiano JE. T granules in human platelets function in TLR9 organization and signaling. J Cell Biol. 2012 Aug 20; 198(4):561-74. PMID: 22908309.

    Citations: 36  

    82 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Peters CG, Michelson AD, Flaumenhaft R. Granule exocytosis is required for platelet spreading: differential sorting of a-granules expressing VAMP-7. Blood. 2012 Jul 05; 120(1):199-206. PMID: 22589474.

    Citations: 23   Fields:

    Translation:HumansAnimalsCells

  • Jasuja R, Passam FH, Kennedy DR, Kim SH, van Hessem L, Lin L, Bowley SR, Joshi SS, Dilks JR, Furie B, Furie BC, Flaumenhaft R. Protein disulfide isomerase inhibitors constitute a new class of antithrombotic agents. J Clin Invest. 2012 Jun; 122(6):2104-13. PMID: 22565308.

    Citations: 57  

    90 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Ashitate Y, Kim SH, Tanaka E, Henary M, Choi HS, Frangioni JV, Flaumenhaft R. Two-wavelength near-infrared fluorescence for the quantitation of drug antiplatelet effects in large animal model systems. J Vasc Surg. 2012 Jul; 56(1):171-80. PMID: 22503225.

    Citations: 9   Fields:

    Translation:HumansAnimalsCells

  • Dockendorff C, Aisiku O, Verplank L, Dilks JR, Smith DA, Gunnink SF, Dowal L, Negri J, Palmer M, Macpherson L, Schreiber SL, Flaumenhaft R. Discovery of 1,3-Diaminobenzenes as Selective Inhibitors of Platelet Activation at the PAR1 Receptor. ACS Med Chem Lett. 2012 Mar 08; 3(3):232-237. PMID: 22408714.

    Citations: 10  

    27 readers on Mendeley

     

  • Flaumenhaft R. Platelets get the message. Blood. 2011 Aug 18; 118(7):1712-3. PMID: 21852441.

    Citations: 1  

    17 readers on Mendeley

     

  • Dowal L, Yang W, Freeman MR, Steen H, Flaumenhaft R. Proteomic analysis of palmitoylated platelet proteins. Blood. 2011 Sep 29; 118(13):e62-73. PMID: 21813449.

    Citations: 34   Fields:

    Translation:HumansCells

  • Nachtigall MJ, Jessel RH, Flaumenhaft R, Nachtigall R, Yoles I, Naftolin F, Nachtigall LE. The selective estrogen receptor modulator DT56a (Femarelle) does not affect platelet reactivity in normal or thrombophilic postmenopausal women. Menopause. 2011 Mar; 18(3):285-8. PMID: 21037489.

    Citations: 1   Fields:

    Translation:HumansCells

  • Dowal L, Sim DS, Dilks JR, Blair P, Beaudry S, Denker BM, Koukos G, Kuliopulos A, Flaumenhaft R. Identification of an antithrombotic allosteric modulator that acts through helix 8 of PAR1. Proc Natl Acad Sci U S A. 2011 Feb 15; 108(7):2951-6.PMID: 21282664.

    Citations: 25   Fields:

    Translation:AnimalsCells

  • Liu J, Gao BB, Clermont AC, Blair P, Chilcote TJ, Sinha S, Flaumenhaft R, Feener EP. Hyperglycemia-induced cerebral hematoma expansion is mediated by plasma kallikrein. Nat Med. 2011 Feb; 17(2):206-10. PMID: 21258336.

    Citations: 38  

    68 readers on Mendeley

    Translation:Animals

  • Flaumenhaft R. Filling a void in Gray Platelets. Blood. 2010 Dec 02; 116(23):4738-40. PMID: 21127182.

    Citations: 1   Fields:

  • Flaumenhaft R, Mairuhu AT, Italiano JE. Platelet- and megakaryocyte-derived microparticles. Semin Thromb Hemost. 2010 Nov; 36(8):881-7. PMID: 21049389.

    Citations: 10   Fields:

    Translation:HumansCells

  • Italiano JE, Mairuhu AT, Flaumenhaft R. Clinical relevance of microparticles from platelets and megakaryocytes. Curr Opin Hematol. 2010 Nov; 17(6):578-84. PMID: 20739880.

    Citations: 56   Fields:

    Translation:HumansAnimalsCells

  • Woronowicz K, Dilks JR, Rozenvayn N, Dowal L, Blair PS, Peters CG, Woronowicz L, Flaumenhaft R. The platelet actin cytoskeleton associates with SNAREs and participates in alpha-granule secretion. Biochemistry. 2010 Jun 01; 49(21):4533-42.PMID: 20429610.

    Citations: 17   Fields:

    Translation:HumansCells

  • Dowal L, Flaumenhaft R. Targeting platelet G-protein coupled receptors (GPCRs): looking beyond conventional GPCR antagonism. Curr Vasc Pharmacol. 2010 Mar; 8(2):140-54. PMID: 19485898.

    Citations: 8   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Getting in shape with RanBP10. Blood. 2009 Dec 24; 114(27):5412-3. PMID: 20035043.

    Citations: 1   Fields:

  • Tanaka E, Chen FY, Flaumenhaft R, Graham GJ, Laurence RG, Frangioni JV. Real-time assessment of cardiac perfusion, coronary angiography, and acute intravascular thrombi using dual-channel near-infrared fluorescence imaging. J Thorac Cardiovasc Surg. 2009 Jul; 138(1):133-40. PMID: 19577070.

    Citations: 24  

    26 readers on Mendeley

    Translation:Animals

  • Blair P, Flaumenhaft R. Platelet alpha-granules: basic biology and clinical correlates. Blood Rev. 2009 Jul; 23(4):177-89. PMID: 19450911.

    Citations: 144  

    352 readers on Mendeley
    2 readers on CiteULike

     

    Translation:HumansAnimalsCells

  • Graham GJ, Ren Q, Dilks JR, Blair P, Whiteheart SW, Flaumenhaft R. Endobrevin/VAMP-8-dependent dense granule release mediates thrombus formation in vivo. Blood. 2009 Jul 30; 114(5):1083-90. PMID: 19395672.

    Citations: 34   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Nachtigall M, Lowenstein J, Nachtigall L, Nachtigall R, Nachtigall L. Association of oral but not transdermal estrogen therapy with enhanced platelet reactivity in a subset of postmenopausal women. Menopause. 2009 Mar-Apr; 16(2):407-12. PMID: 18989235.

    Citations: 2   Fields:

    Translation:HumansCells

  • Flaumenhaft R, Dilks JR, Richardson J, Alden E, Patel-Hett SR, Battinelli E, Klement GL, Sola-Visner M, Italiano JE. Megakaryocyte-derived microparticles: direct visualization and distinction from platelet-derived microparticles. Blood. 2009 Jan 29; 113(5):1112-21. PMID: 18802008.

    Citations: 52  

    129 readers on Mendeley

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Dilks JR. Discovery-based strategies for studying platelet function. Mini Rev Med Chem. 2008 Apr; 8(4):350-7.PMID: 18473926.

    Citations: 2   Fields:

    Translation:HumansCells

  • Dilks JR, Flaumenhaft R. Fluoxetine (Prozac) augments platelet activation mediated through protease-activated receptors. J Thromb Haemost. 2008 Apr; 6(4):705-8. PMID: 18194419.

    Citations: 3   Fields:

    Translation:HumansCells

  • Flaumenhaft R, Rozenvayn N, Feng D, Dvorak AM. SNAP-23 and syntaxin-2 localize to the extracellular surface of the platelet plasma membrane. Blood. 2007 Sep 01; 110(5):1492-501. PMID: 17485553.

    Citations: 5  

    38 readers on Mendeley

     

    Translation:HumansCellsCT

  • Sim DS, Dilks JR, Flaumenhaft R. Platelets possess and require an active protein palmitoylation pathway for agonist-mediated activation and in vivo thrombus formation. Arterioscler Thromb Vasc Biol. 2007 Jun; 27(6):1478-85. PMID: 17303775.

    Citations: 12  

    24 readers on Mendeley

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Tanaka E, Graham GJ, De Grand AM, Laurence RG, Hoshino K, Hajjar RJ, Frangioni JV. Localization and quantification of platelet-rich thrombi in large blood vessels with near-infrared fluorescence imaging. Circulation. 2007 Jan 02; 115(1):84-93. PMID: 17179017.

    Citations: 15  

    30 readers on Mendeley

     

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Formation and fate of platelet microparticles. Blood Cells Mol Dis. 2006 Mar-Apr; 36(2):182-7. PMID: 16466949.

    Citations: 32   Fields:

    Translation:HumansCells

  • Flaumenhaft R, Lo EH. Different strokes for rodent folks. Nat Methods. 2006 Feb; 3(2):79-80. PMID: 16432514.

    Citations: 1   Fields:

    Translation:Animals

  • Flaumenhaft R, Sim DS. Protein palmitoylation in signal transduction of hematopoietic cells. Hematology. 2005 Dec; 10(6):511-9.PMID: 16321817.

    Citations: 2   Fields:

    Translation:HumansAnimalsCells

  • O’Connell DJ, Rozenvayn N, Flaumenhaft R. Phosphatidylinositol 4,5-bisphosphate regulates activation-induced platelet microparticle formation. Biochemistry. 2005 Apr 26; 44(16):6361-70. PMID: 15835925.

    Citations: 5   Fields:

    Translation:HumansCells

  • Sim D, Flaumenhaft R, Furie B, Furie B. Interactions of platelets, blood-borne tissue factor, and fibrin during arteriolar thrombus formation in vivo. Microcirculation. 2005 Apr-May; 12(3):301-11. PMID: 15814438.

    Citations: 9   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Dilks JR, Rozenvayn N, Monahan-Earley RA, Feng D, Dvorak AM. The actin cytoskeleton differentially regulates platelet alpha-granule and dense-granule secretion. Blood. 2005 May 15; 105(10):3879-87. PMID: 15671445.

    Citations: 29   Fields:

    Translation:HumansCells

  • Falati S, Gross PL, Merrill-Skoloff G, Sim D, Flaumenhaft R, Celi A, Furie BC, Furie B. In vivo models of platelet function and thrombosis: study of real-time thrombus formation. Methods Mol Biol. 2004; 272:187-97. PMID: 15226545.

    Citations: 12   Fields:

    Translation:AnimalsCells

  • Flaumenhaft R. Platelet permeabilization. Methods Mol Biol. 2004; 273:365-78. PMID: 15308812.

    Citations: 1   Fields:

    Translation:HumansCells

  • Sim DS, Merrill-Skoloff G, Furie BC, Furie B, Flaumenhaft R. Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels. Blood. 2004 Mar 15; 103(6):2127-34. PMID: 14645013.

    Citations: 20   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Sim DS. The platelet as a model for chemical genetics. Chem Biol. 2003 Jun; 10(6):481-6. PMID: 12837380.

    Citations: 2   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R. Molecular basis of platelet granule secretion. Arterioscler Thromb Vasc Biol. 2003 Jul 01; 23(7):1152-60. PMID: 12738684.

    Citations: 30   Fields:

    Translation:Cells

  • Lai KC, Flaumenhaft R. SNARE protein degradation upon platelet activation: calpain cleaves SNAP-23. J Cell Physiol. 2003 Feb; 194(2):206-14. PMID: 12494459.

    Citations: 5   Fields:

    Translation:HumansCells

  • Celi A, Merrill-Skoloff G, Gross P, Falati S, Sim DS, Flaumenhaft R, Furie BC, Furie B. Thrombus formation: direct real-time observation and digital analysis of thrombus assembly in a living mouse by confocal and widefield intravital microscopy. J Thromb Haemost. 2003 Jan; 1(1):60-8. PMID: 12871540.

    Citations: 25   Fields:

    Translation:AnimalsCells

  • Rozenvayn N, Flaumenhaft R. Protein kinase C mediates translocation of type II phosphatidylinositol 5-phosphate 4-kinase required for platelet alpha-granule secretion. J Biol Chem. 2003 Mar 07; 278(10):8126-34. PMID: 12509423.

    Citations: 8  

    17 readers on Mendeley

    Translation:HumansCells

  • Feng D, Crane K, Rozenvayn N, Dvorak AM, Flaumenhaft R. Subcellular distribution of 3 functional platelet SNARE proteins: human cellubrevin, SNAP-23, and syntaxin 2. Blood. 2002 Jun 01; 99(11):4006-14. PMID: 12010801.

    Citations: 24   Fields:

    Translation:HumansCells

  • Furie B, Furie BC, Flaumenhaft R. A journey with platelet P-selectin: the molecular basis of granule secretion, signalling and cell adhesion. Thromb Haemost. 2001 Jul; 86(1):214-21. PMID: 11487009.

    Citations: 33   Fields:

    Translation:HumansCells

  • Rozenvayn N, Flaumenhaft R. Phosphatidylinositol 4,5-bisphosphate mediates Ca2+-induced platelet alpha-granule secretion: evidence for type II phosphatidylinositol 5-phosphate 4-kinase function. J Biol Chem. 2001 Jun 22; 276(25):22410-9. PMID: 11304526.

    Citations: 6   Fields:

    Translation:HumansCells

  • Feng D, Flaumenhaft R, Bandeira-Melo C, Weller P, Dvorak A. Ultrastructural localization of vesicle-associated membrane protein(s) to specialized membrane structures in human pericytes, vascular smooth muscle cells, endothelial cells, neutrophils, and eosinophils. J Histochem Cytochem. 2001 Mar; 49(3):293-304. PMID: 11181732.

    Citations: 12   Fields:

    Translation:HumansCells

  • Yang J, Hirata T, Croce K, Merrill-Skoloff G, Tchernychev B, Williams E, Flaumenhaft R, Furie BC, Furie B. Targeted gene disruption demonstrates that P-selectin glycoprotein ligand 1 (PSGL-1) is required for P-selectin-mediated but not E-selectin-mediated neutrophil rolling and migration. J Exp Med. 1999 Dec 20; 190(12):1769-82. PMID: 10601352.

    Citations: 70  

    53 readers on Mendeley

     

    Translation:AnimalsCells

  • Croce K, Flaumenhaft R, Rivers M, Furie B, Furie BC, Herman IM, Potter DA. Inhibition of calpain blocks platelet secretion, aggregation, and spreading. J Biol Chem. 1999 Dec 17; 274(51):36321-7. PMID: 10593923.

    Citations: 22   Fields:

    Translation:HumansCells

  • Flaumenhaft R, Furie B, Furie BC. Alpha-granule secretion from alpha-toxin permeabilized, MgATP-exposed platelets is induced independently by H+ and Ca2+. J Cell Physiol. 1999 Apr; 179(1):1-10. PMID: 10082126.

    Citations: 4   Fields:

    Translation:HumansCells

  • Flaumenhaft R, Croce K, Chen E, Furie B, Furie BC. Proteins of the exocytotic core complex mediate platelet alpha-granule secretion. Roles of vesicle-associated membrane protein, SNAP-23, and syntaxin 4. J Biol Chem. 1999 Jan 22; 274(4):2492-501. PMID: 9891020.

    Citations: 31   Fields:

    Translation:HumansCells

  • Thorpe CM, Flaumenhaft R, Hurley B, Jacewicz M, Acheson DW, Keusch GT. Shiga toxins do not directly stimulate alpha-granule secretion or enhance aggregation of human platelets. Acta Haematol. 1999; 102(1):51-5. PMID: 10473889.

    Citations: 4   Fields:

    Translation:HumansCellsCT

  • Flaumenhaft R, Abe M, Sato Y, Miyazono K, Harpel J, Heldin CH, Rifkin DB. Role of the latent TGF-beta binding protein in the activation of latent TGF-beta by co-cultures of endothelial and smooth muscle cells. J Cell Biol. 1993 Feb; 120(4):995-1002.PMID: 8432736.

    Citations: 46  

    35 readers on Mendeley

     

    Translation:AnimalsCells

  • Flaumenhaft R, Kojima S, Abe M, Rifkin DB. Activation of latent transforming growth factor beta. Adv Pharmacol. 1993; 24:51-76. PMID: 8504067.

    Citations: 20   Fields:

    Translation:HumansAnimals

  • Flaumenhaft R, Rifkin DB. The extracellular regulation of growth factor action. Mol Biol Cell. 1992 Oct; 3(10):1057-65. PMID: 1421565.

    Citations: 32   Fields:

    Translation:HumansAnimalsCells

  • Flaumenhaft R, Abe M, Mignatti P, Rifkin DB. Basic fibroblast growth factor-induced activation of latent transforming growth factor beta in endothelial cells: regulation of plasminogen activator activity. J Cell Biol. 1992 Aug; 118(4):901-9. PMID: 1380001.

    Citations: 35  

    23 readers on Mendeley

    Translation:AnimalsCells

  • Flaumenhaft R, Rifkin DB. Cell density dependent effects of TGF-beta demonstrated by a plasminogen activator-based assay for TGF-beta. J Cell Physiol. 1992 Jul; 152(1):48-55. PMID: 1618922.

    Citations: 4   Fields:

    Translation:AnimalsCells

  • Flaumenhaft R, Rifkin DB. Extracellular matrix regulation of growth factor and protease activity. Curr Opin Cell Biol. 1991 Oct; 3(5):817-23. PMID: 1931082.

    Citations: 21   Fields:

    Translation:HumansAnimalsCells

  • Moscatelli D, Flaumenhaft R, Saksela O. Interaction of basic fibroblast growth factor with extracellular matrix and receptors. Ann N Y Acad Sci. 1991; 638:177-81. PMID: 1664684.

    Citations: 1   Fields:

    Translation:AnimalsCells

  • Rifkin DB, Moscatelli D, Flaumenhaft R, Sato Y, Saksela O, Tsuboi R. Mechanisms controlling the extracellular activity of basic fibroblast growth factor and transforming growth factor. Ann N Y Acad Sci. 1991; 614:250-8. PMID: 2024887.

    Citations: 1   Fields:

    Translation:HumansAnimalsCells

  • Rifkin DB, Moscatelli D, Bizik J, Quarto N, Blei F, Dennis P, Flaumenhaft R, Mignatti P. Growth factor control of extracellular proteolysis. Cell Differ Dev. 1990 Dec 02; 32(3):313-8. PMID: 1711916.

    Citations: 15   Fields:

    Translation:AnimalsCells

  • Flaumenhaft R, Moscatelli D, Rifkin DB. Heparin and heparan sulfate increase the radius of diffusion and action of basic fibroblast growth factor. J Cell Biol. 1990 Oct; 111(4):1651-9. PMID: 2170425.

    Citations: 40  

    23 readers on Mendeley

     

    Translation:AnimalsCells

  • Flaumenhaft R, Moscatelli D, Saksela O, Rifkin DB. Role of extracellular matrix in the action of basic fibroblast growth factor: matrix as a source of growth factor for long-term stimulation of plasminogen activator production and DNA synthesis. J Cell Physiol. 1989 Jul; 140(1):75-81. PMID: 2738111.

    Citations: 32   Fields:

    Translation:AnimalsCells

SOURCE

https://connects.catalyst.harvard.edu/profiles/display/Person/27465

https://www.bidmc.org/research/research-by-department/medicine/hemostasis-and-thrombosis/flaumenhaft-lab/research-interests

 

 

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Newly Elect President of Technion, Professor Uri Sivan: Key Contributions to Scientific Innovations

Posted in Intellectual Property, Interviews with Scientific Leaders, Scientist: Career considerations on February 11, 2019| 1 Comment »


Newly Elect President of Technion, Professor Uri Sivan: Key Contributions to Scientific Innovations

 

Reporter: Aviva Lev-Ari, PhD, RN

 

February 7, 2019
By: Office of the Technion Spokesperson

The Technion Council, headed by Mr. Gideon Frank, has elected Professor Uri Sivan of the Faculty of Physics as the next president of Technion. The Council’s decision was based on the recommendation of the Search Committee for the Technion President and received sweeping support from the Academic Assembly. The appointment is subject to the final approval of the International Board of Governors, which is set to convene in June.

Professor Uri Sivan

Prof. Sivan will commence his term as President of Technion on October 1 2019, and will replace the outgoing President Prof. Peretz Lavie, who will complete his term after a decade in office.

Prof. Sivan, 64, a resident of Haifa, is married and the father of three. He served as a pilot in the Israeli Air Force. He has a BSc in Physics and Mathematics, an MSc and PhD in Physics, all with honors from Tel Aviv University.

In 1991, after three years at IBM’s T. J. Watson Research Center in New York, Prof. Sivan joined the Faculty of Physics at Technion.

SOURCE

https://ats.org/news/professor-uri-sivan-elected-new-president-of-the-technion/

 

Key Contributions to Scientific Innovations

  • His research has covered a wide range of fields including quantum mesoscopic physics and the harnessing of molecular and cellular biology for the self-assembly of miniature electronic devices. Prof. Sivan, along with colleagues Profs. Erez Braun and Yoav Eichen, demonstrated for the first time how to harness molecular recognition by DNA molecules for wiring an electric circuit. This study gained considerable resonance and helped pave the way for a new field in nanotechnology using the self-assembly properties of biological molecules to construct miniature engineering systems.
  • His research has focused on the way water orders next to molecules and the effect of this ordering on inter-molecular interactions in biologically relevant solutions. Within this framework, Prof. Sivan’s group designs and builds unique, ultra-high-resolution atomic force microscopes.
  • His research has led to patents and industrial applications. Recently, an Israeli start-up company was established in the field of single cell analysis for cancer diagnostics, based on the technology developed in Prof. Sivan’s lab.
  •  Prof. Sivan is the founding director of the Russell Berrie Nanotechnology Institute (RBNI), which he headed between 2005 and 2010.  RBNI has led the scientific revolution in nanotechnology at Technion and has placed the university at the forefront of global research in the field. RBNI made headlines when Prof. Sivan and Dr. Ohad Zohar engraved the entire Hebrew Bible onto a tiny silicon chip. The Nano Bible was written as part of an educational program developed by the Institute to increase young people’s interest in science and especially in nanotechnology. In 2009, President Shimon Peres presented the Nano Bible to Pope Benedict XVI during his official visit to Israel. Today, there are three copies of the chip worldwide: at the Vatican Library, the Smithsonian Museum in Washington D.C., and the Israel Museum in Jerusalem. The establishment of RBNI spearheaded the development of Israel’s national nanotechnology program, and together with centers established in other Israeli universities, has positioned the country as a world leader in nanotechnology.

APPOINTMENTS

Recently, Prof. Sivan was appointed to head the National Advisory Committee in Quantum Science and Technology of the Council for Higher Education’s Planning and Budgeting Committee (PBC). The committee outlined the national quantum academic program, which was adopted and launched last year.

Prof. Sivan has served as a member of the Israeli National Committee for Research and Development (MOLMOP) and the Scientific Advisory Committee of the Batsheva de Rothschild Foundation. He currently serves on the Advisory Committee of the Maof Fellowships Committee for advancing Arab faculty and is a member of the Israeli Wolfson Foundation Advisory Board.

AWARDS

Prof. Sivan is a renowned lecturer in Israel and abroad. He was awarded with numerous prizes including

  • the Mifal Hapais Landau Prize for the Sciences and Research,
  • the Rothschild Foundation Bruno Prize,
  • the Israel Academy of Sciences Bergmann Prize,
  • the Technion’s Hershel Rich Innovation Award, and
  • the Taub Award for Excellence in Research.

 

SOURCE

https://ats.org/news/professor-uri-sivan-elected-new-president-of-the-technion/

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