Meritorious Awards Accordions

2022 Recipient of the Earl P. Benditt Award

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Joyce E Bischoff, PhD, as the 2022 recipient of the Earl P. Benditt Award, in recognition of her numerous contributions to our understanding of vascular development, the cell biology of hemangioma, and the plasticity of cardiac valve endothelium.  Dr. Bischoff is currently Professor in the Department of Surgery and Member Biological and Biomedical Sciences Graduate Program at Harvard Medical School. She also holds an appointment in the Vascular Biology Program at Boston Children’s Hospital. Dr. Bischoff will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at the 22^nd International Vascular Biology in the San Francisco Bay Area (October 13, 2022).

Dr. Bischoff earned an undergraduate degree in Chemistry at Duke, followed by a PhD in Biochemistry from Washington University, St. Louis, in 1985.  She then pursued postdoctoral research with Harvey Lodish in Cell and Molecular Biology at the Whitehead Institute and joined the faculty of the Department of Surgery at Harvard Medical School in 1990. She rose to the rank of Professor of Surgery in 2010.

Dr. Bischoff is recognized internationally as an expert in the roles played by endothelial cells and pericytes in normal vascular homeostasis and a variety of vascular diseases. For decades, her lab has studied hemangioma, a fast-growing vascular tumor that can causing organ damage, disfigurement and other morbidities. Her lab has used cellular and animal models to identify molecular mechanisms and new therapeutics that safely can prevent hemangiomas from growing to an endangering size. More recently, her lab’s work on vascular neoplasia has extended to poorly-understood capillary, lymphatic, and venous malformations distinct from hemangioma but are also and medical therapies are needed.

In pursuit of cell-based therapies for cardiovascular insufficiency, Dr. Bischoff and colleagues have investigated the utility of endothelial progenitor cell populations for endothelializing vascular grafts in large and small animal models. sheep model and for building networks of human blood vessels rapidly in vivo using athymic nude mice. Their studies have revealed that endothelial colony forming cells can assemble into perfused vessels when injected into ischemic rat myocardium, promoting recovery of heart function over time. Heart valve endothelial cells have also been a focus of Dr. Bischoff’s interest, owing to their unique plasticity compared their counterparts lining large vessels or microvessels.

Dr. Bischoff has published more than 115 peer-reviewed papers and dozens of reviews and served as a Co-Editor -in-Chief of the Springer journal Angiogenesis from 2005-2020. She has received numerous honors and invited lectureships and has served NAVBO both as a Councilor (2005-2008) and as President (2015-2016).

Colleagues writing in support of Dr. Bischoff’s nomination noted that the journal Angiogenesis rose in stature and impact factor under her editorial guidance, and younger colleagues highlighted her generous mentorship and willingness to share the benefit of her experiences as an educator and researcher. “She epitomizes the notion of leading by example while passionately embracing scientific rigor with a uniquely kind and humble touch. She never misses the opportunity to give full credit to her mentees and colleagues, demonstrating how much she values them. Indeed, the greatest testament to Dr. Bischoff's role model in science is the research emanating from her many trainees' independent laboratories.”

Please join us at IVBM2022 at the Oakland Marriott City Center this October to honor Dr. Bischoff as she receives this well-deserved award.

2021 NAVBO EARL P. BENDITT AWARD - GUILLERMO OLIVER, PH.D., NORTHWESTERN UNIVERSITY

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Guillermo Oliver, MS, PhD, as the 2021 recipient of the Earl P. Benditt Award in recognition of his numerous contributions to our understanding of the cell biology of the lymphatic system. Dr. Oliver is currently the Thomas D Spies Professor of Lymphatic Metabolism, the Director of the Center for Vascular and Developmental Biology and Director of the Regenerative Biology & Stem Cell Initiative at Northwestern University. He will present the Benditt Lecture, titled “Prox1 and lymphatics, a personal perspective,” and receive the award, one of NAVBO's highest honors, online on November 2 at 1:00pmET - click here to register.

Dr. Oliver earned an MS (1983) at the Institute of Biomedical Research, National University of Mexico in Cuernavaca, and a PhD (1990) from the School of Sciences, University of Uruguay, Montevideo. His doctoral research, conducted under the mentorship of Edward De Robertis at UCLA, examined the role of homeobox genes in vertebrate pattern formation. Following stints on the faculty of the University of Uruguay and the staff of the Max Planck Institute of Biophysical Chemistry in Gottingen, he joined the faculty at St. Jude Children’s Research Hospital, rising to the rank of Professor in 2006. He moved to the Northwestern Feinberg School of Medicine in 2015, assuming the Spies Professorship and the leadership positions he now holds.

Among the most significant contributions Dr. Oliver has made in his research career is the characterization of the lymphatic system as a fluid-dynamic and developmental marvel, in essence rediscovering a vascular network which had been virtually ignored by researchers during the 20^th century. In a seminal work published in Cell in 1999, his lab identified Prox1 as the first specific marker for lymphatic endothelial cells (LECs) and described the first mouse model devoid of a lymphatic vasculature. Subsequently, his group proposed and demonstrated that blood endothelial cells (BECs) are the default condition from which LEC fate is induced by Prox1 (published in EMBO J, 2002) and that the LEC phenotype is plastic and reversible and requires constant expression of Prox1 to maintain its differentiated state (Genes & Dev, 2008). In 2007, his laboratory demonstrated that most embryonic LECs were venous-derived by using a detailed lineage tracing approach (Genes & Dev, 2007).

Across these years, his laboratory dissected the molecular mechanisms leading to the specification and differentiation of LECs during development. In a surprising twist, Dr. Oliver and his colleagues discovered that a defective lymphatic vasculature promotes obesity in mice (Nat Genetics, 2005). Importantly, in the Discussion section of that paper Dr. Oliver argued that, like Prox1+/− mice, individuals with subtle defects in the patterning and integrity of their lymphatic vasculature might not have overt symptoms of lymphatic dysfunction, and lymphatic abnormalities may therefore remain undetected. This visionary concept is currently becoming valid and relevant, as the functional roles of the lymphatic vasculature in pathophysiological conditions, including obesity, has been increasingly recognized in recent years, changing our conventional views about the roles of the lymphatic vasculature in health and disease. Morphological or functional defects in the lymphatic vasculature have now been uncovered in several pathological conditions supporting his original proposal that subtle, asymptomatic alterations in lymphatic vascular function could underlie the variability seen in the body’s response to a wide range of human diseases. More recently, work in progress in his lab identified an unexpected novel functional role of lymphatic-derived lympho-angiocrine factors in cardiac growth and repair.

Dr. Oliver and his collaborators have published over 120 peer-reviewed papers, and his research on Prox1 in mammalian lymphangiogenesis has earned NIH RO1 support for 18 consecutive years. He enjoys the great respect and admiration of his scientific peers for both his research accomplishments and his role as a mentor for young scientists. Notes of his award nominees: “The creation of the next generation of scientists is arguably the most important contribution a senior scientist can make, and in the case of Dr. Oliver he has populated an entire field of vascular biology. This is a lasting legacy for both Dr. Oliver and vascular biology that is in the true spirit of the Benditt award.”

Please join us on November 2 at 1:00pmET to honor Dr. Oliver as he receives this well-deserved award.

Compiled by William R. Huckle,
NAVBO Editor

2020 NAVBO EARL P. BENDITT AWARD - PATRICIA D'AMORE, SCHEPHEN'S EYE INSTITUTE, MASS EYE AND EAR, HARVARD MEDICAL SCHOOL

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Patricia D’Amore, PhD, MBA, as the 2020 recipient of the Earl P. Benditt Award, in recognition of her numerous contributions to our understanding of vascular development and growth. Dr. D’Amore is currently the Charles L. Schepens Professor of Ophthalmology and Professor of Pathology at Harvard Medical School. She will present the Benditt Lecture"Understanding capillary growth and pathology using the retina as a model system," via an online webinar on November 5 at 1:00pmET.  The webinar will be accessible to all NAVBO members.

Dr. D’Amore earned a PhD in Biology from Boston University in 1977 and pursued postdoctoral research in the Departments of Ophthalmology and Physiological Chemistry at Johns Hopkins, where she was appointed Assistant Professor in 1980. She returned to Boston in 1981 to join Judah Folkman in the Program in Vascular Biology at Boston Children’s Hospital, where she remains a Research Associate in the Department of Surgery. Dr. D’Amore rose to the rank of Associate Professor of Pathology (1989) and Professor of Ophthalmology (1998) at Harvard Medical School, assuming the Schepens Professorship as Director of Research at the Schepens Eye Research Institute of Mass. Eye and Ear in 2012. In 2014, she was appointed Professor of Pathology at Harvard Medical School, where she directs the Howe Laboratory and serves as Associate Chief for Ophthalmology Basic and Translational Research in the Department of Ophthalmology.

Dr. D’Amore is recognized internationally as an expert in vascular growth and development, working at the forefront of angiogenesis research for over three decades. Among her foremost contributions is the identification of vascular endothelial growth factor (VEGF) as the elusive causative factor in ocular diseases characterized by over-exuberant blood vessel growth. These investigations proved fundamental in the rationale for development of anti-VEGF therapies, first approved for clinical use in 2004 and currently in use to treat various cancers, diabetic retinopathy, and age-related macular degeneration. Dr. D’Amore also developed the widely-used hyperoxic murine neonate model of retinopathy, enabling numerous basic scientific investigations of vascular development and preclinical studies of vascular-targeting agents. Her current research focuses on understanding the developmental dynamics and maturational stabilization of the microvasculature.

Dr. D’Amore has published more than 160 peer-reviewed papers, dozens of reviews, and is editor or co-editor of four books. She has received numerous honors, including the Alcon Research Institute Award, the Cogan Award and Proctor Medal from ARVO, the Rous-Whipple Award from the American Society of Investigative Pathology, the Endre A. Balazs Award from the International Society for Eye Research, and the António Champalimaud Vision Award, the highest distinction in ophthalmology and visual science. Most recently, she was elected as a Fellow of American Academy of Arts & Sciences, Medical Sciences.

Colleagues writing in support of Dr. D’Amore’s nomination noted that “…D’Amore is an outstanding teacher, mentor and communicator in the world of vascular biology, locally, nationally and internationally. She is a much sought-after collaborator and colleague, who is passionately committed to the academic mission and presents a wonderful role model for young women trainees in the biomedical sciences. She thus embodies the spirit of Dr. Earl Benditt, as he is remembered for both his scientific contributions and his mentorship.”

Please join Michael Gimbrone online November 5 to honor Dr. D’Amore as she receives this well-deserved award.

Compiled by William R. Huckle,
NAVBO Editor

2019 NAVBO EARL P. BENDITT AWARD - WILLIAM C. SESSA, YALE SCHOOL OF MEDICINE

The NAVBO Meritorious Awards Committee and Council is pleased to announce the selection of William Sessa, PhD, as the 2019 recipient of the Earl P. Benditt Award, in recognition of his numerous contributions to our understanding of mechanisms regulating nitric oxide production in the vascular endothelium. Dr. Sessa is currently the Alfred Gilman Professor of Pharmacology and Professor of Medicine at Yale University, where he also serves as Vice Chairman of Pharmacology and Director of the Vascular Biology & Therapeutics Program. He will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at Vascular Biology 2019 in Pacific Grove, California (October 27, 2019).

Following undergraduate studies at the Philadelphia College of Pharmacy and Sciences, Dr. Sessa completed M.S. and Ph.D. studies in Pharmacology at the University of Rhode Island and New York Medical College. He conducted post-doctoral research at the William Harvey Research Institute in London and the University of Virginia, after which he joined the faculty of Yale’s School of Medicine, rising to the rank of Professor of Pharmacology in 1999. His scholarly contributions, reported in well over 300 peer-reviewed publications, book chapters, and reviews, have earned Dr. Sessa numerous awards and honors in the U.S. and internationally, including the 2000 John Jacob Abel Medal in Pharmacology from American Society of Pharmacology and Experimental Therapeutics and the 2010 William Harvey Medal. In 2017, he was awarded an Outstanding Investigator Award (R35) from NHLBI, in strong support of his ongoing investigations of endothelial function.

As noted in his bio, Dr. Sessa’s principal contributions to science revolve around the molecular aspects of endothelial nitric oxide synthase activation and how eNOS regulates angiogenesis, vascular permeability, atherosclerosis and vascular remodeling. As a post-doctoral fellow at UVa, his was one of the three labs to clone eNOS. Across his career as a faculty member, his lab has probed eNOS subcellular trafficking, post-translational lipidation, characterized major sites of eNOS phosphorylation, and showed that growth factors and shear stress regulate eNOS protein-protein interactions and NO release from the endothelium. He was the first to demonstrate that eNOS derived NO regulates angiogenic behaviors of endothelial cells in an autocrine manner in response to VEGF, and it is now appreciated that NO contributes to several of the biological actions of VEGF. Although eNOS was considered a “constitutive gene,” his lab demonstrated that eNOS mRNA and protein levels were induced by exercise training, consistent with a critical adaptive response to changes in shear, pressure and flow.

Dr. Sessa has served his institution and profession in a number of capacities, chairing study sections at the NIH and American Heart Association and serving as President of NAVBO and editor for major cardiovascular journals. As a research mentor, he has trained dozens of post-doctoral fellows and doctoral students, the latter group including NAVBO’s 2017 Judah Folkman Awardee, Guillermo García-Cardeña, PhD and the 2011 Springer Junior Investigator Awardee, Carlos Fernández-Hernando, PhD. Please join us for VB2019 at Asilomar this October to honor Dr. Sessa as he receives this well-deserved award.

Dr. Sessa will give his talk entitled, "Integration of endothelial function and lipid metabolism," on Sunday, October 27, 2019 at 8:15pm in Merrill Hall at the Asilomar Conference Grounds.

Compiled by William R. Huckle,
NAVBO Editor

2018 NAVBO EARL P. BENDITT AWARD - RAKESH JAIN, MASSACHUSETTS GENERAL HOSPITAL, HARVARD MEDICAL SCHOOL

The NAVBO Meritorious Awards Committee and Council is pleased to announce the selection of Rakesh K. Jain, Ph.D., as the 2018 recipient of the Earl P. Benditt Award, in recognition of his numerous contributions to our understanding of the unique characteristics of tumor vasculature. Dr. Jain is currently the Andrew Werk Cook Professor of Tumor Biology (Radiation Oncology) at Harvard Medical School and Director of the Edwin L. Steele Laboratory for Tumor Biology at Massachusetts General Hospital. He will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at Vascular Biology 2018 in Newport, Rhode Island (October 17, 2018).

Following undergraduate studies in Chemical Engineering at the Indian Institute of Technology in Kanpur, Dr. Jain received his M.S. and Ph.D. in Chemical Engineering from the University of Delaware. He held faculty positions in Chemical and Biomedical Engineering at Columbia University and Carnegie Mellon University prior to joining the Harvard faculty in 1991. He has served on a multitude of editorial boards, review panels, and advisory groups. Dr. Jain’s research has been supported steadily for decades by the NIH and other agencies, including the Gates Foundation and Department of Defense. His scholarly contributions, reported in well over 650 publications, book chapters, and reviews, have earned Dr. Jain scores of awards and honors in the U.S. and internationally, including election to the United States National Academies of Medicine (2003), Engineering (2004), and Sciences (2009). He holds seven U.S. patents and received the United States National Medal of Science for 2013.

Dr. Jain is regarded as a trailblazer in the study of tumor microenvironment, examining in detail the notion that the relationships between tumors and their surrounding non-tumor tissue—including blood vessels—are essential determinants of disease progression, therapeutic efficacy, and patient prognosis. Dr. Jain’s nominators note that, in sum, his work has provided “…unprecedented molecular, cellular, anatomical and functional insights into the vascular pathophysiology of tumors, for proposing the seminal hypothesis that antiangiogenic therapy can ‘normalize’ the aberrant vasculature and microenvironment of tumors and thereby improve both delivery and efficacy of treatment of solid tumors.” His studies revealed that the blood and lymphatic vasculature, fibroblasts, immune cells and the extracellular matrix associated with tumors are abnormal, collectively creating a hostile tumor microenvironment characterized by hypoxia, low pH and high interstitial fluid pressure. He and his collaborators subsequently hypothesized that normalizing the microenvironment may improve treatment outcome and subsequently have demonstrated that judicious use of antiangiogenic agents—originally designed to starve tumors—could transiently “normalize” tumor vasculature, alleviate hypoxia, increase delivery of drugs and anti-tumor immune cells, and improve the outcome of various therapies, including immunotherapy. Dr. Jain’s more recent work includes efforts to improve the vascular competence of engineered tissue in the context of regenerative medicine. By generating endothelial and smooth muscle cells from human embryonic stem cells and induced pluripotent stem cells, his lab is bringing functional and durable engineered vessels closer to translation into the clinic.

Please join us for VB2018 in Newport this October to honor Dr. Jain as he receives this well-deserved award.  Dr. Jain will give his talk, "Reengineering the tumor microenvironment to improve cancer treatment: Bench to bedside" on October 17, 2018 at 3:15pm in the Grand Ballroom of Gurney's Newport Resort and Marina.

Compiled by William R. Huckle,
NAVBO Editor

2017 NAVBO EARL P. BENDITT AWARD - PETER LIBBY, BRIGHAM & WOMEN'S HOSPITAL, HARVARD MEDICAL SCHOOL

BRIGHAM AND WOMEN'S HOSPITAL CHIEF OF CARDIOVASCULAR MEDICINE AND HARVARD PROFESSOR OF MEDICINE PETER LIBBY, MD

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Peter Libby, M.D., as the 2017 recipient of the Earl P. Benditt Award, in recognition of his numerous significant contributions to elucidating the pathogenesis of atherosclerosis and its complications. Dr. Libby is currently Mallinckrodt Professor of Medicine, Harvard Medical School, serving also as Senior Physician at Brigham and Women’s Hospital and Consulting Physician in the Department of Medical Oncology at the Dana-Farber Cancer Institute. He will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at Vascular Biology 2017 in Pacific Grove, California (October 15-19, 2017).

Following undergraduate studies in Biochemistry at the University of California-Berkeley, Dr. Libby received his M.D. from UC-San Diego in 1973 and trained thereafter as an intern, resident and fellow at Peter Bent Brigham Hospital and Harvard Medical School. He has held a series of research and clinical positions at Harvard and Tufts University, rising to the rank of Professor of Medicine at Harvard in 1996. He has held leadership positions in numerous clinical trials and served on a multitude of editorial boards, review panels, and advisory groups. Dr. Libby’s research has been supported steadily by the NIH and other agencies for decades, and he serves as the PI of a T32 training grant in cardiovascular research that is in its 32nd year of funding. His scholarly contributions, reported in well more than 350 peer-reviewed publications and over 400 book chapters and reviews, have earned Dr. Libby dozens of honors in the U.S. and internationally, including a MERIT Award from the National Heart, Lung, and Blood Institute (1993-2003), the American Heart Association’s Basic Research Prize, (2011), and a Lifetime Achievement Award from the Heart Failure Association of the European Society of Cardiology (2014).

As a basic scientist, Dr. Libby has achieved worldwide recognition for his laboratory’s important work on the biology of the endothelium, vascular smooth muscle, and their interactions with inflammatory cells. Of particular note is his contribution to our understanding of the roles of CD40 and CD40L, matrix metalloproteinases and soluble inflammatory mediators. Those writing in support of Dr. Libby’s nomination for the Benditt Award laud his willingness to critically evaluate mouse models as predictors of human pathophysiology or fruitful therapeutic approaches. Dr. Libby and his colleagues were the first to discover that vascular wall cells produce pro-inflammatory cytokines and that inflammatory mechanisms change collagen metabolism and control the susceptibility of atheromata to disrupt and cause thrombosis – key elements of our current understanding of the progression of atherosclerotic disease.

Dr. Libby enjoys a stellar reputation as a teacher and mentor and is a highly sought-after speaker both nationally and abroad. His service to NAVBO likewise has been exemplary: as a “founding member,” he has played leadership roles on the Steering and Development Committees, on Council (1994-1996, 2012-2015), and has fostered productive relationships between NAVBO and other organizations with common goals and constituencies, particularly the American Heart Association.

Please join us at Vascular Biology 2017 at the Asilomar Conference Grounds this fall to honor Dr. Libby as he receives this well-deserved award.  Dr. Libby will give his talk, "Inflammation in Cardiovascular Disease: A Translational Journey" on October 18, 2017 at 3:15pm in Merrill Hall.

Compiled by William R. Huckle,
NAVBO Editor

2016 NAVBO EARL P. BENDITT AWARD - ELISABETTA DEJANA, UNIVERSITY OF UPPSALA

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Elisabetta Dejana, Ph.D.,
as the 2016 recipient of the Earl P. Benditt Award, in recognition of her pioneering studies in endothelial cell biology and inflammation.  Dr. Dejana is currently Chief of the Angiogenesis Program, Institute of Molecular Oncology, Italian Foundation for Cancer Research (FIRC) in Milan, Italy and professor of Pathology at the Department of Immunology, genetics and Patology, University of Uppsala, Uppsala, Sweden.  She will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at the 19th International Vascular Biology Meeting (October 30-November 3, 2016) in Boston, Massachusetts.

Dr. Dejana received her doctorate in Biological Sciences from the University of Bologna and has held a variety of research and academic posts in Paris, Grenoble, Stockholm, and Milan. She became Chief of the Angiogenesis Program at FIRC in 2000 and was appointed Full Professor of General Pathology in the School of Sciences at the University of Milan in 2002. She has participated on numerous scientific advisory boards, and her research contributions, reported in more than 300 scientific publications, have earned Dr. Dejana awards across Europe and in the US.

Dr. Dejana has achieved international recognition for elucidation of molecular mechanisms by which cells of the vascular endothelium interact with each other, with cells of the immune system, and with the extracellular matrix. These relationships are fundamental to any physiological process involving dynamics of blood vessel structure, including modulation of vascular permeability, angiogenesis or vascular regression, and well-regulated inflammation and hemostasis. These processes are of particular importance in cardiovascular diseases that involve pathologies of immune function, vascular leakage, hemorrhage and thrombosis.

A major contribution from Dr. Dejana’s laboratory has been characterization of the molecular architecture of endothelial cell-cell junctions. Her seminal 1992 paper in the Journal of Cell Biology reported the discovery of VE-cadherin as a key protein component of cell-to-cell adherence junctions. Subsequent research has revealed that formation of VE-cadherin/Β-catenin complexes not only shapes endothelial junctions but also allows transfer of intracellular signals that mediate such important functions such as endothelial tubulogenesis, establishment of polarity, contact inhibition of cell proliferation and inhibition of apoptosis. The impact of these findings throughout the international vascular biology community is evidenced by the appearance of >2100 publications related to VE-cadherin in peer-reviewed journals. In addition to VE-cadherin, Dr. Dejana identified the first member of the junctional adhesion molecule family (JAM-A), a small immunoglobulin-like molecule enriched at endothelial and epithelial cell-to-cell tight junctions. Her lab has found, using approaches of targeted gene modulation and blocking monoclonal antibodies, that JAM-A has a fundamental role in regulating leukocyte and tumor cell transmigration through endothelial cell-to-cell junctions.

More recently, Dr. Dejana’s research has explored the role of defective adherens junction components in Cerebral Cavernous Malformations (CCMs), lesions of the cerebral vasculature that can lead to hemorrhagic stroke and seizure disorders. The architecture of endothelial cell-cell junctions is markedly altered in this disease, producing the vessels that are fragile and with incomplete polarization and poorly formed lumina. The defective junctional components CCM1, -2, and -3 described by Dr. Dejana represent novel biochemical targets underlying this family of disorders, and her experimental systems that model the features of CCMs provide a valuable setting in which testing potential therapeutic compounds.

Please join us at IVBM in Boston this fall to honor Dr. Dejana as she receives this well-deserved award.  Dr. Dejana will give her talk, "Transcriptional Regulation of Endothelial Cell Plasticity in Health and Disease" on November 3, 2016 at the International Vascular Biology Meeting in Boston, MA.

Compiled by William R. Huckle,
NAVBO Editor

2015 NAVBO EARL P. BENDITT AWARD - ELI KESHET, HADASSAH MEDICAL SCHOOL, THE HEBREW UNIVERSITY

Dr. Keshet will give his talk, "VEGF, Blood Vessels and Stem Cell Niches" on October 21, 2015 at Vascular Biology 2015 in Hyannis, MA on Cape Cod.

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Eli Keshet, M.Sc., Ph.D., as the 2015 recipient of the Earl P. Benditt Award, in recognition of his pioneering studies on the regulation of angiogenesis. Dr. Keshet is currently Full Professor in Developmental Biology and Cancer Research at the School of Medicine of the Hebrew University of Jerusalem, Israel. He will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at Vascular Biology 2015 in Hyannis, Massachusetts, on October 21, 2015.

Dr. Keshet received his B.Sc., M.Sc., and Ph.D. degrees from the Hebrew University. His post-doctoral work included studies in the laboratory of Howard Temin at the University of Wisconsin (1976-79), followed by stints as Senior Scientist and Senior Lecturer at the Weizmann Institute and Hebrew University, respectively. After two years as a Visiting Scientist at the NIH, Dr. Keshet joined the faculty at Hebrew University in 1986, rising to the rank of Full Professor in 1993.

The contributions of Dr. Keshet's research group on Vascular Endothelial Growth Factor (VEGF) can be found throughout the field of vascular biology. Their seminal paper in Nature in 1992 identified hypoxia as key regulator of VEGF expression, only a few short years after the biochemical definition of this key angiogenic agent. Thus, a link was established between the tissue microenvironment and the molecular induction of angiogenesis. As the starting point of molecular hypoxia research, this work led to exploration of hypoxia-inducible factors (HIFs) and prolyl hydroxylases as regulators of gene expression by ischemia. Subsequently, Dr. Keshet identified hormonal regulators of VEGF expression and characterized VEGF as a survival factor for the developing vasculature. His laboratory experimentally modeled retinopathy of prematurity, describing the "front" of invading endothelial cells now conceptualized as the tip cell – stalk cell relationship. His work demonstrating that VEGF withdrawal leads to ablation of immature blood vessels helped establish VEGF as a meaningful target for translational anti-angiogenesis research. More than twenty years into his academic career, Dr. Keshet continues to identify avenues of VEGF research, including identifying a novel splice variant of sVEGFR1 associated with human preeclampsia. More recently, the Keshet lab has described perfusion-independent control of the stereotypic branching of lung airways by blood vessels during development.

Beyond these landmark contributions to our knowledge of vascular biology, Dr. Keshet's nomination for the Benditt Award noted that he is "...a role model... as a person and as a scientist... truly one of the most creative scientists... modest and humble..." "More importantly, his lab is proof of the fact that what counts in science is brains and not manpower or technological power." Please join us at Hyannis in October to honor Dr. Eli Keshet as he receives this well-deserved award.

Compiled by William R. Huckle,
NAVBO Editor

2014 NAVBO EARL P. BENDITT AWARD - JORDAN S. POBER, YALE UNIVERSITY SCHOOL OF MEDICINE

Dr. Pober will give his talk, "Lymphocyte Interactions with the Vessel Wall" on October 22, 2014 at Vascular Biology 2014 in Pacific Grove, CA (Monterey Peninsula).

The NAVBO Meritorious Awards Committee and Council is pleased to announce the selection of Jordan S. Pober, M.D., Ph.D, as the 2014 recipient of the Earl P. Benditt Award, in recognition of his pioneering work in endothelial cell biology and vascular immunology. Dr. Pober is currently the inaugural Bayer Professor of Translational Medicine, Director of Human and Translational Immunology Program, and Vice-Chair of the Department of Immunobiology for the Section of Human and Translational Immunology at the Yale University School of Medicine. Dr. Pober will present the Benditt Lecture and receive the award, one of NAVBO's highest honors, at Vascular Biology 2014 in Pacific Grove, California, on October 22, 2014.

Dr. Pober received his M.D. and Ph.D. in 1977 from Yale, having performed graduate research under the direction of Lubert Stryer and Jack Strominger, themselves major figures in biochemistry and immunology, respectively. Dr. Pober has remained a leader in the vascular biology field for over 30 years. His important work in the early 1980s demonstrated that cytokines of innate immunity (TNF and IL-1) and of adaptive immunity (IFN-gamma and IL-4) act on human endothelium to induce molecules that mediate interactions with circulating leukocytes including Class I and, unexpectedly, Class II MHC molecules, leukocyte adhesion molecules and chemokines. Based upon these discoveries, Dr. Pober formulated and introduced the concept of endothelial activation. This concept is now a widely accepted paradigm of inflammation, changing our view of the endothelium from a passive barrier to a central and active player in inflammatory processes. In this respect, Dr. Pober's work clearly reaches the ideal of the Benditt Award as recognizing "...an individual who has made an outstanding discovery or developed a concept that has been seminal to our understanding of vascular biology or pathology."

In addition to his influential work in vascular inflammation, Jordan laboratory was one of the first to clone a molecule (PDGF B) from endothelial cells, isolate Weibel-Palade bodies, and define mechanisms of secretion of vonWillebrand Factor. More recently, he has continued to advance important concepts in vascular immunobiology as evidenced by his work on the immunologic causation of graft vasculopathy by cytokines such as IFN-gamma and the generation of synthetic microvessels as a means to improve blood flow. He also continues to make new and interesting observations on how vascular cells may regulate adaptive immune responses through antigen presentation.

In addition to his scholarship, Jordan was both a founding member and former President of NAVBO (1997-1998) and has served the scientific community on numerous editorial boards and study sections. He founded the first interdepartmental program at Yale Medical School in 1991 and has assembled one of the preeminent vascular biology programs in the country. In 2007, he initiated the Human Translational Immunology Program and has continued to recruit and build this important program at Yale to apply the discoveries of immunology to immune modulated diseases in humans such as transplant arteriopathy, diabetes and cancer. Jordan is widely regarded as an outstanding mentor, incredible intellect and invaluable colleague. Please join us at Asilomar to honor Jordan as he receives this well-deserved award in October.

Compiled by William R. Huckle,
NAVBO Editor

2013 NAVBO EARL P. BENDITT AWARD - MICHAEL KLAGSBRUN, HARVARD MEDICAL SCHOOL

Dr. Klagsbrun gave his talk, "FromFGF to neuropilin: Identifying novel regulators of angiogenesis and cancer" via a pre-recorded video. Dr. Patricia D'Amore was on hand at the meeting to accept the award on his behalf.

The NAVBO Meritorious Awards Committee and Council are pleased to announce the selection of Michael Klagsbrun, Ph.D., as the 2013 recipient of the Earl P. Benditt Award, in recognition of his long history of accomplishment in elucidating the role of growth factors in vascular homeostasis and disease. Dr. Klagsbrun will present the Benditt Lecture, "FromFGF to neuropilin: Identifying novel regulators of angiogenesis and cancer," and receive the award, one of NAVBO's highest accolades, at the NAVBO Workshops in Vascular Biology 2013 (October 20-24) in Hyannis, Massachusetts.

Dr. Klagsbrun earned his Ph.D. from the University of Wisconsin-Madison in the laboratory of Robert Bock and pursued post-doctoral training in the Laboratory of Biochemical Pharmacology, in what was then the NIH's Institute of Arthritis, Metabolism, and Digestive Diseases. Following a stint as a staff member at the NIH, he joined the Department of Surgery at Harvard Medical School in 1973 and has remained at that institution ever since, earning the position of Patricia K. Donahoe Professor of Surgery in 2001. Dr. Klagsbrun is currently Senior Associate in Medicine, Vascular Biology Program at Boston Children's Hospital.

Dr. Klagsbrun's laboratory is credited with the first purifications of basic fibroblast growth factor (FGF-2), a potent angiogenic factor, and of heparin-binding EGF-like growth factor (HB-EGF), a potent smooth muscle mitogen. Dr. Klagsbrun's colleagues point to his introduction of heparin-affinity chromatography to the purification of growth factors as a significant accelerator of research into the regulation of cell proliferation in general, and of vascular endothelial mitogenesis in particular.

More recently, the Klagsbrun lab has purified and characterized the neuropilin class of vascular growth
factor receptors that act as novel receptors for members of the VEGF family of angiogenic factor. Neuropilin was originally described as a receptor for semaphorin, a protein involved in regulating axon guidance. These studies have suggested that similar molecular mechanisms regulate angiogenesis and neuronal guidance, both of which are networking processes whose close regulation is essential during prenatal development. This work, published in Cell, yielded landmark findings that have transformed our view of the role of neuropilin in regulating key biological processes. Since that original study, Dr. Klagsbrun and his group have gone on to demonstrate that VEGF binds both neuropilin and VEGFR-2 to form a ternary complex that enhances VEGF's angiogenic activity. His work with neuropilin knockouts in mice and knockdowns in zebrafish was the first to demonstrate the neuropilins are necessary for angiogenesis. These studies have led to the discovery that members of the class-3 semaphorin family of axon guidance mediators actually inhibit angiogenesis.

In the realm of the EGF receptor family of proteins, Dr. Klagsbrun and his group have found that tumor endothelial cells, unlike normal endothelial cells, express ERbB1 and that EGFR KI inhibits tumor growth partly by blocking tumor endothelial EGFR activity. These studies suggest that it may, in fact, be possible to target tumor blood vessels without affecting the normal vasculature, a finding with significant therapeutic importance.

To quote from a letter of nomination: "It is my opinion that the field of vascular biology would be ten years behind its present accomplishments had it not been for the pioneering and continuing work of Dr. Michael Klagsbrun. ... with nearly 300 publications, many in the very best journals, and the clear credit for developing several new areas within the field of vascular biology, Dr. Klagsbrun's accomplishments should not be underestimated. He is a true pioneer, a creative thinker, a rigorous scientist and one of the great lights of our field."

Compiled by William R. Huckle,
NAVBO Editor

2012 NAVBO EARL P. BENDITT AWARD - BRADFORD C. BERK, UNIVERSITY OF ROCHESTER MEDICAL CENTER

Dr. Berk holds the 2012 jade crystal Earl P. Benditt Award just after giving his talk, "How Many Dynes Make a Good Time?" at the NAVBO Workshops in Vascular Biology 2012 in Monterey, CA

The Earl Benditt Award was presented to Bradford C. Berk, M.D., PhD. at the NAVBO Workshop in Vascular Biology in Asilomar. This award recognized the many contributions that Dr. Berk has made to vascular biology over the duration of his career. His cleverly entitled presentation "How Many Dynes Make a Good Time" integrated his many avenues of investigation. He began his presentation with "Hemodynamics 101", summarizing many years of research by engineers, vascular biologists and physiologists, who have described the roles of shear stress, disturbed blood flow, and the predilection for atherosclerosis to occur at sites of disturbed flow. One of the most intriguing mysteries of mechano transduction is what are the shear stress receptors, and how do they transmit physical forces into biological responses.

A critical atheroprotective biomechanical pathway identified by the Berk laboratory was the MEK5-ERK5 signal transduction cascade in endothelial cells. Steady flow stimulates all of the MAP kinases with the exception of JNK. The Berk lab and many others showed activation of an atheroprotective pathway that involves MEK5- ERK5-PPARg and KLF2 signaling. Steady flow activates both anti-inflammatory and pro-survival pathways, and inhibits pro-inflammatory and death pathways such as those stimulated by TNF. Specifically, the laboratory of Dr. Wang Min and Berk showed that steady flow inhibited Apoptosis Signal Regulated Kinase (ASK1). ASK1 is activated by reactive oxygen species, as well as by TNFa, and leads to apoptosis, endothelial cell dysfunction, and inflammation. Steady flow inhibits ASK1 activation by enhanced interaction of ASK1 with its inhibitor, thioredoxin.

Because there was no change in the amount of thioredoxin, and increase in its activity Dr. Berk's laboratory hypothesized that steady flow decreased a thioredoxin inhibitory protein. This lead to the identification of thioredoxin interacting protein (TXNIP) by down regulating TXNIP under conditions of steady flow. In contrast, disturbed flow increases TXNIP expression. In TXNIP deficient mice, the up regulation of VCAM-1 by TNFa was reduced. Furthermore, endothelial TXNIP expression was increased in areas of disturbed flow (e.g. branch points) in vivo, and increased in vitro by disturbed flow. This increase in TXNIP is also required for leukocyte adhesion. KLF2 reverses TXNIP-induced leukocyte adhesion molecule expression (ICAM, VCAM) and interestingly, disturbed flow inhibits KLF2 promoter activity.

ERK5 also inhibits TNF induced JNK activation, and inhibition of this kinase by an inhibitor (BIX02188) prevents flow inhibition of TNF. Further exploration of the mechanism of ERK5 inhibition lead to the identification of a role for protein kinase C z (PKCz). PKCz is activated by disturbed flow; Berk's laboratory showed that TNF cleaved PKCz generating a catalytically active form, CAT z via activation of caspase 3; and flow inhibited this cleavage as well as caspase-3 activation, thus interrupting a positive feedback loop induced by TNF that would otherwise lead to endothelial apoptosis. PKCz crosstalk with the ERK5-KLF2 pathway thus modulates vascular inflammation. In addition to promoting leukocyte binding to endothelial cells via induction of ICAM, this kinase stimulates endothelial apoptosis via JNK and caspase 3 activation, as well as by stimulating p53 SUMOylation.

Thus flow can stimulate both atheroprotective (MEK5-ERK5-KLF2) and atheropromoting (PKCz-JNK). More recently the laboratories of Abe and Berk have shown that disturbed flow stimulates inflammation and endothelial apoptosis by promoting phosphyloration of ERK5 by PKCz, thereby inhibiting activation of KLF2. Furthermore, TXNIP inhibits KLF2 transcription by acting as a co-repressor of KLF2 gene transcription. Elucidation of the counter-regulatory pathways explains the site specific nature of atherosclerosis, with steady flow promoting anti-inflammatory, vasodilatory and pro-survival signals. In contrast, disturbed flow stimulates pro-inflammatory, vasoconstrictor and pro-death responses.

Dr. Berk acknowledged his many students, post-doctoral fellows, assistants and collaborators who contributed to the work that he presented: Jun-ichi Abe, Keigi Fujiwara, Gwen Garin, Ryan Hoefen, Zheng-Gen Jin, Geun-Young Kim, Rich Lee, Wang Min, Patrizia Nigro, Xinchun Pi, Oded Spindel, James Surapisitchat, Xiaoquin Wang, Chang-Hoon Woo, Cameron World, Hide Yamawaki and Chen Yan.

by Mary Gerritsen