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The Endocrine Society |
Citation for the 2006 Fred Conrad Koch Award of The Endocrine Society to Dr. Gerald M. Reaven
The 2006 Fred Conrad Koch Award of The Endocrine Society is bestowed upon Gerald M. Reaven, M.D., Professor of Medicine at Stanford University, in recognition of his exceptional contributions to endocrinology and metabolism and development of the concepts of the metabolic syndrome.
Dr. Reaven received his undergraduate and medical education at the University of Chicago and, after residency at the University of Michigan, went to Stanford as a research fellow. He subsequently joined the faculty where he rose to Professor of Medicine and Head of the Division of Endocrinology and Metabolic Diseases, as well as Director of the General Clinical Research Center, Head of Gerontology and Director of Geriatric Research.
Dr. Reaven’s interest in diabetes and metabolism and their relationship to cardiovascular disease dates back almost 45 years, when he first noted an association between carbohydrate intolerance, hyperlipidemia, and myocardial infarction, even in patients without known diabetes mellitus. Over many years of productive clinical and basic research, Dr. Reaven has approached this and other questions from multiple directions. He has studied the role of amino acids and sulfonylureas in stimulating insulin secretion; the kinetics of triglyceride turnover and VLDL turnover in humans and rodents; the role of insulin in endogenous hypertriglyceridemia; the role of lipoprotein lipase in hypertriglyceridemia; the role of diet, renal function, and insulin in control of triglycerides and the relationship between these parameters and insulin receptor binding; as well as response to various antidiabetic and antihyperlipidemic drugs. He has developed new and simplified approaches to assessing complex metabolic parameters, including the measurement of steady-state plasma glucose, to assess insulin sensitivity in normal and diabetic subjects in large population studies. Using this approach, he has defined the normal range of variation in insulin sensitivity in healthy individuals with normal glucose tolerance, as well as the relationship between insulin sensitivity and plasma-free fatty acid concentration, endogenous glucose production, and fasting hyperglycemia in normal and type 2 diabetic individuals.
In an elegant series of animal and human studies, Reaven defined the effect of differences in the amount and kind of dietary carbohydrate on plasma glucose and insulin responses, the fructose-induced model of insulin resistance, and the relationship between insulin resistance and plasma triglyceride and VLDL turnover in man. He demonstrated the close relationship between insulin secretion and insulin action in nonobese and obese individuals with and without type 2 diabetes mellitus and characterized the effect of plasma glucose on glucose utilization and metabolic clearance rate, as well as the effects of antidiabetic drugs on various aspects of glucose, insulin, and lipid metabolism in patients with diabetes mellitus.
Certainly, Dr. Reaven’s most important contribution has been the insight he has provided to defining and understanding syndrome X, the syndrome that links insulin resistance, hypertension, dyslipidemia, and varying degrees of normal to abnormal glucose tolerance with risk for coronary artery disease. This syndrome is known to affect between 45 and 60 million Americans, including over one third of people over age 60 and now almost 15% of children and teens. It thus constitutes the most wide-reaching endocrine/metabolic public health problem.
As a result of this work, Dr. Reaven has been recognized by the Banting Award for Distinguished Scientific Achievement of the American Diabetes Association, the Banting Memorial Lectureship of the British Diabetes Association, the Joslin Memorial Lecture of the Massachusetts American Diabetes Association, Nordisk-McGill Lecturer at the University of Montreal, the Claude Bernard Lectureship of the European Association for the Study of Diabetes, the Novartis Award for Long-Standing Achievement in Diabetes, the Linus Pauling Functional Medicine Award and the Frontiers in Science Award, and the American Association of Clinical Endocrinologists. He has served on the Editorial Boards of Endocrinology, Diabetologia, American Journal of Physiology: Endocrinology & Metabolism, Hormone and Metabolic Research, Diabetic Medicine, Journal of Internal Medicine, Diabetes/Metabolism Reviews, and The Journal of Clinical Endocrinology & Metabolism and as Editor-in-Chief of the Journal of Gerontology. He also served as a member and then chairman of the National Diabetes Advisory Board of the National Institutes of Health. Dr. Reaven has also received the Renold Medal of the American Diabetes Association in recognition of his distinguished service in the training of students, fellows, and other research scientists.
In summary, Dr. Reaven is truly an outstanding physician-scientist who has made exceptional contributions to endocrinology and metabolism, to our understanding of human disease, and to training of future scientists. He is most worthy of recognition of the Fred Conrad Koch Award of The Endocrine Society.
C. Ronald Kahn
Citation for the 2006 Ernst Oppenheimer Award of The Endocrine Society to Dr. Charis Eng
Charis Eng, M.D., Ph.D., is a gifted endocrine investigator whose pioneering contributions and leadership have been critical to the rapid advancement of the interface between basic genetics and genomics research and clinical practice, especially in the field of endocrine neoplasia. The clinical implications of her work are that gene-based testing can result in earlier diagnosis that can prevent disease, treat it more effectively, and define appropriate organ-specific surveillance and prophylaxis.
Dr. Bruce Ponder introduced Dr. Eng to the world of endocrine research when she was a postdoctoral fellow in his lab at the University of Cambridge, where she also trained formally in the practice of clinical cancer genetics (1992–1995). In her characteristic manner, Dr. Eng plunged tirelessly into this project and, within a few months of her arrival, the RET proto-oncogene was identified as the MEN2A susceptibility gene; her finding was published in Nature in June of 1993. She subsequently went on to identify a single germline mutation in RET that predisposes to MEN 2B, making this an absolute molecular diagnostic test.
As an independent investigator, Dr. Eng, together with Dr. Lois Mulligan, led a multinational group that obtained definitive data on the specific risks of developing the neoplastic conditions that comprise MEN 2: medullary thyroid cancer, pheochromocytoma, and parathyroid hyperplasia. Her delineation of specific genotype-phenotype associations has led to use of genetic testing for molecular diagnosis, clinical prediction, and surveillance recommendations. Her work continues to define the optimal approach to management of individuals in affected kindreds and serves as a model for the practice of clinical cancer genetics.
Extending her key description of RET genotype-phenotype correlation in MEN 2, Dr. Eng and her collaborator of 12 years, Dr. Hartmut Neumann, demonstrated that a remarkable 25% of apparently sporadic pheochromocytomas carry germline mutations in one of four genes. In a series of papers published in The New England Journal of Medicine and JAMA, the multinational team led by Eng and Neumann showed that specific clinical features are associated with mutations in specific genes, thus enabling the clinician to prioritize which gene to begin testing.
Dr. Eng was the first to identify germline mutations in PTEN as the cause of Cowden syndrome, an under-diagnosed inherited follicular thyroid neoplasia syndrome, and related disorders. Her meticulous phenotyping has led to the discovery that subsets of several other disparate syndromes are also due to germline PTEN mutations. She proposed that, instead of clinical syndrome name, the subsets of these disorders associated with PTEN mutations should be classified by gene, i.e. the PTEN Hamartoma Tumor Syndrome. This work has resulted in a key role for molecular-based diagnosis and surveillance recommendations in the management of these clinically puzzling disorders and has been codified in national practice guidelines. Remarkably, she has extended her PTEN work to basic signal transduction and cell biology. Dr. Eng was the first to show that this cytoplasmic phosphatase actually traverses into the nucleus. She showed that, via two overlapping nuclear localization signal-like sequences, PTEN interacts with major vault protein to enter the nucleus, peaking during the G0–G1 phase of the cell cycle. She went on to show that nuclear-PTEN was associated with G1 cell cycle arrest, whereas cytoplasmic PTEN was associated with apoptosis. These observations have defined a nontraditional means of PTEN inactivation that will serve as a novel target of prevention and treatment for many sporadic cancers.
Dr. Eng has received multiple previous honors, including election to membership in the American Society for Clinical Investigation in 2001, when she was one of three new inductees, from among 61, to be selected to present a plenary session at her inaugural meeting. Dr. Eng is the recipient of a Doris Duke Distinguished Clinical Scientist Award (2002). She has been elected a Fellow of American Association for the Advancement of Science (2003) and the Association of American Physicians (AAP, 2004). Dr. Eng was recently the 2005 recipient of the American Thyroid Association’s prestigious Van Meter Award.
Dr. Eng currently serves as the founding director of the Genomic Medicine Institute at the Cleveland Clinic Foundation and Professor and Vice Chair of the Department of Genetics at Case Western Reserve University School of Medicine. She is senior editor of Cancer Research, an associate editor of The Journal of Clinical Endocrinology & Metabolism, and serves on the Board of Directors of the American Society of Human Genetics.
Dr. Eng’s knowledge, wisdom, and insights are a rare treasure. Her spirited collegiality, unconditional generosity, honest and equitable nature, and her sense of humor endear her to colleagues, collaborators, employees, and trainees alike. Her success and her seeding of other investigators’ successful programs in many venues epitomize the ideals of Ernst Oppenheimer and thus make Dr. Eng a very worthy recipient of the 2006 Oppenheimer Award.
Paul W. Ladenson
Citation for the 2006 Robert H. Williams Distinguished Leadership Award of The Endocrine Society to Dr. Richard J. Santen
Dr. Richard J. Santen is a leading authority in the field of reproductive endocrinology who for more than three decades has worked to increase our understanding of hormone-dependent breast and prostate cancer. His career can be characterized as the synthesizing of mechanisms of reproductive endocrinology and applying these concepts to the development of innovative treatments for hormone-dependent cancer. Together with a group of 98 multidisciplinary, local, national, and international collaborators, he spearheaded the development of aromatase inhibitors for the treatment of breast cancer. For this work he received the Brinker International Award of the Susan B. Komen Foundation. His pre-clinical studies led to the first trial of GnRH agonists for the treatment of prostate cancer in the United States.
Dr. Santen’s contributions bridge the gap between molecular, translational, and clinical research and have resulted in improved care of patients with breast and prostate cancer. On the molecular level he demonstrated that hormonal therapy for breast cancer results in adaptive mechanisms that enhance the level of sensitivity to estrogen through growth factor pathway up-regulation. This "adaptive hypersensitivity" utilizes pathways in which the estrogen receptor acts at the level of the plasma membrane in addition to its action on transcription in the nucleus. His research team explained how high-dose estrogen therapy paradoxically causes breast cancer regression in postmenopausal women through stimulation of a death receptor pathway inducing apoptotic cell death. Translational studies exploited molecular targets with development of a specific inhibitor of mTOR, a key regulator of tumor cell growth.
Dr. Santen’s research teams benefited from his leadership in the initiation of clinical trials of first-generation aromatase inhibitors in comparison with surgical adrenalectomy and the antiestrogen, tamoxifen. Concepts integral to understanding of the GnRH super-agonist analogs for the treatment of breast and prostate cancer were the underlying mechanisms whereby sex steroids exert negative feedback regulation of LH and FSH. Santen and his colleagues designed and utilized the first practical computer approach to examine the effects of estrogens and androgens on pulsatile LH release. His work on breast and prostate cancer, pulsatile LH release, and androgen and estrogen physiology has led to over 250 peer-reviewed publications and 100 review articles, books, and chapters in the leading textbooks of endocrinology.
Dr. Santen benefited enormously from the guidance and encouragement of key mentors early in his career. These included Dr. C. Alvin Paulsen, director of the reproductive endocrinology training program at the University of Washington; Professor Paul Franchimont at the University of Liege; and Dr. Penti Siiteri, who suggested the concept of aromatase inhibition for breast cancer. Dr. C. Wayne Bardin provided the opportunity to participate in a unique and pioneering venture, the initiation of the brand-new Penn State medical school. With few faculty at its inception, this institution rewarded a broad approach to teaching, investigation, patient care, and, most importantly, collaboration—a milieu in which Santen thrived. He was recognized as one of only two clinical faculty to become one of the 23 active university-wide Evan Pugh Faculty Professors.
Dr. Santen’s leadership role manifested itself through service as Division Chief, Department Chair, Cancer Center Associate Director, Chair of The Endocrine Society Finance Committee, and member of the Executive Councils of The Endocrine Society, American Society of Andrology, and International Endocrine Society. Specific contributions to The Endocrine Society included the lead role he took in developing the long-range financial plan that has enabled the Society to invest in new initiatives over the past 7 years. He initiated and nurtured the International Scholars Program of The Endocrine Society, which has identified 25 exceptional trainees from outside the United States, and arranged for outstanding training experiences in laboratories of Endocrine Society members worldwide. He has trained 32 clinical and postdoctoral fellows and inculcates the role of excellence in the care of patients.
Service to the scientific community provides a mark of leadership that characterizes Dr. Santen’s career. His special interest in cancer led to his contributions as a member of the National Institutes of Health (NIH) Clinical Cancer Program Project study section, the VA Merit Review study section, the Department of Defense Breast Cancer Integration Panel, the NIH prostate cancer working group, the advisory boards for the University of Wisconsin Cancer Center, the Mayo Clinic Breast Cancer Spore, the Lombardy Cancer Center at Georgetown University, the Eppley Cancer Institute of the University of Nebraska, the De Costa Breast Cancer Prevention Foundation, and the NIH Cancer Cube Focus group. He was a founding member of the series of seven International Aromatase meetings that served as a catalyst for collaboration among aromatase inhibitor investigators. His reproductive interests involved him in an evaluation group for the World Health Organization Male Reproduction task force and in serving on the American Board of Internal Medicine Endocrinology committee.
Trained at the University of Washington during Dr. Robert William’s tenure, Dr. Santen provides an example of a leader who fits the eclectic mold that Dr. Williams instilled as one of his first principles. He is truly deserving of the Robert H. Williams Distinguished Leadership Award.
Robert Carey
Citation for the 2006 Edwin B. Astwood Award Lecture of The Endocrine Society to Dr. Mitchell A. Lazar
Mitch Lazar was born on April 24th, 1956, in a U.S. Army Hospital in Frankfurt, Germany. He grew up in Syosset, New York, and graduated from the Massachusetts Institute of Technology (MIT), where he majored in chemistry. Lazar loved organic chemistry and did research with mentors Fred Greene of MIT and Nick Turro of Columbia. But it was the captivating lectures of Hans-Lucas Teuber that led him to go west, seeking to combine chemistry and behavioral science in the lab of Jack Barchas at Stanford Medical School. He soon realized that the biochemistry of behavior was a complex problem whose solution in 1976 was a distant dream, and he thus gravitated toward more "hard-core" biochemistry, focusing on the purification and properties of tyrosine hydroxylase. What thrilled him most was the feedback inhibition of this enzyme, which served to keep intracellular neurotransmitter levels constant. This resonated with the goal of endocrinology to understand maintenance of the milieu interior of the whole organism, leading to Mitch’s passion for this pursuit.
In 1982, Mitch moved back east to complete a medical residency at the Brigham and Women’s Hospital and an endocrine fellowship at the Massachusetts General Hospital (MGH). At MGH, he became skilled in molecular biology in the lab of Hank Kronenberg and developed a penchant for thyroid hormone (TH) action from discussions with Gil Daniels and Doug Ross. The MGH’s flexibility allowed him to join my lab at the Brigham, where Mitch proceeded to discover two novel forms of the thyroid hormone receptor (TR). He also discovered one of the first "orphan" receptors, named Rev-erb
, because it was encoded on the opposite strand of the gene for c-erbA, another name for the form of thyroid hormone receptor. Working together with Rich Hodin, Lazar unraveled this complex genomic relationship before the days of PCR and automated sequencing.
Among the thyroid receptors Mitch uncovered was splicing variant TR2, which does not bind thyroid hormone. In 2006, this seems almost obvious as TR2 lacks the TH-binding domain. In 1986, however, ligand binding mechanisms were not well understood, and the failure of this putative TR to bind TH was a conundrum that Mitch was determined to understand before publishing the cloning of TR2. Meanwhile, two high-profile papers independently described TR2 as a TH-binding receptor! Mitch persevered and, together with Ron Koenig, Reed Larsen, and David Moore, convincingly showed that the "negative result" was the true one, and actually quite interesting because TR2 functions as a dominant inhibitor of TH action. This illustrates the scientific creativity, quality, and integrity that have characterized his work from an early stage.
Mitch left my lab in 1989 to become Assistant Professor in the Endocrinology Division at the University of Pennsylvania School of Medicine. Over the past 17 years he has risen up the academic ranks to his current position as Sylvan Eisman Professor of Medicine, Chief of the Division of Endocrinology, and Director of the Institute for Diabetes, Obesity, and Metabolism at Penn. During this remarkably productive period, he has continued his investigation of thyroid hormone receptors and Rev-erb, making important contributions to the role of homo- and heterodimerization in DNA binding and silencing of gene transcription by interaction with corepressors. Mitch ’s most important accomplishments in this area include the discovery of the "CoRNR" motif that mediates interactions between receptors and corepressors, the first purification of an endogenous nuclear receptor corepressor complex, the discovery of a novel function of corepressors as activating cofactors for histone deacetylase 3 (HDAC3), and the demonstration that HDAC3 plays a singularly important role in nuclear receptor-mediated repression. This work has had a major impact on our understanding of hormone action.
Mitch’s most significant contributions concern the growing epidemic of obesity-associated diabetes. A pioneer in the linkage of the nuclear receptor PPAR
to adipocyte differentiation, insulin resistance, and type 2 diabetes, he proposed early on that thiazolidinedione drugs improve insulin sensitivity as a consequence of altering PPAR activity in adipocytes. This view is now widely accepted, due in large part to his scientific contributions. Mitch has discovered unexpected PPAR target genes and identified novel mechanisms of gene regulation by PPAR in adipocytes. Most excitingly, he discovered a new hormone called resistin, which impairs insulin action and provides a link between obesity and insulin resistance. In an elegant series of experiments, he has demonstrated the physiological and pathophysiological importance of resistin in glucose metabolism and insulin resistance.
A superb physician-scientist, Mitch Lazar is a great colleague and an outstanding role model and mentor to students and fellows, several of whom are now running their own laboratories. Much of his motivation, as well as his success, can be attributed to his wonderful wife, Althier, and his two terrific sons, Zachary and Aaron. From gene regulation to physiology, Mitch’s unique contributions to endocrinology make him highly deserving of The Endocrine Society’s 2006 Edward B. Astwood Award and Lecture.
William Chin
Citation for the 2006 Clinical Investigator Award Lecture of The Endocrine Society to Dr. Walter L. Miller
The Endocrine Society is delighted to honor Dr. Walter L. Miller with the Clinical Investigator Award. An outstanding mentor and educator, Dr. Miller has been a consistent and innovative international leader, defining the field of molecular steroidogenesis by integrating basic research with clinical observation. Like the best clinical investigation, his work has changed the way endocrinologists think about this field.
Walt spent his early childhood in a small town in rural Argentina, where his father, a mechanical engineer, supervised a cement plant. From an early age, Walt became a budding chemist. He was intrigued by pyrotechnics, rocketry, and devices for interstellar flight and finished fourth in the Westinghouse Science Fair in 1961. He graduated from the Massachusetts Institute of Technology, where he studied philosophy and biology, in 1965. Walt then spent a year in Ron Malt’s lab at the Massachusetts General Hospital, co-authoring a 1967 paper in the Journal of Experimental Medicine on RNA metabolism during compensatory renal hypertrophy. After graduation from Duke Medical School (1970), he did two years as pediatric resident at Massachusetts General Hospital before joining Fred Bartter (a Koch medalist) as a staff associate in the Endocrine-Hypertension Branch of the National Heart and Lung Institute.
In 1974 he came to the University of California San Francisco (UCSF), first as a senior resident in Pediatrics, then as a Fellow in Brian McCarthy’s lab in the Department of Biochemistry and Biophysics where he studied nucleic acid reassociation kinetics, and finally as a fellow in pediatric endocrinology. He joined the faculty as an Assistant Professor of Pediatrics and began a highly productive collaboration with John Baxter, including the cloning of bovine growth hormone and prolactin cDNAs in 1980.
Walt then embarked on his extraordinarily productive, "state-of-the-art" studies of the clinical disorders, genetics, cell biology, and biochemistry of steroidogenesis. His laboratory cloned many human steroidogenic enzymes and delineated the molecular basis of several endocrine disorders. They showed that cellular steroidogenic capacity is determined by quantities of enzyme mRNAs and correlated fetal adrenal growth with IGF-2. His group was first to propose that gene conversion was the principal genetic mechanism underlying 21-hydroxylase deficiency, discovered the extracellular matrix protein Tenascin-X as a novel gene overlapping the gene for steroid 21-hydroxylase (CYP21), delineated the genetic anatomy of the C4/CYP21/ TNX locus, and identified Tenascin-X deficiency as the cause of recessive Ehlers-Danlos syndrome.
Miller’s group identified the first mutations causing isolated 17,20 lyase deficiency and showed that these mutations disrupted electron transfer to P450c17. They demonstrated that the 17,20 lyase activity of P450c17, required for sex steroid biosynthesis, is regulated posttranslationally by P450c17 phosphorylation and by the allosteric action of cytochrome b5, which both regulate electron transfer. This work provided the first explanation of how adrenal glucocorticoid and androgen synthesis are independently regulated and has had an important impact on current views of the pathogenesis of PCOS.
His laboratory showed that congenital lipoid adrenal hyperplasia is a knockout of the steroidogenic acute regulatory protein (StAR), confirming its biological role; he formulated the two-hit model, explaining its baffling clinical characteristics. His structural analyses show that StAR acts transiently as a molten globule on the outside of mitochondria to facilitate the movement of cholesterol from the outer to the inner mitochondrial membrane. His group also cloned the long-sought vitamin D-1 hydroxylase and showed that its mutations cause vitamin D-dependent rickets. Most recently, Walt’s group discovered P450 oxidoreductase deficiency, a new form of congenital adrenal hyperplasia first found in patients with Antley-Bixler syndrome, an unanticipated link between steroidogenesis, skeletal development, and pharmacogenetics. Indications of his productivity and the impact of his laboratory include his more than 300 published papers and book chapters and the fact that, according to the ISI, his work has been cited nearly 12,000 times.
Walt is Director of the UCSF Division of Pediatric Endocrinology and its NIH-supported Fellowship Training Program. A gifted mentor of fellows and junior faculty, he is an astoundingly accomplished and rigorous but compassionate clinical pediatric endocrinologist, tireless in his pursuit of detail in clinical circumstances, and a superb, Socratic, bedside teacher. In addition to supervising the clinical training of two dozen clinical fellows, more than 70 fellows, trainees, or young faculty have worked in Walt’s laboratory—a rigorous and demanding experience at the bench and in mastering the art of scientific writing and exposition. He has nurtured their growth and fostered independence.
One of Walt’s hobbies is making wine, where he practices biochemistry as an art, rather than as a science. His pinot noir, labeled "Nuit St. Wogga Wogga, mis en boutille dans nos garages," is a highly prized, premium wine—in wine speak he is a "garagiste."
Walt met Synthia Mellon at UCSF, and they have been married for 21 years. Sindy, a longtime member of The Endocrine Society and President of Women in Endocrinology, is a premier investigator of the synthesis and function of neurosteroids.
Walt has lectured in 22 countries and served on many editorial boards, including The Journal of Clinical Endocrinology & Metabolism, Endocrinology, Journal of Endocrinology, DNA and Cell Biology, and Molecular Genetics and Metabolism. He was a member of the Biochemical Endocrinology Study Section and currently serves on the Board of Scientific Counselors, NICHD, and the Basil O’Connor Starter Scholar Research Award Committee of the March of Dimes. He has received many awards and honors, including the Edwin B. Astwood Award from The Endocrine Society, the Albion O. Bernstein Award, the Clinical Endocrinology Trust Medal from the British Endocrine Societies, Henning Andersen Prize of the European Society for Paediatric Research, Samuel Rosenthal Foundation Prize for Excellence in Academic Pediatrics, and election as a Fellow of the American Association for the Advancement of Science.
The Endocrine Society takes special pleasure in recognizing Walt Miller’s extraordinary accomplishment—the breadth, rigor, impact of his work, and his integrated use of a broad array of genetic, biophysical, and clinical approaches to human disease—by awarding him the 2006 Clinical Investigator Award.
Melvin Grumbach
Citation for the 2006 Gerald D. Aurbach Award Lecture of The Endocrine Society to Dr. Paul A. Kelly
Paul Kelly received his Ph.D. in Endocrinology and Reproductive Physiology at the University of Wisconsin in 1972. He undertook postdoctoral training with Henry Friesen and then with Fernand Labrie. After joining Laval University as Assistant and Associate Professor, he moved to McGill University, where he rose rapidly to become Professor of Medicine in the Departments of Experimental Medicine and of Physiology. In 1991 he relocated to France to become Research Director of an INSERM research unit studying molecular endocrinology. He was also appointed Full Professor of Cell Biology of the Necker Faculty of Medicine. Since the year 2000, he has directed the Necker Research Institute (IRNEM), a federation of 24 basic and clinical research structures (750 people) in the context of the largest adult and pediatric university teaching hospital in France.
Paul has been an active leader of The Endocrine Society, serving as Editor of Endocrinology, a long-standing member of the Annual Meetings Steering Committee, and Basic Science Chair of the 2000 Annual Meeting in Toronto. He is also past Chair of the Prolactin Family Gordon Research Conference, where over the years he has been a frequent speaker and discussion leader.
Paul has had a life-long interest in unraveling mechanisms for prolactin action. In fact, he has arguably made the most significant contributions to our understanding of prolactin receptor signaling. In 1973, he and his colleagues R. C. Shiu and Henry Friesen published the first radioreceptor assay for prolactin in Science. This work led to the identification of placental lactogenic hormones in numerous species. These discoveries were followed by prolific seminal studies defining the pathophysiology of prolactin and other lactogenic hormones in animals and ultimately in man. In 1988, culminating 15 years of dogged biochemistry and cell biology, Paul reported the cloning and expression of the rat prolactin receptor in 1988 in Cell. The subsequent 17 years saw an explosive growth of our understanding of lactogenic hormone action based on cellular and transgenic models spawned by this discovery. The receptor cloning studies, originally limited to prolactin and growth hormone, were expanded by numerous other laboratories, which resulted in identification of the class I cytokine receptor superfamily, today comprising over 30 members. The study of the downstream events led to the identification by his group and others of the tyrosine kinase, Jak2, and the Stat proteins as mediators of both prolactin and growth hormone actions.
The development of the mouse model of the knockout of the prolactin receptor, published in Genes & Development in 1997, confirmed that prolactin and its receptor were essential to the process of lactation. Interestingly, this model system also led to the identification of numerous other actions of prolactin, including on maternal behavior, bone development, pancreatic ß-cell growth and insulin secretion, lacrimal gland function, hair development, and immune function. More recently, his laboratory has shown that prolactin exhibits antitumor actions, at least for the anterior pituitary and the thyroid.
His group has pioneered the development of therapeutic molecules acting directly as prolactin receptor agonists and antagonists. The most recent pure antagonist is currently being tested in animal model systems of breast cancer and prostate hypertrophy and cancer.
Perhaps Dr. Kelly’s greatest contributions have been his ever-ready generosity in sharing reagents and transgenic animals and collaborating with multi-faceted investigators worldwide. This has resulted in the entire field of prolactin action in breast, reproductive, adipose, cardiovascular, and cancer tissues being subserved by the creative discoveries emanating from his laboratory. Paul has also carefully nurtured the careers of dozens of young colleagues who have benefited from his wisdom, integrity, and warm personality. The Endocrine Society is proud to honor this researcher, teacher, and leader of the endocrine community.
Shlomo Melmed
Citation for the 2006 Sidney H. Ingbar Distinguished Service Award of The Endocrine Society to Dr. Robert D. Utiger
Robert D. Utiger, M.D. is the 2006 recipient of the Sidney H. Ingbar Distinguished Service Award, presented for pioneering investigation, training of young endocrinologists, service on the committees that set the standards for how physicians are trained and tested, and editorships of major medical publications.
Dr. Utiger began his medical career at Washington University and the NIH, where in the late 1960s he developed the first immunoassay for TSH. A few years later, at the University of Pennsylvania, he developed one of the first immunoassays for triiodothyronine. He then used these assays to elucidate the physiology of the hypothalamic-pituitary-thyroid axis. In 2006, try to imagine practicing endocrinology without these assays and without the resulting knowledge of the function of this axis! For these discoveries he was elected to the American Society of Clinical Investigation and the Association of American Physicians and received the Van Meter Award of the American Thyroid Association.
While at the University of Pennsylvania, as Chief of Endocrinology and Professor of Medicine, he began to train young endocrinologists, which he has continued at the University of North Carolina and now at Harvard Medical School and the Brigham and Women’s Hospital.
Also while at the University of Pennsylvania, he began to serve on the committees that set the standards for how endocrinologists and other physicians are trained and tested. He was asked to serve on committee after committee, because of his high standards yet fairness. For over 30 years he served on the National Board of Medical Examiners, as a member of several test committees and as a member of the Board itself. He twice served as a member of American College of Physicians Medical Knowledge Self-Assessment Program in Endocrinology and Metabolism Committee. He served as a member and then chair of the American Board of Internal Medicine’s Endocrinology and Metabolism Test Committee and a member of the Board itself.
For over 20 years his major service has been as editor of major medical journals. For six years he was Editor-in-Chief of The Journal of Clinical of Endocrinology & Metabolism, and for 11 years Deputy Editor of the New England Journal of Medicine. In these positions his high scientific standards, high standards for clarity of expression, and fairness could be appreciated by reviewers and by authors. He was also Co-Editor-in-Chief of UpToDate in Endocrinology and Metabolism, and currently he is Editor-in-Chief of Clinical Thyroidology. And for its last four editions, he has been Co-Editor of The Thyroid, the leading text of thyroidology, of which Dr. Ingbar was once Editor.
He has also served The Endocrine Society. In addition to Editorship of The Journal of Clinical Endocrinology & Metabolism, he was a member and chair of the program committee and a member and chair of the awards committee.
With this award The Endocrine Society honors Dr. Utiger and also itself.
Peter Snyder
Citation for the 2006 Roy O. Greep Award Lecture of The Endocrine Society to Dr. Benita S. Katzenellenbogen and Dr. John A. Katzenellenbogen
Dr. Benita S. Katzenellenbogen and Dr. John A. Katzenellenbogen are the joint recipients of the 2006 Roy O. Greep Lecture Award, given in recognition of their enormous contributions to our understanding of the actions of estrogens and structure-function relationships in estrogen receptors and their diverse ligands.
Benita Katzenellenbogen, Ph.D., received her B.A. from The City University of New York and her Ph.D. from Harvard University for studies in cell and developmental biology with Dr. Fotis Kafatos. After a brief postdoctoral fellowship studying estrogen receptor action with Dr. Jack Gorksi at the University of Illinois, Urbana, she joined the faculty as an Assistant Professor of Physiology and Biophysics at the University of Illinois and College of Medicine at Urbana-Champaign. She is currently the Swanlund Chaired Professor of Molecular and Integrative Physiology at Illinois.
John A. Katzenellenbogen, Ph.D., received his A.B. degree from Harvard University and his Ph.D. degree for his graduate studies in chemical synthesis with Professor E. J. Corey at Harvard. He then became an Assistant Professor in the Department of Chemistry at the University of Illinois at Urbana-Champaign, where he is currently the Swanlund Chaired Professor of Chemistry.
These two outstanding scientists have each had extremely distinguished, independent scientific careers, as well as extraordinarily productive collaborations involving novel estrogen receptor ligands synthesized in John Katzenellenbogen’s laboratory and utilized in Benita Katzenellenbogen’s laboratory to characterize estrogen receptors and understand the unique biologies of estrogen receptors and ß.
Dr. Benita Katzenellenbogen is at the forefront in defining structure-function relationships and the actions of the estrogen receptor (ER) in breast cancer and normal tissues, as well as the molecular basis of action of antiestrogens/SERMs. Her laboratory was the first to demonstrate that ER responds to multiple cell signaling pathways involving cAMP, kinase cascades, and growth factors such as IGF-I, illuminating the manner in which phosphorylation modulates receptor activity. In addition, she and her associates have identified proteins that enhance antiestrogen potency and discovered and cloned REA, a repressor of estrogen receptor activity. REA competes with coactivators for binding to ER and mutes the magnitude of estrogen action; its elimination in cellular and animal knockout contexts markedly enhances estrogen responses. She has cloned tamoxifen-induced target genes, including quinone reductase, indicating the importance of antioxidant activity in tamoxifen therapy. Finally, her laboratory has elucidated the many gene networks and pathways under estrogen and SERM regulation, providing new insights into the patterns of gene regulation that are responsible for the proliferative, antiapoptotic, and cytoarchitectural effects of estrogens in breast cancer cells.
Dr. John Katzenellenbogen’s research has been directed at important aspects of the structure, function, and use of estrogen ligands and steroid receptors in various analytical and biomedical applications. He and his associates prepared the first affinity labeling agent for the estrogen receptor, tamoxifen aziridine, and have synthesized and evaluated many receptor ligands having novel structures and activities, including those most selective for the estrogen receptor subtypes, ER and ERß. His laboratory has developed an extensive series of steroid receptor-based agents, labeled with fluorine-18 and technetium-99m, for imaging receptor-positive tumors of the breast and prostate by positron emission tomography (PET), and he was the first to image these tumors based on their content of estrogen or androgen receptors. More recently, he has initiated biochemical and biophysical studies on the dynamics of receptor interaction with coregulator proteins.
Among their many joint accomplishments are the synthesis and use of a novel estrogen receptor affinity label, in 1984, to define the physical properties and half-life of the estrogen receptor in target tissues and cells; the identification of an estrogenic contaminant in phenol red that enabled estrogen action to be studied in cell culture systems; the development and use of highly selective ligands to study ER and ERß function, and, most recently, the preparation and use of estrogen-dendrimer conjugates to study the extra-nuclear actions of estrogen receptors.
Benita and John Katzenellenbogen have received many awards for their scientific contributions. Benita has received the Ernst Oppenheimer Award from The Endocrine Society, the Scientific Distinction Award from the Susan G. Komen Breast Cancer Foundation, the Jill Rose Award from the Breast Cancer Research Foundation, and the Faculty Member of the Year Award from the University of Illinois College of Medicine. John’s many awards include the Berson Yalow Award and the Paul C. Aebersold Award from the Society of Nuclear Medicine and the Cope Scholar Award from the American Chemical Society. Both have been elected Fellows of the American Academy of Arts and Sciences.
Nancy Weigel
Citation for the 2006 Distinguished Educator Award of The Endocrine Society to Dr. Gilbert H. Daniels
Gilbert Harlan Daniels was born in Brooklyn, New York, attending Valley Stream North High School before entering Yale University, from which he graduated with a Bachelors of Science. Gil matriculated at Harvard Medical School, graduating in 1966. He did his internship and residency in internal medicine under the intense and critical preceptorship of Sam Thier at the Massachusetts General Hospital (MGH) in a group of other interns that included Drs. Michael Brown and Joel Goldstein, both eventual Nobel Prize recipients. After his residency he migrated to the NIH and performed basic research in the Seymour Kaufman Laboratory of Neurochemistry at the National Institute of Mental Health in Bethesda. He was a clinical fellow in 1970 at the University of California at San Francisco, where he was mentored by Hibbard Williams and Francis Greenspan. Gil then returned to Boston where he was Senior Resident and Chief Resident in internal medicine at the MGH. He has been there ever since and is currently Professor of Medicine.
Gil’s imprint on clinical endocrinology has been felt in every corner of the United States. This was largely accomplished by his masterful leadership of the Clinical Endocrine Fellowship Program of the MGH under John Potts for 23 years between 1973 and 1996, as well as his direction of the highly successful and respected MGH Post-Graduate Course. He has been Director or Co-Director of the Thyroid Clinic at the MGH since 1982 and continues with a prodigious clinical practice at the MGH. Gil is called weekly from all over the U.S. to answer clinical or education questions in the field of endocrinology.
His clinical scholarship has been outstanding, with over 100 original pieces of work, many of which are considered classics. For instance, in his 2004 JAMA publication on subclinical thyroid disease Gil had the unenviable task of calming a caldron of diverse positions. He has made contributions to the most important text of thyroidology, Werner and Ingbar’s The Thyroid. From a national and international perspective, his contributions to Harrison’s Principles of Internal Medicine since 1987 have been another major accomplishment.
In 1999, Gil was honored with the Distinguished Clinician Award of the American College of Endocrinology. Additionally, Gil has held important leadership positions in all of the major societies representing clinical endocrinology, including the American Thyroid Association, The Endocrine Society, and the American Association of Clinical Endocrinologists. Gil has served on the editorial board of multiple journals, most importantly The Journal of Clinical Endocrinology & Metabolism. He has also been an ad hoc reviewer for the New England Journal of Medicine, JCI, JAMA, Thyroid, and Archives of Internal Medicine.
At the 1999 Annual Meeting of The Endocrine Society, I sat in awe as Dr. Daniel Federman received and accepted this award for his remarkable achievements in endocrinology scholarship and education. I knew then that Gil Daniels, who had emulated Dan’s mastery of the power of blackboard teaching, should soon achieve this same well-deserved recognition. In my mind, Gil has taken the concept of scholarship in clinical endocrinology to a new level because of his own contributions as a clinical scientist and his low tolerance for poor scholarship and sloppy clinical medicine. His influence extends nationally, as he has become the gold standard for other academic clinical endocrinologists in the country. He has trained many of the most successful clinical and academic endocrinologists in this country. He is sought for clinical teaching by all of the most venerated endocrinology education programs in the United States.
I would like to join hundreds, and perhaps thousands, of endocrinologists in this country and abroad in saying "Thank God for Gil Daniels and his sustained commitment to excellence in endocrine education."
E. Chester Ridgway
Citation of the 2006 Distinguished Physician Award of The Endocrine Society to Dr. Glenn D. Braunstein
Glenn Braunstein obtained his M.D. degree at the University of California San Francisco (UCSF) in 1968. After completing medical residency at the Peter Bent Brigham Hospital and Endocrinology training at the National Institute of Health and Harbor General Hospital, he was recruited to Cedars-Sinai Medical Center in 1973 to establish an academic division of endocrinology. From 1973 until 1986, he served as Director of the Division of Endocrinology. During that period the division increased from one full-time member (himself!) and a few attending physicians to 40 full-time faculty and voluntary attending staff. He developed an NIH fellowship training program in concert with the West Los Angeles Veterans Administration and the division was well supported by NIH grants. In 1986, he was appointed Chairman of the Department of Medicine. He is Professor of Medicine at the David Geffen School of Medicine at the University of California Los Angeles (UCLA) and holds the James R. Klinenberg Chair in Medicine at Cedars-Sinai Medical Center. Under his leadership, the Department of Medicine has flourished and shown consistent growth and productivity over the last 20 years. The Department of Medicine has grown to comprise 700 full-time and voluntary attending physicians, 150 residents and fellows with a consistently outstanding Internal Medicine Board passage rate. The department has $33 million in research awards, with an annual growth rate of 9%.
In addition to his prolific research achievements and onerous but highly successful administrative responsibilities, Dr. Braunstein has sustained a superb practice of hands-on clinical medicine. His management of patients with menopausal disorders, gynecomastia, hypogonadism, menopausal androgen deficiency, and thyroid cancer are unparalleled in our community. He is ranked one of "America’s Best Doctors," as well as by LA Magazine as one of the best endocrinologists in Los Angeles. He was named the "Master of Medicine–Top Endocrinologist" in Los Angeles by the Los Angeles Business Journal.
Dr. Braunstein’s outstanding peer recognition has been reflected in his election as a Director of the American Board of Internal Medicine and Chairman of the Subspecialty Board of Endocrinology, Diabetes and Metabolism. This well-deserved honor confirmed Dr. Braunstein as a national leader in clinical endocrinology. He currently leads a portion of the ABIM Self-Evaluation Process Test Committee for Endocrinology. He recently completed serving a second tenure as Chair of the FDA’s Endocrinologic and Metabolic Drug Advisory Committee and was elected as Internal Medicine’s representative to the American Board of Emergency Medicine. He is the consummate and highly effective ambassador for clinical endocrinology on these prestigious national bodies.
He is the honored recipient of the Morris Press Humanism Award (1984) from Cedars-Sinai Medical Center and the Sherman M. Mellinkoff Faculty Award given by the UCLA School of Medicine (2002) for a faculty member whose teaching exemplifies dedication to the art of Medicine and to the finest in doctor-patient relationships.
Dr. Braunstein is a preeminent clinical scientist in the field of placental hormones. His prolific C.V. attests to his scientific achievements and scholarly original contributions to clinical endocrinology. Early in his career, in collaboration with Judy Vaitukaitis and Griff Ross, Glenn developed the original ß-hCG radioimmunoassay, which was the prototype for all of the modern sensitive and specific pregnancy tests. Our understanding of the syndrome of ectopic and eutopic tumor hormone production, which is so well recognized today, is in no small part due to his original observations and discoveries over 30 years ago. His laboratory at Cedars-Sinai has been focused primarily on basic and clinical studies of placental protein hormones, and his accomplishments include an early description of subclinical spontaneous abortion (occult pregnancy); the finding that a wide variety of normal adult, nonpregnant tissues contain small quantities of hCG; the observation that some postmenopausal women secrete excessive quantities of hCG from their pituitary; and demonstrating the intrinsic differences in hormone production between first and third-trimester trophoblasts grown in vitro. More recently, he has been a principal investigator in studies that have shown the efficacy and short-term safety of testosterone treatment of hypoactive sexual desire disorder in surgically menopausal women and has published a series of studies that have examined the various parameters that affect the efficacy of radioactive iodine treatment of thyroid cancer.
Glenn is the master physician-teacher, the "doctor of doctors," and the exemplary distinguished physician and consultant for patients with endocrine disorders. His teaching and patient care dedication exemplify the finest in clinical contributions and his leadership roles in American Medicine.
Shlomo Melmed
Citation of the 2006 Richard E. Weitzman Memorial Award of The Endocrine Society to Dr. Fabio Broglio
Dr. Fabio Broglio is an emerging leader in the field of clinical endocrinology. He has primarily focused his research on the endocrine, metabolic, and cardiovascular actions of ghrelin and its synthetic analogs in man, both in physiological and pathological conditions. He is the recipient of the 2005 Richard E. Weitzman Memorial Award, which is to honor an exceptionally promising young clinical or basic investigator in the field of endocrine research.
Dr. Broglio, who is Assistant Professor of Endocrinology at the University of Turin, began his research career in 1994 when as a medical student he started his internship in the School of Endocrinology at the University of Turin under the supervision of Prof. Ezio Ghigo. He began working in the field of growth hormone secretagogues. These studies described the GH-releasing effect of hexarelin across lifespan in physiological conditions as a function of gender and identified the role of sex steroids in the modulation of somatotroph responsiveness to GH secretagogues.
After graduation from medical school, Fabio Broglio extended his interest in the characterization of the activity of the somatotroph axis in pathological conditions, in particular in patients with dilated cardiomyopathy. Fabio conducted pioneering studies that provided for the first time a comprehensive description of the physiology of the GH/IGF-I axis, in terms of spontaneous GH secretion, somatotroph responsiveness to classical stimuli and GH Secretagogues, as well as peripheral GH sensitivity in patients with chronic heart failure.
In these same years, after reports of specific binding sites for GH secretagogues in myocardial tissue, Fabio began a long-lasting project that elucidated for the first time positive cardiotropic effects of peptidyl GH secretagogues, namely hexarelin, in normal subjects, patients with GH deficiency, patients with dilated and postischemic dilated cardiomyopathy, and patients with ischemic heart disease. These results indicated a positive inotropic effect of hexarelin in patients with GH deficiency, proposing a new and original concept that GH secretagogues do not exclusively act via stimulation of somatotroph action but also exert independent peripheral actions.
After the isolation in 1999 of ghrelin as a new gastric hormone and endogenous ligand of GH secretagogue receptors, Fabio tested the physiological relevance of most of his previous results with synthetic GHS. The group in Turin was the first reporting a GH-releasing effect of exogenous ghrelin administration in humans and to study its interactions with GHRH, somatostatin, cholinergic agonists and antagonists, and metabolic fuels such as free fatty acids and glucose. Fabio’s group was the first reporting a GH-independent effect of ghrelin on insulin secretion and, independently, on glucose metabolism. This opened interesting new perspectives for this hormone as a modulator of energy metabolism rather than simply being a natural GH secretagogue.
Taking advantage of his previous experience in the neuroendocrine control of GH secretion, Fabio Broglio then described some of the neuroendocrine factors controlling ghrelin secretion, reporting for the first time in humans that somatostatin represents the most potent inhibitory input on ghrelin secretion known so far and, on the other hand, that cholinergic agonism is one of the few stimulatory inputs on ghrelin secretion.
The interest in the ghrelin field led Dr. Broglio’s research also to characterize in humans for the first time the endocrine and metabolic actions of cortistatin, a cortical neurohormone sharing high structural homology, and its known five receptor subtypes with native somatostatin, but not all its central actions. The report that cortistatin, but not somatostatin, also binds ghrelin receptors prompted studies on this neuropeptide, which are currently carried out by several groups with promising perspectives.
More recently Fabio focused his interest on unacylated ghrelin, originally considered as an inactive variant of acylated, active ghrelin. He recently described for the fist time that also the unacylated form of ghrelin is biologically active in humans and probably plays an interesting and unexpected role in glucose metabolism.
Steven W. J. Lamberts
Citation for The Endocrine Society and Pfizer, Inc. International Award for Excellence in Published Clinical Research in The Journal of Clinical Endocrinology & Metabolism
Finalist Awards
"Fibroblast Growth Factor 7: An Inhibitor of Phosphate Transport Derived from Oncogenic Osteomalacia-Causing Tumors." Vol. 90, No. 2, p. 1012–1020. Authors: Thomas O. Carpenter, Bruce K. Ellis, Karl L. Insogna, William M. Philbrick, John Sterpka, and Richard Shimkets. Endocrine Sections of the Departments of Pediatrics (T.O.C., B.K.E.) and Internal Medicine (K.L.I., W.M.P., J.S.), Yale University School of Medicine, New Haven, Connecticut 06520; and CuraGen Corp. (R.S.), New Haven, Connecticut 06511.
"Genetic Classification of Benign and Malignant Thyroid Follicular Neoplasia Based on a Three-Gene Combination." Vol. 90, No. 5, p. 2512–2521. Authors: Frank Weber, Lei Shen, Micheala A. Aldred, Carl D. Morrison, Andrea Frilling, Motoyasu Saji, Frank Schuppert, Christoph E. Broelsch, Matthew D. Ringel, and Charis Eng. Clinical Cancer Genetics Program (F.W., C.E.), Human Cancer Genetics Program (F.W., M.D.R., C.E.), Comprehensive Cancer Center (M.S., M.D.R., C.E.), and Divisions of Endocrinology and Metabolism (M.S., M.D.R.) and Human Genetics (C.E.), Department of Internal Medicine, Department of Molecular Virology, Immunology and Medical Genetics (F.W., C.E.), Division of Epidemiology and Biometrics (L.S.), Department of Pathology (C.D.M.), The Ohio State University, Columbus, Ohio 43210; Department of General Surgery and Transplantation (F.W., A.F., C.E.B.), University of Essen, 45122 Essen, Germany; Department of Internal Medicine (F.S.), Hospital Bad Oeynhausen, 32545 Bad Oeynhausen, Germany; Division of Medical Genetics (M.A.A.), University of Leicester, Leicester LE1 7RH, United Kingdom; and Cancer Research UK Human Cancer Genetics Research Group (C.E.), University of Cambridge, Cambridge CB2 1XZ, United Kingdom.
"High Sensitivity of Human Melatonin, Alertness, Thermoregulation, and Heart Rate to Short Wavelength Light." Vol. 90, No. 3, p. 1311–1316. Authors: Christian Cajochen, Mirjam Münch, Szymon Kobialka, Kurt Kräuchi, Roland Steiner, Peter Oelhafen, Selim Orgül, and Anna Wirz-Justice. Centre for Chronobiology (C.C., M.M., S.K., K.K., A.W.-J.), Psychiatric University Clinic, CH-4025 Basel, Switzerland; Institute of Physics (R.S., P.O.), University of Basel, CH-4056 Basel, Switzerland; and Eye Clinic, University Hospital (S.O.), CH-4012 Basel, Switzerland.
"Kisspeptin-54 Stimulates the Hypothalamic-Pituitary Gonadal Axis in Human Males." Vol. 90, No. 12, p. 6609–6615. Authors: Waljit S. Dhillo, Owais B. Chaudhri, Michael Patterson, Emily L. Thompson, Kevin G. Murphy, Michael K. Badman, Barbara M. McGowan, Vian Amber, Sejal Patel, Mohammad A. Ghatei, and Stephen R. Bloom. Department of Metabolic Medicine, Faculty of Medicine, Imperial College London, Hammersmith Hospital, London W12 ONN, United Kingdom.
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