Citation for the 2008 Fred Conrad Koch Award of The Endocrine Society to Dr. P. Reed Larsen
Dr. P. Reed Larsen has been an exceptional leader and pioneer in the discovery of mechanisms involved in thyroid hormone action and metabolism, and their implications for thyroid hormone homeostasis in health and disease. Initially, as a fellow with Jan Wolff at the NIH, he studied iodide transport. Later, at the University of Pittsburgh, he developed radioimmunoassays for T3 and T4 to study the physiology of these hormones and their utility in clinical endocrinology. Subsequently, he developed sensitive immunoassays for T4 and TSH in dried blood samples. Using these, he cofounded the New England Congenital Hypothyroidism screening program. For many years, he supplied extensive technical support for this and other programs in the United States. The success of these programs came full circle recently when a medical student who was diagnosed and successfully treated for congenital hypothyroidism joined his laboratory.
At the same time, the Larsen team set in motion a series of seminal discoveries that would resonate in the endocrinology field and beyond, including the mechanism by which T4 regulates TSH secretion, the identification and biochemical characterization of the type 2 iodothyronine deiodinase, its susceptibility to proteasomal degradation, and the tissue-specific regulation of T3 concentrations by iodothyronine deiodinases. Perhaps his single most important contribution was the identification of the mechanism by which eukaryotic cells cotranslationally incorporate selenocysteine into selenoproteins, which was established after his group cloned the first member of the selenodeiodinase family.
Most recently, he and his colleagues identified the first patient with “consumptive hypothyroidism”, due to overexpression of the thyroid hormone-inactivating type 3 deiodinase in a hepatic hemangioma. His scholarly work has resulted in over 300 papers, chapters, and review articles. Over time, he has accumulated about 8,500 non-self citations, an H factor of 72 and, remarkably, is the author of the three most highly cited papers in the deiodinase field.
Reed Larsen was born in Cincinnati, OH. He received his A.B. from Princeton and his M.D. from Columbia University. He served his internship and residency at Columbia-Presbyterian Medical Center, New York. He moved to the NIH in Bethesda where he served as a Clinical Associate in the Clinical Endocrinology Branch of the present NIDDK (National Institute of Diabetes, Digestive and Kidney Diseases). After completing his fellowship at University of Cincinnati, he was recruited as Assistant Professor to the University of Pittsburgh School of Medicine where he rose to the rank of Associate Professor. In 1974, Dr. Larsen was recruited as Chief of the Thyroid Division of what is now the Brigham and Women’s Hospital in Boston and from 2002–2007 served as Chief of the Division of Endocrinology, Diabetes and Hypertension. He has been a member of the Harvard Medical School faculty since 1974, was appointed Professorof Medicine in 1982, and for 17 years was a Howard Hughes Investigator.
His research has been widely recognized by the scientific community. He is the recipient of the Van Meter-Armour Prize, the Distinguished Lectureship Award, and the Pathophysiology Award from the American Thyroid Association; the Merck Prize from the European Thyroid Association; the Award for a Distinguished Career in Clinical Investigation from Columbia-Presbyterian Medical Center; the Knoll Pharmaceuticals Mentor Award and the Edwin B. Astwood Lectureship from The Endocrine Society.
Reed Larsen is a delightful person, inspirational mentor, devoted and enthusiastic scientist and, above all, fun to be around. These virtues have attracted young scientists from the US and around the world who have sought to understand the intricacies of thyroid hormone metabolism and action while allowing him to flourish as a gifted mentor. Reed has directly identified and promoted more than two-dozen highly successful leaders in academic medicine, and for his contributions he was recently awarded the William Silen Lifetime Achievement in Mentoring Award by Harvard Medical School.
He is a distinguished member of the American Thyroid Association (Director, 1982–1987; President, 1993–1994), Endocrine Society, American Society for Clinical Investigation, Association of American Physicians and a Fellow of the Royal College of Physicians (London). He has served on many editorial boards and is currently Co-Editor of Williams Textbook of Endocrinology and Editor-in-Chief, Nature Clinical Practice Endocrinology and Metabolism.
Reed Larsen’s research accomplishments have provided extraordinary new insights into basic concepts of thyroid hormone action and metabolism, for which he has been selected as this year’s recipient of the Fred Conrad Koch Award.
Antonio C. Bianco
Citation for the 2008 Ernst Oppenheimer Award of The Endocrine Society to Dr. Joel K. Elmquist and to Dr. Randy J. Seeley
Dr. Joel Elmquist is the 2008 recipient of the Ernst Oppenheimer Award of The Endocrine Society for his studies identifying sites in the brain that underlie the coordinated control of food intake, body weight and glucose homeostasis. Dr. Elmquist is currently the Maclin Family Professor of Medical Science in the Departments of Internal Medicine, Pharmacology, and Psychiatry at The University of Texas Southwestern Medical Center in Dallas. He is also director of the Division of Hypothalamic Research. Prior to his arrival at UTSW in January of 2006, he was an Associate Professor of Medicine and Neurology at Harvard Medical School. Dr. Elmquist is an author on over 100 peer reviewed scientific articles, several invited reviews and book chapters.
Dr. Elmquist was born in 1967 and grew up on a farm in western Iowa. Dr. Elmquist received his Ph.D. in Anatomy and Neuroscience in 1993 and his degree in Doctor of Veterinary Medicine in 1992, both from Iowa State University. In 1994 Dr. Elmquist moved to Boston for postdoctoral training in the laboratory of Dr. Clifford B. Saper in the Department of Neurology at Beth Israel Deaconess Medical Center and Harvard Medical School. During this time, Dr. Elmquist received training in systems neuroscience, functional neuroanatomy, and autonomic physiology. His postdoctoral work focused identifying the pathways in the brain that regulate body temperature and control the coordinated responses to systemic infections, especially fever. During this time, Drs. Elmquist and Saper published several papers and established a longstanding collaborative relationship that continues to this day. The training in the Saper laboratory facilitated the transition of his research work into investigating the pathways that regulate body weight and glucose homeostasis. This was first evidenced by collaborative work investigating CNS targets of leptin between Drs. Rex Ahima and Jeffrey Flier and Elmquist and Saper. This work mapping leptin-responsive neurons was some of the first done following the discovery of leptin and laid the groundwork for the development of Dr. Elmquist’s independent research program.
In 1996, Dr. Elmquist joined the Division of Endocrinology, Diabetes, and Metabolism at Beth Israel Deaconess Medical Center and Harvard Medical School. The rich research environment in the Endocrine Division at BIDMC (Drs. Barbara Kahn, Terry Maratos Flier, Jeffrey Flier, Brad Lowell, Tony Hollenberg and others), allowed Dr. Elmquist’s program to grow. Shortly after moving to the Endocrine Division, Dr. Elmquist developed a long and fruitful collaborative program with Dr. Bradford Lowell. This unique collaboration merged the expertise of Dr. Lowell in mouse genetics and Dr. Elmquist’s background in functional neuroanatomy. In short, they set out to use the power of mouse genetics to unravel the central pathways regulating coordinated energy homeostasis, and to establish the relevant molecules (neuropeptides, neurotransmitters, receptors, intracellular signaling pathways) that operate within these neural circuits.
This work proved to be quite timely and potentially important, as over the past decade it has become clear that while abnormalities in peripheral tissues contribute to the pathogenesis of obesity and type 2 diabetes, these effects are in part due dysregulation of key pathways in the brain. However, it was first necessary to identify the key CNS circuits underlying body weight and glucose homeostasis. Towards these goals, Dr. Elmquist and colleagues have developed several unique mouse models that allow neuron-specific manipulation of key genes regulating neuronal function and responses to key metabolic signals such as leptin and ghrelin.
This combined research program has focused primarily, but not exclusively, on using Cre/lox technology to perturb specific genes in narrow subsets of neurons. A comprehensive program in this area required the generation of numerous transgenic mice in which expression of Cre is directed to different sub-populations of neurons and, as companions for these Cre mice, mutant mice bearing “loxed” alleles of relevant genes. The Elmquist / Lowell collaborative effort used using state-of-the-art cloning methods to direct expression of Cre to chemically identified neurons (e.g. POMC-Cre, SF1-Cre, SIM1-Cre, etc.). Gene targeting methods were used to create the various loxed alleles. As can be seen by several high profile papers published over the past several years, this approach has already resulted in important observations. Several results were unexpected that required the rethinking of existing models. Despite the aforementioned successes, the power of this line of investigation is only beginning to be realized. Indeed, now that these unique mouse models are being used by Dr. Elmquist and his colleagues as well as being widely available to the field, it is certain that interesting and unexpected findings will emerge over the next decade. This will aid in understanding how the nervous system regulates feeding, body weight, insulin secretion by the pancreas, and glucose homeostasis. This is exceptionally important if we are to understand the causes and to develop treatments for obesity and type 2 diabetes.
Barbara B. Kahn
Randy J Seeley, Ph.D. is the winner of the 2008 Ernst Oppenheimer Award of the Endocrine Society. His studies on the regulation of food intake have led to major advances in the understanding of energy balance and body weight regulation, and have provided key targets for the development of treatments for obesity and type 2 diabetes.
Randy Seeley received his Ph.D in Psychology and Behavioral Neuroscience from the University of Pennsylvania in 1993. His thesis mentor was Dr. Harvey Grill, and his doctoral work focused on the brainstem regulation of food intake. Dr. Seeley completed post-doctoral work under the mentorship of Dr. Stephen Woods at the University of Washington. While in Seattle, Dr. Seeley’s research emphasis broadened to the hypothalamic regulation of body weight, including investigation of the role of insulin as an adiposity signal. He was appointed to the faculty at the University of Washington at the conclusion of his postdoctoral training, and his early period as an independent investigator was marked by a series of important and highly influential studies. After the identification of leptin in 1994, Dr. Seeley was the first to demonstrate the anorectic effect of central leptin in healthy outbred rodents. In a subsequent study he was the first to demonstrate that signaling through the melanocortin receptor is a major pathway necessary for leptin action. He also demonstrated that the actions of signals that control long term energy balance, such as leptin and insulin, have distinct properties and sites of action compared to short-term satiety signals. These findings contributed to the fundamental model of CNS regulation of energy balance that exists today, with anabolic and catabolic signaling pathways integrated in key brain regions to regulate homeostasis.
Dr. Seeley was recruited to the University of Cincinnati in 1997 where he founded the Obesity Research Center and rose rapidly to the rank of Professor. His lab continued to identify key mediators of feeding behavior including a series of important studies characterizing the role of agouti-related protein to activate the MC-4 receptor and reduce food intake. In addition, his group demonstrated that the cytokine GM-CSF is made in the brain and influences energy homeostasis.
Beyond his work with leptin and MC-4 signaling, Dr. Seeley group has demonstrated important functions for the gut-brain peptide GLP-1 in the regulation of feeding. These studies have delineated the key distinction between anorexia occurring as a part of energy homeostasis and anorexia arising from toxic exposure or illness. These findings have important implications for clinical medicine in that GLP-1 receptor agonists currently in use to treat diabetes are noted to cause weight loss and nausea as a benefit and side effect of therapy. Even more interesting is a recent finding from his lab that GLP-1 action in the arcuate nucleus has specific effects to augment insulin release, suppress hepatic glucose production and improve glucose tolerance. This work on central effects of GLP-1 to control glucose metabolism is also highly relevant to understanding how several new medications based on GLP-1 receptor signaling mediate their therapeutic effects.
More recently Dr. Seeley has initiated signals to identify how nutrient signals affect key brain nuclei involved in feeding. He and his colleagues demonstrated that the amino acid leucine acts as a signal of positive energy balance in the hypothalamus. This action is signaled through the mammalian target of rapamycin (mTOR), a fundamental mediator of nutrient sensing in eukaryotes, and the first specific action attributed to this pathway in the mammalian brain. This novel observation provides a plausible mechanism for the integration of short-term nutrient signals in the hypothalamus, the center of energy balance regulation.
Taken together Dr. Seeley’s work has been critical in shaping the current understanding of energy balance and body weight regulation. His work is marked by an integration of physiology, pharmacology, neuroanatomy, molecular biology, behavioral neuroscience, and clinical medicine, a breadth of expertise that is both powerful and rare. Importantly his studies have direct implications for the pathogenesis of obesity and are of great clinical relevance. His productivity has been extraordinary and he has become one of the most influential scientists in the field of obesity and metabolism in just over a decade of independent work. Based on these accomplishments he is a worthy recipient of the Endocrine Society’s Ernst Oppenheimer Award.
David A. D'Alessio
Citation for the 2008 Robert H. Williams Distinguished Leadership Award of The Endocrine Society to Dr. Ron G. Rosenfeld
Ron G. Rosenfeld, M.D. is the recipient of the 2008 Robert H. Williams Distinguished Leadership Award presented for his pioneering work on the molecular patho-physiology of growth disorders, the training of pediatric endocrinologists, his outstanding teaching, and his service to the field.
Ron’s training was impeccable: Summa Cum laude undergraduate training in Columbia University, and then Medical School and residency at Stanford University with the highest honors. Originally thinking he was destined for a career in clinical care, he spent a year in clinical practice in pediatrics, but his remarkable thirst for academic knowledge brought him back to Stanford for a pediatric endocrine fellowship and the rest, as they say, is history. Ron trained with Ray Hintz and was awarded the Basil O’Connor and Mellon Foundation Fellowships and studied IGFs and IGFBPs and rapidly became the world’s authority on these topics as well as establishing himself as the foremost growth expert in the pediatric endocrine field. Among his many scientific achievements are the delineation of multiple defects in the GH-signaling cascade as well as characterization of the mechanisms of action of IGFBPs and related proteins. While doing so, Ron has also served for nearly a decade as a remarkably successful chair of Pediatrics at Portland in the Oregon Heath Sciences University, which he has transformed into one of the top departments in the Nation, and recently as the Senior Vice-President for Medical Affairs of the Lucile Packard Foundation for Children’s Health at Stanford University. Dr. Rosenfeld’s many other accolades include the 2007 Transatlantic Medal from The Society for Endocrinology, the 2007 Maureen Andrew Mentor Award, Society of Pediatric Research and Academic Pediatric Societies, the 2005 Joseph St. Geme Education Award, Society for Pediatric Research, the Clinical Endocrinology Trust Medal, the presidencies of the Lawson Wilkins Pediatric Endocrine Societies and the Western Society of Pediatric Research, the Ross Award in Research from the Society for Pediatric Research, the Henry J. Kaiser Award for Excellence in Teaching, Stanford University School of Medicine. Dr. Ron Rosenfeld joins a select group of pediatric endocrinologists to win this prestigious award, including Del Fisher (1998), Bob Blizzard (1994), Claude Migeon (1992), Maria New (1988) and Mel Grumbach (1980). Like each of these individuals, Ron distinguished himself as a unique contributor to his field, performing work that has transformed not just pediatrics, but endocrinology in general.
As evident from his many teaching awards, Dr. Rosenfeld has been a remarkably successful and sought after mentor and he trained dozens of fellows. Many of these are now leaders in pediatric endocrinology in the United States, Japan, and Europe. Dr. Rosenfeld published over 600 papers, chapters and reviews, has served on the editorial boards of every major endocrine journal and has participated in organizing scores of meetings.
Dr. Rosenfeld, an inspiring human being, is a man of the highest integrity and empathy for his patients, fellows, friends and colleagues. He marriage of nearly four decades to his wife Val, their children Lauren and Jeff and their two grandchildren, his love of golf, and his passion for art and collecting photographs, rare books and other unique objects round off this remarkable person.
Dr. Rosenfeld is most worthy of the Robert H. Williams Distinguished Leadership Award of The Endocrine Society.
Pinchas Cohen
Citation for the 2008 Edwin B. Astwood Award Lecture of The Endocrine Society to Dr. John A. Cidlowski
Dr. John A. Cidlowski is a senior investigator at the NIH (NIEHS) and is the Chief of the Laboratory of Signal Transduction. Within that laboratory he heads the Molecular Endocrinology Section that focuses its research on glucocorticoid action and mechanisms of apoptosis. His discoveries in both of these scientific arenas have led to new insights into the mechanisms of glucocorticoid action and the role of apoptosis in human health and disease.
Dr. Cidlowski began his scientific career by obtaining a Ph.D. in Endocrinology in 1975 from the Medical College of Georgia where he worked with the late Thomas G. Muldoon studying mechanisms regulating estrogen receptor biosynthesis and degradation. His devotion to the study of glucocorticoids developed during his USPHS postdoctoral fellowship at Dartmouth Medical School with Dr. Allan Munck. Here he independently discovered that glucocorticoid receptors are regulated during the cell cycle, and also laid the groundwork for understanding how glucocorticoids kill lymphocytes. Following two years at Dartmouth he began his independent career as an Assistant Professor of Biochemistry at the University of Vermont, School of Medicine, where he and his colleagues first demonstrated that proteolysis is a fundamental component of lymphocyte apoptosis and provided the first direct evidence for post transcriptional modification of glucocorticoid receptors. His research group also discovered that the glucocorticoid receptor is down-regulated by ligand, a clinically relevant component of steroid hormone resistance.
In 1982 Dr. Cidlowski joined the faculty at the University of North Carolina at Chapel Hill where he continued studies on glucocorticoid receptors and apoptosis. At North Carolina, his laboratory first established the use of flow cytometry as a tool for the study of apoptosis, and discovered the nuclease known to cause the initial breaks in DNA during glucocorticoid induced apoptosis. His laboratory also defined the mutual antagonism that exists between the steroid receptors and NF κB. He also developed antibodies to the glucocorticoid receptor that continue to be used world wide.
In 1995 Dr. Cidlowski and his research group were recruited to NIH (NIEHS) to establish a presence in apoptosis and glucocorticoid receptor mechanisms. His research at NIEHS has provided new insights in both scientific areas, including the establishment of a regulatory role for ion channels in lymphocyte apoptosis, the identification of hGRβ as a bona fide mediator of glucocorticoid resistance in human inflammatory disease and a function for the proteosome in the degradation of the glucocorticoid receptor and the termination of glucocorticoid signals. He and his colleagues have also defined an unprecedented role for glucocorticoids in stimulating components of the innate immune system. Most recently, he has demonstrated the presence of tissue-specific isoforms of the glucocorticoid receptor that are produced via alternative translation initiation which likely contribute to the diversity of actions of glucocorticoids in man. To date his laboratory has published more than 260 scholarly articles, two of which have been awarded “Paper of the Year” at NIH (NIEHS).
Clearly, Dr. Cidlowski and his colleagues have made unique and important contributions that have advanced significantly our knowledge of both glucocorticoid action and apoptosis. In addition to his scientific contributions, Dr. Cidlowski has impacted the field of Endocrinology through his service to the discipline. He has been a member of the Endocrine Society since 1977, and has served with distinction as a member or chair of study sections for the NIH and U.S. Army. As a member of the Keystone Scientific Advisory Board, he established the first Keystone Conferences on nuclear receptors and apoptosis. He has served on the editorial boards of Endocrinology, The Journal of Steroid Biochemistry and Molecular Biology, and as Editor of Endocrine Reviews, Molecular Endocrinology and Steroids. Dr. Cidlowski is currently Editor in Chief of Molecular Endocrinology.
Throughout his career, Dr. Cidlowski has also taken a keen interest in nurturing the development of young scientists via training of graduate students, medical students, and postdoctoral fellows in the discipline of Endocrinology. To date he has fostered the careers of 58 fellows many of whom have successful independent careers and are Endocrine Society members. Dr. Cidlowski has given over 200 major lectures and has been the recipient of numerous scientific awards, including the Philip Hench Nobel Memorial Lecture.
In summary, it is clear that Dr. Cidlowski is a highly distinguished scientist who has made many important and valuable contributions to the field of Endocrinology. His work reflects the stature and purpose of the Edwin B. Astwood award of the Endocrine Society.
Kathryn B. Horwitz
Citation for the 2008 Clinical Investigator Award Lecture of The Endocrine Society to Dr. John C. Marshall
Translational research has become the scientific buzzword of the new millennium, but its exact nature remains elusive. Indeed, I think that many of us will agree that, to paraphrase Justice Potter Stewart, we cannot define it but we know it when we see it. Fortunately, John Marshall’s accomplishments provide a consummate illustration of translational research.
John was born in Blackburn, Lancashire, England. He obtained his medical training at the Victoria University of Manchester and his endocrinology at the Hammersmith Hospital in London and at UCLA-Harbor General Hospital. He has spent the majority of his academic career in the US, first at the University of Michigan and now at the University of Virginia where he is the Andrew D. Hart Professor of Internal Medicine and Director of the Center for Research in Reproduction.
Although his early research was in cardiology, he quickly saw the light and turned his attention to reproductive endocrinology. And what a light that was in the early 70s - it was the dawn of a new era with the recent discovery of gonadotropin releasing hormone (GnRH) and pulsatile LH secretion. John was among the first investigators to use these discoveries as powerful tools to unravel the complex regulation of human reproductive function. By the end of the decade, he had shown for the first time in humans that a fixed pattern of pulsatile GnRH release could produce a differential pattern of LH and FSH release due to changes in pituitary sensitivity. He proceeded to define the contributions of sex hormone feedback to the regulation of gonadotropin secretion in men as well as women. These studies suggested a key role for endogenous opiates as mediators of sex hormone feedback. From these studies, John was able to provide a cogent model for human puberty initiated solely by changes in GnRH pulsatility.
In a bedside-to-bench approach that has characterized his career, John used complementary animal and in vitro studies to investigate the cellular and molecular mechanisms of these physiologic insights. A central question in the field was how a single cell type, the gonadotrope, could simultaneously secrete varying amounts of each gonadotropin. John discovered that GnRH pulse frequency differentially regulates LH and FSH gene transcription. This finding was not only a major milestone in neuroendocrinology but also had broad scientific implications by providing an important molecular mechanism for pulsatile hormone action. He has gone on to elucidate the intracellular signaling pathways mediating these GnRH actions.
The logical progression of his research on human reproductive neuroendocrinology were studies investigating the pathogenesis of disordered gonadotropin in the common but poorly understood disorder, polycystic ovary syndrome (PCOS). Although a cardinal feature of PCOS was hyperandrogenemia, it was thought that the aromatization of androgen to estrogen altered gonadotropin secretion in the syndrome. In a series of highly innovative human studies, John first identified a novel neuroendocrine abnormality in PCOS - decreased sensitivity to the feedback of effects of estradiol and progesterone to slow the GnRH pulse generator. Further, the pure androgen receptor antagonist, flutamide, could normalize sensitivity to feedback. This landmark study demonstrated for the first time that androgens could directly alter gonadotropin secretion in PCOS. John then provided new insights into the developmental origins of PCOS by demonstrating that prepubertal obese girls have elevated androgen levels. These remarkable studies have led to a complete paradigm shift in our understanding of the etiology of the disorder. They suggest that hyperandrogenemia, perhaps as a consequence of obesity, is an early and, potentially, primary defect in the pathogenesis of PCOS.
In summary, John Marshall has made seminal scientific contributions that have resulted in quantum advances in our understanding of reproductive biology. He is the quintessential clinical investigator who has truly translated physiologic observations into powerful mechanistic insights through complementary human and basic studies. His extensive and extraordinary accomplishments clearly merit the Endocrine Society’s highest recognition for outstanding achievement in the field, the Clinical Investigator Award.
Andrea E. Dunaif
Citation for the 2008 Gerald D. Aurbach Award Lecture of The Endocrine Society to Dr. Andrew F. Stewart
Dr. Andrew Fyfe Stewart was born New York City in 1948. He graduated from Trinity College in Hartford CT in 1970 and Columbia University College of Physicians and Surgeons in 1974. He was a medical resident at Roosevelt Hospital in New York City and then served as a rural general practitioner on Fishers Island, off the coast of Connecticut.
He epitomizes the translational investigator, equally comfortable at the bench and the bedside. His academic career began in 1978 when he entered the Endocrinology Fellowship Training Program at Yale University, working under the outstanding mentorship and inspiration of two leaders in bone and mineral metabolism, Drs. Arthur Eastwood Broadus and Howard Rasmussen. Under the direct supervision of Dr. Broadus, Dr. Stewart was the first to characterize in complete biochemical detail the common paraneoplastic syndrome, humoral hypercalcemia of malignancy, or HHM, which he and Dr. Broadus so named. These clinical studies led Dr. Stewart into the laboratory, where he purified and sequenced parathyroid hormone-related protein, or PTHrP. The Yale group cloned the PTHrP cDNA, and Stewart and his colleagues went on to fulfill Koch’s postulates, demonstrating that PTHrP is present in tumors from patients with HHM, in the circulation of patients with HHM, and that the syndrome can be reproduced in animals and humans by PTHrP infusion. They also showed that PTHrP is produced ubiquitously and has critical normal functions in a broad variety of tissues and organs.
Dr. Stewart left Yale in 1997 to become the Chief of the Division of Endocrinology at the University of Pittsburgh, where he has built one of the strongest research and clinical endocrinology divisions in the US. His research focuses on the normal physiology and therapeutic applications of PTHrP. Building on the animal work from the laboratories of Drs. John Wysolmerski and Christopher Kovacs, he and Dr. Mara Horwitz employed PTHrP in an infusion model in human volunteers that mimics the physiological bone loss surrounding human lactation. He and Dr. Horwitz have also demonstrated that PTHrP has remarkable therapeutic effects in humans as a pure skeletal anabolic agent for the treatment of postmenopausal osteoporosis. He and Drs. Rupangi C. Vasavada and Adolfo Garcia-Ocaña demonstrated for the first time in vivo that PTHrP and other growth factors such as hepatocyte growth factor and placental lactogen can increase both pancreatic beta cell mass as well as islet function, and hold promise for the treatment of diabetes. These growth factors also enhance the replication and function of rodent and primate islets transplanted into diabetic models. His ability to move between the basic and clinical arenas has led to his current leadership in the nascent field of pancreatic cell cycle control as therapeutic approaches to Types 1 and 2 diabetes. Finally, working with Dr. Nathalie Fiaschi-Taesch, he has shown that PTHrP in the arterial smooth muscle cell is essential for normal arterial smooth muscle development and contributes importantly to arterial re-stenosis following angioplasty. He and Dr. Fiasch-Taesch have also demonstrated that arterial re-stenosis can be entirely prevented in vivo using mutant PTHrP constructs, suggesting therapeutic options for PTHrP in atherosclerotic disease.
Dr. Stewart’s 200 publications have appeared in journals of the highest quality, including Science, the New England Journal of Medicine, the Proceedings of the National Academy of Sciences, the Journal of Clinical Endocrinology and Metabolism, Circulation, and Diabetes. He has received continuous support for his work from the NIH/NIDDK and the American Diabetes Association. He is an international authority in disorders of bone and mineral metabolism and has written chapters in this area in leading textbooks of medicine and endocrinology. Dr. Stewart is an outstanding teacher, both in small groups and on the podium. He is a regular speaker at invited symposia at the Endocrine Society, the American Society for Bone and Mineral Research, and the American Diabetes Association. He has also mentored some 50 trainees. He attributes his skill as a mentor directly to his own mentoring by Drs. Broadus and Rasmussen. He is regularly cited in the Best Physicians in the US, and has won numerous awards for his research. He has Chaired the Annual Meeting of the Endocrine Society, and currently serves at the Secretary-Treasurer of the Endocrine Society. He is a member of the American Society for Clinical Investigation and the Association of American Physicians. He has been supported in all of his work by his wife of 39 years, Lindsay Clark Stewart.
Arthur E. Broadus
Citation for the 2008 Sidney H. Ingbar Distinguished Service Award of The Endocrine Society to Dr. Lisa H. Fish
As the recipient of the 2008 Sidney H. Ingbar Award, Lisa H. Fish, MD, FACP, joins an impressive cadre of individuals who are united by their records of service to the field of endocrinology. Dr. Fish received her undergraduate and medical training at Brown University in Providence, Rhode Island. She completed her Internal Medicine Residency and Endocrine Fellowship at the University of Minnesota Hospitals and then spent a year as an Instructor and Research Fellow in Diabetes at the University of California at San Diego. She returned to Minnesota as an Assistant Professor at the University of Minnesota and St. Paul Ramsey Medical Center. In 1991 she moved to Park Nicollet Medical Center, also affiliated, with the University of Minnesota, where she is currently Assistant Clinical Professor, Chair of Endocrinology and Medical Director of the Diabetes in Pregnancy Program. She is also PI and Medical Director of Inpatient Diabetes and the Diabetes Intensification Program of the International Diabetes Center.
Dr. Fish is the consummate clinical endocrinologist, spending over 75% of her time seeing patients. Her interests and expertise include not only diabetes, but also osteoporosis, thyroid and adrenal disease in pregnancy and hormone abuse. Her emphasis on a ‘partnership of care’ is a very powerful motivator for patients. She has been widely recognized for her clinical excellence and among other tributes, received the Distinguished Physician Award from the Endocrine Society in 2002.
In addition to her clinical contributions as a practicing Endocrinologist, Dr. Fish has been extremely active in the professional societies that support our subspecialty. She has clearly helped to define the role of the Physician in Practice as an active contributor and leader in the Endocrine Society by committing her energy, expertise and leadership to such Society activities as the Media Relations, Government Relations, Long Range Planning, Clinical Initiatives and Nominating Committees and as a member of Council. She was the first Endocrine Society member seated in the American Medical Association (AMA) House of Delegates. In 1997 she received an Endocrine Society Presidential Citation for Leadership in Clinical Endocrinology for her work in bringing the Endocrine Society to the AMA. It is only through such active representation on the influential AMA, that Endocrinologists will be recognized for the specialized expertise they bring to their patients.
Dr. Fish has also contributed significantly to the Hormone Foundation, the public education arm of The Endocrine Society as a member of its Board from 1997–2004 and Chair of the Hormone Abuse Project. In 2005 she became the first Chair of the Hormone Foundation Committee whose formation resulted from a restructuring that forged closer ties with the strategic aims of the Endocrine Society. The overall mission of the Hormone Foundation is to be a leading source of hormone-realted health information for the public, physicians, allied health professionals and the media and Dr. Fish’s contributions to this goal cannot be overestimated. In this regard, she is justifiably most proud of the outstanding bilingual fact sheets that are published in Spanish, English and now several other languages in the Journal of Clinical Endocrinology & Metabolism and on the Endocrine Sociey website and of the patient information summaries that have been coordinated with the Endocrine Society’s Clinical Guidelines. These patient summaries serve to amplify the impact of the thoughful and comprehensive analysis that goes into the formulation of these Clinical Guidelines. This year, Dr. Fish has taken on a new role in the Endocrine Society, as Vice President (Physician in Practice). She has once again shown her leadership abilities with her commitment to championing the issues relevant to clinicians in a way that furthers the tripartite nature of our society.
In short, Dr. Fish has made enormous contributions to the Endocrine Society. Her commitment to issues of relevance to the practicing physician has increased the public profile not only of the Endocrine Society, but also of the field of Endocrinology. She has a deep-seated appreciation for the interrelated contributions of basic and clinical scientists and physicians in practice to the Society and has repeatedly demonstrated her abilities as a powerful leader in our society. I can think of no more deserving recipient of the 2008 Sidney H. Ingbar Distinguished Service Award than Lisa Fish.
Janet E. Hall
Citation for the 2008 Roy O. Greep Award Lecture of The Endocrine Society to Dr. Nancy Lynn Weigel
Dr. Nancy L. Weigel is the recipient of the 2008 Roy O. Greep Award Lecture, given in recognition of her extensive contributions to understanding the role of cell signaling in steroid hormone action. Nancy Weigel received her B.A. in chemistry and anthropology from Cornell University and her M.A. and Ph.D. from Johns Hopkins University for studies of the bacterial phosphotransferase system with Dr. Saul Roseman. She did her post-doctoral training with Drs. William Schrader and Bert O’Malley at Baylor College of Medicine studying the structure and function of the chicken progesterone receptor. She subsequently joined the faculty of the Cell Biology Department at Baylor College of Medicine and is currently Professor of Molecular and Cellular Biology at Baylor College of Medicine.
Dr. Weigel’s work has focused on the role of cell signaling in steroid receptor action and on the activities of nuclear hormone receptors in prostate cancer. She was the first to identify phosphorylation sites in a steroid receptor, the chicken progesterone receptor, and subsequently identified the many sites in the human progesterone receptor, in other nuclear receptors and the p160 coactivator, SRC-1. She participated in the first demonstration of hormone independent activation of steroid receptors, cAMP induced activation of the chicken progesterone receptor. She subsequently showed that this activation was independent of changes in receptor phosphorylation, but that phosphorylation of SRC-1 was altered through cAMP dependent activation of p42/p44 MAPK. The activation of steroid receptors in the absence of hormone is receptor and pathway specific and later gained great clinical relevance when the high frequency of ‘ligand-independent’ endocrine cancers was appreciated. Although the human progesterone receptor is not activated by cAMP treatment alone, cAMP causes the progesterone receptor antagonist, RU486, to act as a progesterone receptor agonist. Dr. Weigel also was the first to show that human progesterone receptor activity is cell cycle dependent with a peak transcriptional activity in S phase. In studying the role of cell signaling in human progesterone receptor function, she found that cyclin A2 in combination with its cyclin dependent kinase partner functions as a progesterone receptor coactivator and that cyclin dependent kinase activity is required for recruitment of SRC-1 coactivator and progesterone receptor function.
Another of her major research interests is steroid receptor action in prostate cancer. She found that the protein kinase-A activator, forskolin, can activate the androgen receptor in the absence of hormone. The finding that activators of cell signaling pathways can activate androgen receptor suggested that “androgen independent” prostate cancer cells may remain androgen receptor dependent. Using the C4–2 prostate cancer cell line that grows in androgen depleted medium and expresses the androgen regulated gene, PSA (prostate specific antigen), she showed that depleting androgen receptor using siRNA eliminated both cell proliferation and PSA expression.
Induction of PSA is typically utilized as a surrogate for androgen receptor action, but Dr. Weigel has shown that p160 coactivators and cell signaling requirements for androgen receptor action are target gene specific since SRC-1, but not TIF2, was required for androgen dependent repression of maspin expression. This was one of the first demonstrations that SRC-1 potentiated repression as well as activation. Dr. Weigel has also studied vitamin D action in prostate cancer; she has identified many targets of vitamin D action and was the first to show that a synthetic analog of the active metabolite of vitamin D inhibited the growth of subcutaneous prostate cancer xenografts without causing hypercalcemia.
Nancy Weigel is known widely as a critical and pioneering scientist in her field of hormone action. She participated and chaired many review panels, organized national/international meetings, has been a member of many journal editorial boards, and participated widely in positions in The Endocrine Society and Women in Endocrinology. She is a Searle scholar, as well as an outstanding teacher who won the Marc Dresden Award for teaching. As a valued senior Professor at Baylor College of Medicine, she represents an ideal role model for the 2008 Roy O. Greep Award Lecture.
Bert W. O'Malley
Citation for the 2008 Distinguished Educator Award of The Endocrine Society to Dr. Ronald S. Swerdloff
Dr. Ronald S. Swerdloff is this year’s recipient of the Endocrine Society’s Distinguished Educator Award for his exceptional talents in the communication of fundamental and clinical knowledge and for his overall career achievements. Swerdloff benefited substantially from his superb early clinical and research training. He obtained his medical degree from the University of California at San Francisco, initiated Internal Medicine residency at the University of Washington, and then became a Clinical Associate at the National Institute of Aging. While there, he worked with Dr. Rubin Andres and studied carbohydrate metabolism in aging man. Completing his residency in Internal Medicine at UCLA, he spent an additional two years of endocrinology training at the Harbor-UCLA Medical Center with his second mentor, Dr. William D Odell. This was a time of a great explosion of knowledge in the area of reproductive endocrinology. Dr. Swerdloff capitalized on this by polishing his clinical and research skills and making many important scientific observations. Thereafter he joined the faculty at the Harbor-UCLA campus and was named Division Chief at age 35, serving as leader of this highly productive program since that time.
Dr. Swerdloff has received numerous previous awards including the American Society of Andrology Distinguished Andrologist Award, The Most Outstanding Faculty Award at UCLA, and the Outstanding West Coast Investigator by the Western Society of Clinical Investigation. Dr. Swerdloff has performed leadership roles for many regional and national societies including the American Society of Andrology (President) and the Endocrine Society (Associate Editor, JCEM).He was a long time member of the Methods for Regulation of Fertility task force of the World Health Organization and has served as advisor to China and India to oversee the development of specialized research centers on male contraception. He has served as the Director of the UCLA Population Research Center, UCLA World Health Organization Collaborating Center for Research in Human Reproduction, Mellon Center for Men’s Health and NIH Contraceptive Clinical Trials Center.
While Dr. Swerdloff has exhibited multi-faceted talents in several aspects of academic medicine, this current award recognizes his dedication to, and excellence in education. Dr. Swerdloff has directed the clinical and research training programs at Harbor-UCLA for 35 years and has trained over 130 endocrine fellows. A number of trainees have gone on to professorships and Chairmanships of their own and are leaders in endocrinology, metabolism, andrology, clinical nutrition and diabetes. He has also trained subspecialty fellows in the allied disciplines, urology and gynecology. As a direct reflection of his talents in mentorship, collaborative research, and leadership, Dr. Swerdloff has effectively organized research teams that published more than 300 peer reviewed articles in his field. With the depth of knowledge gained from this work, he has written numerous reviews and over 100 book chapters.
Effectiveness as an educator requires both in depth understanding of one’s field and highly polished communication skills. Dr. Swerdloff has gained an extensive knowledge base through his broadly based academic pursuits. He is both a basic scientist as well as translational and clinical investigator. His contributions in the areas of regulation of spermatogenesis, hypothalamic pituitary physiology, pathophysiology and treatment of male hypogonadism and pioneering work in the areas of male contraceptive development clearly define why he is a highly respected scientist. Moreover, he has an innate ability to clearly identify critical issues, articulate their essence, and focus his assessment and conclusions on the most important components. Because of his scientific reputation, he has been asked to serve on, and chair many guideline committees for societies in a number of disciplines. He is a frequent plenary speaker at scientific and clinical meetings worldwide. Close observation of his clinical teaching on endocrinology rounds reveals that he makes insightful observations and concise judgments and can communicate these to trainees in an exciting and instructive manner.
Rare is the medical leader today with three or more legs of the proverbial academic stool. Dr. Swerdloff, after 45 years as a physician, is able to manage his administrative responsibilities, research investigations, teaching of students, residents and fellows as well as serving as an attending physician in general internal medicine and endocrinology. He takes Among these many activities, he takes particular pride in the accomplishments of his trainees and his role as an educator and patient advocate.
In summary, Dr. Swerdloff is a highly accomplished educator, scientist, administrator and clinician. His educational leadership has created a legacy of outstanding trainees who have followed his example as a role model and added their own outstanding contributions to the field of reproductive endocrinology. Dr. Swerdloff points to the wonderful mentorship he received from Dr. Rubin Andres and Dr. William D. Odell and particularly prizes the shared experiences and major contributions made by his colleagues and trainees. As he will often state, Dr. Swerdloff gives particular credit to his research collaborator, highly successful scientist and wife, Dr. Christina Wang.
Richard J. Santen
Citation for the 2008 Distinguished Physician Award of The Endocrine Society to Dr. F. John Service
F. John Service was born in Kapuskasing (population 507), in northern Ontario, Canada, in 1936. From the age of 5 years he lived with his family in the southern part of the province until heading off to college. After receiving a Bachelor of Arts degree from McMaster University, he attended McGill University Medical School and subsequently earned his Ph.D. degree in Medicine at the University of Minnesota. He completed his fellowship in internal medicine and “apprenticeship” in endocrinology at Mayo Clinic in Rochester, Minnesota, in 1969 and was immediately recruited to the staff at that institution—a position he continues in to this day. He was advanced to the position of Professor of Medicine in the Mayo Clinic College of Medicine in 1982. At Mayo Clinic, many long-standing clinicians are known simply by their initials—thus, John is fondly referred to as FJS.
Although FJS has had National Institutes of Health grant support since 1978, most of his time at Mayo Clinic Rochester has been in the role of a clinician. He was named the Earl and Annette R. McDonough Professor in 1999 at Mayo Clinic Rochester. He is the consummate academic physician who has successfully balanced patient care, teaching, and research. Serving as a mentor and role model, FJS has taught medical students, residents, fellows, and practicing physicians the art and science of endocrinology.
During his 40 years at Mayo Clinic Rochester, he has made major contributions to the fields of diabetes and hypoglycemic disorders. As a result of his pioneering work using continuous blood glucose analysis in type 1 and type 2 diabetes mellitus in the late 1960s, modernization of treatment using intensive insulin therapy ultimately became possible. FJS is an internationally recognized expert in diabetes mellitus and hypoglycemia. Colleagues throughout the world seek his opinion on the diagnostic evaluation and treatment of patients with hypoglycemia. FJS has more 200 publications, and he has participated in more than 50 invited national and international symposia.
Despite his prolific career in clinical research, FJS is most known for his abilities in the clinic—he is indeed a “doctor’s doctor.” His clinical acumen in the management of hypoglycemic disorders is unparalleled. He also excels in professional interactions with his colleagues at Mayo Clinic and throughout the world and has earned the respect of all who have been fortunate to work with him. He has passed the most critical test for acceptance as an outstanding clinician—recognition by endocrine fellows at his institution that he is the best in the world at what he does.
FJS brings a unique approach to everything he accomplishes. In his 5-year tenure as Editor-in-Chief of Endocrine Practice, he authored 30 editorials on topics that ranged from the appropriate use of the English language to documenting the behavior of the dung beetle. He frequently resorted to a self-bestowed license for metaphoric indulgence: “In our role as therapeutic ‘travel agents,’ we physicians have the task, which I fear only some of us recognize as daunting, to identify the best route for each individual traveler.”(1) A stickler for the proper use of the English language, in one of his editorials, FJS commented: “Besides grammatical errors, the language is polluted (even by the ‘educated’) with jargon, clichés, and what I will call administrationese. I cannot count the times I have recently heard ‘going forward.’ ‘In the future’ would have been more suitable, thank you. Departments and institutions do not go forward; only movable objects have this capability. The last time I checked, my institution had the same address as it had previously.”(2)
In summary, for his outstanding contributions and shining example across the areas of patient care, diagnostic evaluation of the hypoglycemic patient, education, clinical research, and the proper use of the English language in medicine, The Endocrine Society honors Dr. F. John Service with the 2008 Distinguished Physician Award.
William F. Young, Jr.
Citation for the 2008 Richard E. Weitzman Memorial Award of The Endocrine Society to Dr. Tannishtha Reya
Dr. Tannishtha Reya has made seminal contributions towards understanding how signal transduction cascades regulate hematopoeitic stem cell growth, maintenance, commitment and self-renewal. Already, in just five short years as an independent investigator, Dr. Reya’s body of work has provided significant implications for medicine as well as fundamental advances concerning the molecular pathways that regulate the biology of stem cells. In her first publication as a Duke faculty member Dr. Reya reported in a 2003 issue of Nature that the signaling cascade initiated by the Wnt 3A growth factor controls the proliferation of hematopoetic stem cells (HSCs) and showed that expression of an activated form of β-catenin allowed expansion of these stem cells in vitro in a manner that allows maintenance of their pluripotent potential when introduced into immunocompromised mice. This fundamental advance in promoting stem cell self-renewal was heralded in independent editorials published in Nature, Science, The Lancet and Nature Reviews Molecular Cell Biology. This unprecedented attention to this work introduced Dr. Reya to the international scientific community and launched her independent career in a most spectacular fashion.
Unfazed by this amazing initial success, Dr. Reya continued to investigate the fundamental question in hematopoietic stem cell (HSC) biology of how self-renewal is controlled and maintained. Her second independent paper was published in Nature Immunology in 2005 and showed that Notch and Wnt3A signaling are required in complementary roles by HSCs to maintain their undifferentiated state. In this paper Dr. Reya uncovered the molecular basis for the cross-talk between the Notch and Wnt signaling pathways in the maintenance of HSC self-renewal. These studies began with her observation that Wnt signaling upregulated Notch1. Tannishtha then used a Notch reporter mouse to show that the activity of the Notch pathway is highly activated in HSCs and that it is downregulated as HSCs undergo differentiation. Using innovative approaches, she showed that inhibition of Notch signaling results in accelerated differentiation of HSCs in vitro and depletion of HSCs in vivo. Most importantly she showed that Notch signaling is required for Wnt-mediated maintenance of undifferentiated HSCs, but is dispensable for HSC survival and entry into the cell cycle. As the hematopoietic microenvironment is critical for regulation of the number of HSCs, Dr. Reya searched for secreted molecules that may mediate cell proliferation and identified adiponectin in the process. In a paper published in J. Immunol. in 2007, she reported that HSCs express adiponectin receptors and that the hormone increases HSC proliferation via activation of the p38 MAPK pathway while retaining the cells in a functionally immature state. Collectively, these observations provide molecular insight into the signaling cascades that regulate HSC maintenance, proliferation, survival and differentiation. One incredibly important remaining question is the mechanism that determines whether an HSC will divide symmetrically to self-renew or asymmetrically to provide progenitor cells capable of producing blood.
To address the issue of symmetric vs. asymmetric division, Dr. Reya applied innovative technology to the problem. She used time-lapse microscopy together with a clever genetic screen to evaluate sequential divisions of hematopoietic stem cells and the retention of stem cell properties and published this work in Cell Stem Cell in 2007. Using a Notch reporter mouse in which expression of green fluorescence protein functions as a sensor for differentiation, Dr. Reya revealed that the balance between symmetric and asymmetric HSC divisions is not hard-wired but rather is responsive to both extrinsic and intrinsic cues. She made the critical observation that a pro-differentiation microenvironment promotes asymmetric cell division, whereas a pro-renewal environment promotes symmetric cell division. Notably, Dr. Reya also found that expression of distinct types of oncoproteins differentially affect this process. Expression of the oncogenic Bcr-Abl tyrosine kinase primarily affects the rate of cell division and death, whereas expression of the Nup98-HoxA9 oncoprotein promotes symmetric cell division. Thus, some oncogenes may subvert the balance between symmetric and asymmetric cell division. This work will serve as the foundation for future pioneering studies to visualize HSC signaling and behavior in vivo and examine the effect of aberrant microenvironments and various oncogenes on this process. In addition to showing that oncogenes can subvert normal mechanisms of asymmetric division, Dr. Reya’s work, published in Cancer Cell in 2007, has also shown that oncogenes can subvert and become dependant on normal developmental pathways such as Wnt signaling.
In summary, Dr. Reya has made amazing progress in her quest to understand how stem cells are controlled by extrinsic and intrinsic signaling pathways at a very early stage in her career. Her insight into how hormones and growth factors control the asymmetric division of stem cells is fundamental to both stem cell and cancer biology. Her star is in ascension and will continue to rise for many years to come. Tannishtha Reya is highly deserving of the Endocrine Society’s Richard E. Weitzman Memorial Award.
Anthony R. Means
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