Speaker Biographies from the Neural Control of Appetite Lablinks Meeting

Thank you for attending the Neural Control of Appetite, a Cell Press LabLinks meeting, on Tuesday, May 7, 2013. Please see the full list of speaker biographies below.

Ronald Lechan, MD, PhD Professor of Medicine, Sackler School, Tufts University

Synopsis The anatomy and physiology of thyrotropin-releasing hormone (TRH)-synthesizing neurons in the hypothalamic paraventricular nucleus (PVN) is the focus of our research. We study (1) the choroid plexis and cerebral spinal fluid in the transport of T4 into the brain; (2) the effect of type 2 deiodinase in ependymal cells (tanycytes) on feedback inhibition of thyroid hormone on hypophysiotropic TRH neurons in the PVN; (3) leptin-mediated paradoxic reduction in the biosynthesis of TRH in the PVN during fasting; and (4) the anatomical characterization, nuclear and cytoplasmic distribution, and potential interaction of thyroid hormone receptors in thyroid-hormone-responsive and -unresponsive TRH neurons in the brain and their response to hormonal manipulation.

Bradford Lowell, MD, PhD Professor of Medicine, Endocrine Division, Beth Israel Deaconess Medical Center and Neuroscience Faculty,

Synopsis We utilize genetic engineering, in conjunction with electrophysiology, optogenetics, pharmacogenetics, and rabies mapping, to elucidate central neurocircuits controlling feeding behavior, body-weight homeostasis, and fuel metabolism in mice. Specifically, transgenic, knockout, knockin, and Cre-dependent AAV viral approaches (for delivery of optogenetic, DREADD, and monosynaptic rabies reagents) are used in the manipulation and mapping of neuronal circuits. The goal of these studies is to link neurobiologic processes within defined sets of neurons with specific behaviors and physiologic responses. The ultimate goal is to mechanistically understand the “neurocircuit basis” for regulation of food intake, energy expenditure, and glucose homeostasis. Given our expertise in gene knockout and transgenic technology, we can efficiently and rapidly create numerous lines of genetically engineered mice, important examples of which are neuron-specific ires-Cre knockin mice, which enable Cre-dependent AAV technology. This allows us to bring novel, powerful approaches to bear on the neural circuits underlying behavior and metabolism. Our combined use of mouse genetic engineering, brain- slice electrophysiology, and whole-animal physiology is ideally suited to the study of these problems.

Umut Ozcan, MD Associate Professor, Children's Hospital and Harvard Medical School

Synopsis Dr. Umut Ozcan is an Associate Professor in the Division of Endocrinology at Boston Children's Hospital and Harvard Medical School. He has completed his research training at the Joslin Center and the Harvard School of Public Health. The primary aim of the Ozcan laboratory is to delineate the molecular mechanisms of endoplasmic reticulum (ER)-stress-originated pathologies in obesity. The two main focus areas are and leptin receptor signaling and their crosstalk with the unfolded protein response (UPR) pathway. Dr. Ozcan's group employs a multidisciplinary approach that draws on mouse genetics, ER physiology and pathophysiology, biochemistry, chemical biology, and proteomics to identify key metabolic pathways that determine the cell’s response to physiologic and pathophysiologic ER stress. The ultimate goal of this integrated approach is to unravel the potential therapeutic targets in the UPR pathway in order to reduce ER stress in obesity and find a cure for obesity and obesity-related diseases. The Ozcan group has made seminal discoveries in these areas and is currently also working on potent drugs that could be future treatments for obesity and type 2 diabetes.

Maribel Rios, PhD Associate Professor, Department of Neuroscience, Tufts University School of Medicine

Synopsis Our laboratory uses molecular, biochemical, electrophysiological, behavioral, and genetic tools to ascertain the role of brain-derived neurotrophic factor (BDNF) in the modulation of energy homeostasis and affective behavior. For this, we generate and study mice with central or site-specific deletion of BDNF. Our efforts are focused on defining brain neural circuits for which modulation by BDNF controls appetite and affective states and identifying the cellular and molecular mechanisms underlying the actions of this neurotrophin.

Gorica Petrovich, PhD Associate Professor, Department of Psychology, Boston College

Synopsis Gorica Petrovich is an associate professor in the Department of Psychology at Boston College. She received a BS from the School of Natural Sciences and Mathematics at the University of Belgrade in 1989. Under the mentorship of Larry Swanson, she earned her doctorate in Neurobiology from the University of Southern California in 1997. Her PhD thesis work used neuroanatomical methods to define emotion- and motivation-critical connections of the amygdala and the associated brain network. Her postdoctoral fellowship was in the field of behavioral neuroscience under the guidance of Michela Gallagher in the Department of Psychological and Brain Sciences at The Johns Hopkins University. There, Petrovich began to examine the role of the environment in the control of feeding and the underlying brain substrates. Her current research program continues to investigate the motivation to eat and how it can be controlled by environmental cues. She uses rodent models to study how basic hunger mechanisms can be modulated by learning and stress and to study the underlying brain mechanisms and plasticity. Her work in animals is informative for understanding the control of appetite and eating in humans and maladaptive environmental influences that could lead to eating disorders. The NIH and NIDDK have funded her current and past research.

Jeffrey Friedman, MD, PhD Investigator, Howard Hughes Medical Institute Marilyn M. Simpson Professor Laboratory of Molecular Genetics The Rockefeller University

Synopsis Dr. Jeffrey Friedman is a physician scientist studying the genetic mechanisms that regulate body weight. Dr. Friedman's research on various aspects of obesity received national attention in late 1994, when it was announced that he and his colleagues had isolated the mouse ob gene and its human homologue. They subsequently found that injections of the encoded protein, leptin, decreases body weight of mice by reducing food intake and increasing energy expenditure. Current research is aimed at understanding the genetic basis of obesity in humans and the mechanisms by which leptin transmits its weight-reducing signal. He is currently a professor at The Rockefeller University and an investigator for the Howard Hughes Medical Institute. In 1980, Dr. Friedman began his affiliation with The Rockefeller University, where he was awarded a PhD in 1986. He was appointed Assistant Investigator with the Howard Hughes Medical Institute at Rockefeller in 1986, promoted to Associate Investigator in 1991, and promoted to Investigator in 1997. Dr. Friedman received an MD from Albany Medial College in 1977 and completed a medical residency at Albany Medical College in 1980. Dr. Friedman’s work was referred to in Time Magazine's Best of Science Section in 1995 and 1996. Among his numerous honors and awards are Popular Science's Best of Science Award (1995), the Heinrich Wieland Prize (1996), the Jacobaeus Prize (1997), the Steven C. Beering Award (1999), the Endocrinology Transatlantic Medal (2000), the Rolf Luft Award from Karolinska Hospital (2000), election to the National Academy of Science (2001), the Bristol-Myers Squibb Award for Distinguished Achievement in Metabolic Research (2001), the Passano Award (2005), election to The Royal Swedish Academy of Sciences as a foreign member (2005), the Gairdner International Award (2005), the Kovalenko Medal (2006), the Danone International Prize (2007), the Keio Medical Science Prize (2009), the Shaw Prize for Life Sciences and Medicine (2009), recognition as a Thomson Reuters Citation Laureate (2010), the Robert J. and Claire Pasarow Foundation Award (2010), the Albert Lasker Basic Medical Research Award (2010), the Foundation IPSEN Endocrine Regulation Prize (2012), the BBVA Frontier of Knowledge Award (2013), and the King Faisal International Prize in Medicine (2013).

Matthias Tschöp, MD Director, Institute of Diabetes and Obesity, Helmholtz Center, Research Center for Environmental Health

Synopsis Matthias Tschöp's work focuses on gut-brain communication as a key circuitry that regulates adiposity, food intake, glucose homeostasis, and energy metabolism. In particular, he is concentrating on the potential of afferent signaling to provide a basis for new pharmacological or device-based treatments for obesity and diabetes. Dr. Tschöp received his MD from Ludwig-Maximilians University in Munich in 1994. He then spent 4 years as a resident in internal medicine and as a research fellow in neuroendocrinology at the Munich University Hospital before accepting an invitation for a postdoctoral fellowship at the Eli Lilly Research Laboratories. During the following 3 years, he discovered the role of ghrelin in the control of food intake, metabolism, and body weight. His paper in Nature on this matter has since become one of the most cited papers in modern metabolism research. Matthias Tschöp started his own operation in 2002, first at the DIfE and then in 2003 in Cincinnati, where the College of Medicine approved his promotion to tenured full professor in January of 2009. He has published more than 140 peer-reviewed articles, including articles in Nature, Science, Nature Medicine, Nature Neuroscience, the Journal of Clinical Investigation, PNAS, Cell Metabolism, Neuron, and The Lancet. Matthias Tschöp is also the US Editor of the European Journal of Endocrinology and serves on several editorial boards, including that of the Journal of Clinical Investigation. He has received numerous awards, including the Scientific Achievement Award from the The Obesity Society (2007), the Schoeller-Junkmann Award (2001), the Lilly Research Laboratories’ President’s Award (2000), the Lilly Endocrine Research Award (2000), the European Neuroendocrine Associations Young Investigators Award (2002), and the Christina Barz Award (German Societies for Psychiatry and Neurology) (2007).

Laura Holsen, PhD Assistant Professor of Psychiatry Clinical Neuroscience Lab Brigham and Women’s Hospital Harvard Medical School

Synopsis Dr. Holsen's long-standing interests have focused on the neural circuitry of reward and emotion, especially affect-driven food motivation. Dr. Holsen’s previous experience was in studying neural mechanisms associated with phenotypic behavior in rare genetic developmental disorders, such as Prader-Willi syndrome and fragile X syndrome, and she has recently developed interests in sex differences and genetic influences in neural systems of reward and emotion. Dr. Holsen joined the team at the Connors Center in the Division of Women's Health at Brigham and Women's Hospital under Dr. Jill Goldstein to move into the arena of sexual differentiation of neural circuitry associated with affect-driven food motivation and appetite regulation and the interplay among genes, hormones, and appetite-regulatory peptides in psychiatric disorders (including depression and anorexia nervosa). Currently, Dr. Holsen is PI of an NIMH K01 award aimed at identifying the underlying neural and neuroendocrine biomarkers of disordered eating and food motivation in women with comorbid depression and obesity.

Tamas L. Horvath, DVM, PhD Chair, Section of Comparative Medicine Jean and David W. Wallace Professor of Biomedical Research Professor of Obstetrics, Gynecology, and Reproductive Sciences and Neurobiology Director, Yale Program in Integrative Cell Signaling and Neurobiology of Metabolism

DVM, University of Veterinary Sciences, Budapest, 1990 PhD, Jozsef Attila University of Sciences, 2000

Synopsis My main interest is the neuroendocrine regulation of homeostasis with particular emphasis on metabolic disorders, such as obesity and diabetes, and the effect of metabolic signals on higher brain functions and neurodegeneration. We have active research programs to pursue the role of synaptic plasticity in the mediation of peripheral hormones’ effects on the central nervous system. We also study the role of mitochondrial-membrane potential in normal and pathological brain functions with particular emphasis on the acute effect of mitochondria in neuronal transmission and neuroprotection. We combine classical neurobiological approaches, including electrophysiology and neuroanatomy, with endocrine and genetic techniques to better understand biological events at the level of the organism.

Lee M. Kaplan MD, PhD Director of the Obesity, Metabolism, and Nutrition Institute Founding Director, Weight Center at General Hospital Associate Professor, Harvard Medical School

Synopsis Dr. Kaplan is the director of the NIH-sponsored Small Animal Metabolic Surgery Core Resource, director of the subspecialty fellowship program in Obesity Medicine and Nutrition at MGH, and immediate past chair of the board of the Campaign to End Obesity. He is a member of the NIDDK Clinical Obesity Research Panel, the Scientific Advisory Board of the AGA Microbiome Center, the Executive Board of the AGA Registry, and the Certification of Obesity Medicine Physicians (COMP) Steering Committee. He currently serves as chair of the Nutrition and Obesity Section of the AGA and as chair-elect of the Bariatric Surgery Section of The Obesity Society.

Dr. Kaplan’s clinical expertise is in the areas of obesity medicine, gastroenterology, and liver disease. As the author of more than 150 medical and scientific papers, he has a special interest in the causes and complications of obesity and the development of new and more effective preventive strategies and therapies for this problem. His research is focused on the physiological and molecular mechanisms of gastrointestinal regulation of energy balance and metabolic function, and his group has pioneered the development and use of rodent models of weight-loss surgery and gastrointestinal devices to explore these mechanisms.

Dr. Kaplan graduated from and received his MD and PhD in molecular biology from the Albert Einstein College of Medicine. He completed an internship and residency in internal medicine and a fellowship in gastroenterology at the Massachusetts General Hospital and Harvard Medical School and a fellowship in genetics at Brigham and Women’s Hospital.

Jens C. Brüning, MD Director, Max Planck Institute for Neurological Research Professor of Genetics Director, Center for Endocrinology, Diabetes, and Preventive Medicine University of Cologne

Synopsis Jens Claus Brüning received his MD from the Cologne Medical School in 1993. Supported by a scholarship of the Deutsche Forschungsgemeinschaft (DFG) and a Mary K. Lacocca grant, he continued his studies as postdoctoral fellow from 1994 to 1997 in the laboratory of Professor C.R. Kahn at the Joslin Diabetes Center at Harvard Medical School in Boston. In July of 1997, he returned to Cologne and established his own research group working on transgenic mouse models of insulin resistance at the Klinik II und Poliklinik für Innere Medizin in Cologne. Jens C. Brüning has been head of the Department of Mouse Genetics and Metabolism at the Institute for Genetics at the University of Cologne since 2011 and is director of the Max Planck Institute for Neurological Research and director of the Center for Endocrinology, Diabetes, and Preventive Medicine (CEDP) at the University Hospital of Cologne. The group works on different projects aiming to characterize signalling pathways responsible for the regulation of energy and glucose homeostasis. The experimental approach focuses on the generation and characterization of transgenic and conditional knockout mouse models of insulin resistance with targeted disruption of genes in the leptin, insulin, and cytokine signalling pathways. From 2006 to 2008, he was acting director of the Institute for Genetics at the University of Cologne. In 2005, he was awarded the Ferdinand Bertram Award of the German Diabetes Society and the Science Award of the Wilhelm Vaillant Foundation in Munich, Germany. In 2006, he received the Science Award of the Lesser Loewe Foundation in Mannheim. He was awarded the Gottfried Wilhelm Leibniz Prize of the DFG in 2007, the Minkowski Award of the European Association for the Study of Diabetes (EASD) in 2008, and the Ernst Jung Award of the Ernst Jung Foundation in Hamburg, Germany, in 2009.