Scientific Advisory Board
Dr. Schwartz is Robert H. Williams Endowed Chair, Professor of Medicine in the Division of Metabolism, Endocrinology and Nutrition at the University of Washington and Director of the UW Medicine Diabetes & Obesity Center of Excellence. His research investigates brain mechanisms governing energy balance and glucose metabolism and how obesity and diabetes result from impairment of these brain systems. He has published more than 200 articles related to these topics and his research has been continuously funded by the NIH since joining the faculty of UW 20 years ago. Dr. Schwartz is a member of the Association of American Physicians, the Western Association of Physicians and the American Society for Clinical Investigation, is the recipient of the 2007 Williams-Rachmiel Levine Award for Outstanding Mentorship from the Western Society for Clinical Investigation, the 2006 Naomi Berrie Award for Outstanding Achievement in Diabetes Research from Columbia University, and was the 2011 Solomon A. Berson Lecturer for the American Physiological Society, among other awards. He is a member of the editorial boards of the Journal of Clinical Investigation, American Journal of Physiology, Endocrine Reviews, Molecular Metabolism and Frontiers in Neuroendocrinology.
Michael Cowley is the founding director of the Monash Obesity & Diabetes Institute and a physiologist with a focus on obesity, diabetes, and metabolic disorders. He has published more than 70 papers and chapters, is the inventor of 85 patents, and the founder of Orexigen Therapeutics, a publically listed (NASDAQ: OREX) San Diego biotech company where he served as the Chief Scientific Officer till December 2008. Michael is a Professor of Physiology at Monash University, and a director of an Australian diabetes drug development company, Verva Inc, and a primate contract research company, PDS. His work has mapped the neural circuits in the brain that sense nutrients and fat, to control appetite and body weight.
My group develops novel physiological MRI methods for the study of healthy and diseasedbrain. I am particularly interested in techniques for mapping the macroscopic and microscopic neurovasculature. I collaborate closely with various clinical groups, in particular through the Oxford Acute Vascular Imaging Centre, on the development of rapid imaging approaches to aid in the diagnosis and treatment of acute stroke. A second thread of research aims to advance ultra-high field imaging, utilizing our 7-tesla scanner. This research combines novel imaging hardware, including parallel RF transmission, with state-of-the-art acquisition techniques. Finally, I also work with the Dept of Psychiatry on the development of spectroscopic measurement of neurotransmitters. I am an active member of University College and hold leadership roles in several imaging centres within Oxford (including OCMR and AVIC). In the broader scientific community, I serve the International Society for Magnetic Resonance in Medicine in several capacities.
Neurophysiology of feeding; Chemical senses; Neuroimaging; Dopamine; Addiction; Motivation; Psychophysics; Stress; Obesity
The role of the amygdala in weight-gain susceptibility
Cognitive and affective influences on gustatory processing
Neural correlates of flavor processing
The influence of smoking on brain encoding of food
Neural correlates of flavor nutrient conditioning
Top-down influences on brain encoding of flavors and foods
Neuroimaging techniques such as functional magnetic resonance imaging (fMRI) and positron emission tomography have made it possible to study brain representation of sensation, motivation and cognition in humans. The primary interest of my lab is to use these techniques in conjunction with psychophysics and behavioral testing to uncover brain substrates of taste, smell, flavor, and food reward. We are particularly interested in multisensory integration of taste and smell as well as in understanding how sensory processing interacts with behavioral choices such as decisions to eat or stop eating in healthy individuals and in people with eating disorders. A new research aim is to examine similarities and differences in the neural representation of food and drug reward to answer questions such as how nicotine addiction may influence the ability of food odors to induce eating. We currently have a fully automated and fMRI compatible olfactometer and gustometer and are using these devices to study taste, smell and food reward in the 3 Tesla Magnet at the Yale MR Imaging Research Center.
Current Journal Service: Reviewing Editor, Biological Psychiatry, Topic Editor, Molecular Metabolism, Editorial Board Member, Neuroimage: Clinical; Guest Editor 2013, Special Issue “Food Addiction”, Biological Psychiatry;
Current Advisory Boards: Helmholtz Alliance Imaging and Curing Environmental Metabolic Diseases; European Associations for the Association for the Study of Diabetes Treatment Strategies
Current Grant Review Panels: NIH NIDCD CDRC; NIH NIDDK DDK-C; DFG Planned Transregional Collaborative Research Center
Current Funding: NIH NIDCD R016706; NIH NIDDK R01DK085579; NIH NIAAA P50 AA012870
Dr. Elmquist’s research focuses on identifying the pathways in the brain regulating food intake, 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. This will hopefully aid the understanding of how the nervous system regulates feeding, body weight, insulin secretion by the pancreas, and glucose homeostasis.
Stephanie Fulton received her graduate training in Behavioural Neurobiology at Concordia University in Montreal under the mentorship of Drs Peter Shizgal and Barbara Woodside. Her PhD thesis investigated the impact neuropeptides and hormones involved in energy homeostasis, such as the adipose-derived hormone leptin, on brain reward circuitry. As a CIHR-funded postdoctoral fellow, she joined the laboratory of Dr Jeffrey Flier at Harvard Medical School and Beth Israel Deaconess Medical Center in Boston to pursue training in energy metabolism and neuroendocrinology. There her work identified the influence of leptin on dopamine tone and function in the mesoaccumbens pathway. Dr Fulton then returned to Montreal as an NSERC postdoctoral fellow to study dopamine neurophysiology in the laboratory of Dr Louis-Eric Trudeau where she explored the regulation of striatal dopamine release by the D2 dopamine autoreceptor. In 2008, Dr Fulton became a member of the Montreal Diabetes Research Center and was appointed Assistant Professor of the Department of Nutrition and Adjunct Assistant Professor of the Department of Physiology in the Faculty of Medicine at Université de Montréal. Dr Fulton’s laboratory is situated at the Technopôle Angus research site of the Centre de Recherche du CHUM.
Our laboratory studies the neural mechanisms of food-motivated behavior. Peripherally-derived metabolic signals can directly modulate mesolimbic dopamine neurons, an important component of the neural circuitry controlling motivation and reward-relevant learning. We are investigating how peripherally-derived hormones and nutrients alter dopamine and other reward-related pathways to affect food-motivated behavior and preference for foods high in fat and sugar. We are also interested in the neural adaptations that may occur in response to consumption of palatable high-energy foods and how they may contribute to over-eating and the development of obesity.
Sabrina Diano, PhD
Associate Chair for Faculty Development
Dept. Ob/Gyn and Reproductive Sciences
Program in Cell Signaling and
Neurobiology of Metabolism
Depts. Ob/Gyn, Neurobiology and Comparative Medicine
Yale University School of Medicine and Graduate School
Dr. Sabrina Diano is a Tenure Professor in Departments of OB/GYN & Reproductive Sciences, Neurobiology and Comparative Medicine at the Yale University School of Medicine. She is also part of the Integrative Cell Signaling and Neurobiology of Metabolism (ICSNM), and Interdepartmental Neuroscience Program here at Yale. She graduated with honors from the University of Naples “Federico II”, Naples, Italy. She conducted her post doctoral studies here at Yale where she became faculty in 2000.
Her research focuses on CNS (hypothalamic) mechanisms relating to the regulation of energy homeostasis, with emphasis on hormone action in the hypothalamus. Her studies on hypothalamic inter- and intra-cellular mechanisms that regulates energy metabolism add critical information to the current understanding of the central regulation of energy balance and how alterations in stored energy are sensed in the hypothalamus. The results of her research have important implications for understanding the pathogenesis of metabolic syndrome, obesity and type 2 diabetes, disorders that are the leading cause of morbidity and mortality in the U.S., and the developed world in general, with the highest financial burden on the National economy.
MAJOR RESEARCH CONTRIBUTIONS
1987 Co-Inventor of Lanreotide (Somatuline) (Neuroendocrinology 45: 429)
1995 1st to discover that leptin inhibits NPY expression and secretion (Nature 377:530)
1996 Developed 1st leptin RIA and demonstrated elevated levels in obesity (NEJM 334:292)
2000 1st to demonstrate that ghrelin induces a positive energy balance (Nature 407: 908)
2003 Initiated qNMR development to measure body composition (Anal Bioanal Chem 377: 990)
FACULTY POSITIONS HELD
1982 – 1984 Research Instructor, Department of Medicine, Tulane University
1984 – 1986 Research Assistant Professor, Department of Medicine, Tulane University
1994 – 2009 Adjunct Professor of Biology, IUPUI, Indianapolis, IN
2010-Today Adjunct Associate Professor of Medicine, Tulane University
Visiting Scientist, Agricultural Research Station of USDA, New Orleans
Adjunct Associate Professor, Pennington Biomedical Research Center
INDUSTRY POSITIONS HELD
1987-1989 Senior Scientist, Lilly Research Laboratories.
1989-1995 Research Scientist, Lilly Research Laboratories.
1996- 2001 Senior Research Scientist, Lilly Research Laboratories.
2001-2004 Research Advisor, Lilly Research Laboratories.
2004- 2009 Chief Scientific Officer, Obesity, Lilly Research Laboratories.
2009-2010 Research Fellow, Lilly Research Laboratories.
2010-Today VP Research and CSO, MicroBiome Therapeutics (formerly NuMe Health)
Wolfgang Langhans (WL) received a DVM (Summa cum Laude) from the University of Munich 1981, was awarded the Hans Adolf Krebs Prize by the German Nutrition Society in 1982, and spent two months in 1983 at the New York Hospital-Cornell Medical Center in White Plains, NY, learning neurosurgical techniques. WL joined the Institute of Veterinary Physiology at the University of Zurich in 1983, where he completed habilitation in 1987. He became a full Professor at ETH Zurich in 1988, where he still remains, despite attractive offers from other institutions. In 1996 WL spent a six-month sabbatical at Johns Hopkins University School of Medicine in Baltimore, MD, where he developed expertise in single unit electrophysiological recording.
WL was Head of the Institute of Animal Sciences from 1992 to 1993 and from 2006 to 2009, and Chair of the Department of Agricultural and Food Sciences (D-AGRL) from 1997 to 1999. From 2003-2006, as Dean of VETSUISSE, WL was charged with the task of merging the Faculties of Veterinary Medicine in Zurich and in Bern into a unified VETSUISSE Faculty. During this time, he continued to run his laboratory, but was relieved from teaching and administrative duties. In 2010 WL became Chair of a strategic planning committee for the establishment of the new Department of Health Sciences and Technology (D-HEST) at ETH Zurich. He is currently (since January 2012) the Chair of this department. Also, WL has served in various functions (President, Program Committee Chair, Long-Range Planning Committee Chair) for the Society for the Study of Ingestive Behavior (SSIB) and was President of the Swiss Nutrition Society (2007-2011).
WL’s research aims at characterizing physiological mechanisms that control eating and energy balance and their disturbances. After working many years on the anorexia during infection and on the role of peripheral metabolism in the control of eating, his current research focuses on gut peptides and fatty acid oxidation in this context. He uses rats and mice in a translational, integrative and systemic approach comprising all levels of scientific analysis, from the molecular through the cellular level to the behavior in an intact organism. A unique strength of his group is the use of sophisticated methods to isolate and manipulate specific critical components of the gut-brain axis. These include experimental surgical procedures allowing for the routine use of in vivo techniques that are rarely found elsewhere. Recent discoveries of WL’s group include the findings that ghrelin does not require abdominal vagal afferents to inhibit eating and that peripheral glucagon-like peptide-1 (GLP-1) can inhibit eating by acting on GLP-1 receptors at two different sites, i.e., on intestinal vagal afferents and in the hindbrain. Also, based on a series of recent studies WL proposed the novel hypothesis that the intestine, rather than the liver, meters the energy content of dietary fat by fatty acid oxidation sensing and generates a vagal afferent signal that influences eating. WL has had continuous extramural funding for his research for almost 30 years, he has mentored > 70 doctoral theses (PhD and DVM), published > 170 peer-reviewed research papers, and > 75 invited review articles and book chapters. In addition, he has given > 170 invited talks at international meetings and guest lectures. Together with Nori Geary he edited the book “Frontiers in Eating and Weight Regulation” (2010) that features a collection of 15 expert descriptions of the important research frontiers in the physiology of eating. Currently (since July 2013) WL serves as an Associate Editor for the American Journal of Physiology (Regulatory, Comparative and Integrative Physiology).
The overall goal of the Experimental Neuroimaging Group is to develop and apply imaging methods to improve our understanding of the biology of secondary cancer to the brain, or brain metastasis. The emphasis of our research programme is on whole system, in vivo, studies, with particular interest in magnetic resonance (MR) based methods. Our specific aims are (1) to develop imaging methods for early detection and monitoring of brain metastases, (2) to identify the role of inflammatory processes in the development of brain metastases, and (3) to determine the consequences of brain metastases on brain metabolism and function.
Over the last 20 years, we have studied a number of models of human disease, including stroke, multiple sclerosis (MS), cerebral malaria and prion disease. We have a particular interest in the contribution of inflammatory processes to the development and progression of neurological disease. In 2007 the Group relocated to the Gray Institute, and we are now taking what we know from our previous work into the field of cancer and, in particular, brain metastasis.
We use a broad range of MRI techniques, including fMRI, together with magnetic resonance spectroscopy (MRS) approaches for measuring aspects of cerebral metabolism. In addition, we have worked extensively in the area of molecular MRI, with the aim of finding new methods of detecting neurological disease early, thus improving diagnosis and enabling targeted therapy. Recently we have demonstrated that one of these approaches enables very early detection of brain metastases, and we are now taking this method through the translational pipeline to clinical trial (funding MRC DPFS grant 0902181):
We anticipate that meeting our objectives will open new avenues for clinical interrogation of brain metastases, enabling improved and earlier detection of this devastating disease, and will identify new routes of therapeutic intervention.
Specific areas currently being studied include:
Role of endothelium, astrocytes and microglia in brain metastasis.
Contribution of systemic inflammation to the progression of brain metastasis
Functional and metabolic response of the brain to metastases.
New molecular imaging approaches for detection and monitoring of tumours.
Selective permeabilisation of the blood-brain barrier at sites of brain metastases for targeted therapy and detection.
Biofluid metabolomics detection of neurological disease, including brain metastasis.
New MRI methods for assessment of the tumour microenvironment.
In addition to our primary interest in brain metastasis, we also have collaborative projects in the areas of medulloblastoma, glioblastoma and lung metastasis. At the same time our previous research programmes in neurovascular and neurometabolic coupling, pharmacological MRI, CNS inflammation (MS and ALS in particular) and the development of new MRI techniques for neuroimaging are on-going.
Dr. Zeltser is an assistant professor in the Naomi Berrie Diabetes Center and the Department of Pathology and Cell Biology. Dr. Zeltser graduated from Princeton University and received her Ph.D. from The Rockefeller University. She continued her research training in development neurobiology as a postdoctoral fellow in the laboratories of Andrew Lumsden at Kings College London and Claudio Stern and Thomas Jessell at Columbia University. Her laboratory studies the development of hypothalamic circuits regulating food intake and body composition.
Dissection of neuronal circuits that are involved in thermoregulatory leptin action to regulate energy expenditure and obesity.
Integration of diverse sensory inputs (e.g. cold, diet, reproductive hormones) to appropriate thermoregulatory output (energy expenditure).
Dissection of neuronal circuits that control nutrient reward and preference.
Role of galanin and leptin in nutrient reward and preference.
Pharmacogenetic and Optogenetic dissection of neuronal circuits for complex behavior (energy expenditure, nutrient reward/preference).
Optogenetic circuit mapping.
Dr. D’Alessio is an Associate Professor of Medicine, in the Division of Endocrinology, and holds the Albert Vontz chair in Diabetes Research. He joined the faculty at University of Cincinnati in 1999. Dr. D’Alessio has received national recognition for research on gastrointestinal hormones and the regulation of insulin secretion. He has published widely in this area, as well as in related aspects of energy metabolism and nutrition. Dr. D’Alessio is ABIM certified in Internal Medicine and Endocrinology and attends the Diabetes and Endocrine clinics at University Hospital and the Cincinnati VA hospital. He is a member of the Endocrine Society, American Diabetes Association, American Heart Association, and serves on the national council for the American Federation for Medical Research.
The primary focus of Dr. D’Alessio’s research is the regulation of insulin secretion and glucose tolerance in type 2 diabetes, and specifically the influence of intestinal hormones on these processes. In addition, he has additional projects to investigate the actions of GI peptides to control food intake and body weight. Central themes that are common to all of this research is the interaction of ingested nutrients with endocrine signaling systems, and the interface between hormones and the nervous system. The overall goal of this work is to better understand the physiologic mechanisms underlying nutrient metabolism and apply this knowledge to the treatment of diabetes and obesity. Specific projects underway in Dr. D’Alessio’s lab include:
Regulation of insulin secretion by the gut-brain peptide glucagon-like peptide 1 (GLP-1) in healthy and diabetic humans. This project focuses on the role of GI hormones in mediating the insulin response after meals and how this response is impaired in diabetes. These studies are designed to compare rates of GLP-1 secretion in response to nutrients, the sensitivity to GLP-1 action , and insulin-independent effects of GLP-1 in diabetic and control subjects.
Regulation of food intake by GI hormones. This project is tied to a larger study of the mechanisms by which high-fat diets induce obesity. Experiments have been designed to elucidate how chronic changes in the lipid content of the diet affect the secretion of, and responsiveness to gut peptides that regulate satiety.
The mechanisms by which the GLP-1 suppresses food intake. This project evaluates the hypothesis that GLP-1 inhibits food intake as part of a broader spectrum of nausea and illness actions. Studies are designed to test the hypothesis that GLP-1 is a central mediator of many of the symptoms of general illness and thus may have a role in the response to many chronic diseases.
The synthesis, secretion and action of a novel peptide produced in the intestinal tract. This peptide was recently identified and isolated from the intestinal tract of mammals and has considerable homology to somatostatin, but appears to be the product of another gene. Studies in animals and humans have shown that this peptide is secreted in response to ingested nutrients, especially dietary fat, and that it appears to inhibit food intake. Studies are currently in progress to identify the gene producing this peptide, delineate the cells that produce it and determine its role in normal physiology.
Dr. D’Alessio joined the faculty at the University of Cincinnati in 1999. He has published widely in gastrointestinal hormones and the regulation of insulin secretion as well as in related aspects of energy metabolism and nutrition. He is ABIM certified in Internal Medicine and Endocrinology and serves as an attending in the Diabetes and Endocrine subspecialty clinics at the Cincinnati VA Hospital. He is a member of the Endocrine Society, the American Diabetes Association, and the American Federation for Medical Research. Dr. D’Alessio is also a faculty member in the Pathobiology and Neuroscience programs at the University of Cincinnati.