- 1972: B.A. New York University, New York, New York
- 1976: M.D. Mount Sinai School of Medicine, New York, New York
- 1976-1977: Intern in Medicine, George Washington University Hospital, Washington, D.C.
- 1977-1978: Resident in Medicine, George Washington University Hospital
- 1978-1979: Resident in Medicine, Beth Israel Hospital, Boston, MA
- 1978-1979: Clinical Fellow of Medicine, Harvard Medical School
- 1979-1981: Research Fellow of Toxicology Harvard School of Public Health
- 1981-1982: Research Fellow in Medicine, Harvard Medical School and Brigham and Women's Hospital
- 1981-1982: Research Fellow Section of Cellular Joslin Diabetes Center and Molecular Physiology, Research Division
Licensure and Certification
- 1979: Massachusetts License Registration
- 1979: American Board of Internal Medicine
- 1982-1987: Instructor in Medicine, Harvard Medical School
- 1987-1999: Assistant Professor of Medicine Harvard Medical School
- 1999-2010: Associate Professor of Medicine Harvard Medical School
- 2010-Present: Professor of Medicine Harvard Medical School
Hospital or Affiliated Institution Appointments
- 1982-1983: Research Associate, Joslin Diabetes Center's Section of Cellular and Molecular Physiology, Boston
- 1982-1999: Associate Physician, Brigham and Women's Hospital, Boston
- 1984-2000: Investigator, Joslin Diabetes Center's Section of Cellular and Molecular Physiology, Boston
- 1987-Present: Active Provisional Staff Beth Israel Deaconess Medical Center, Boston
- 2000-2004: Head, Section on Obesity and Senior Investigator, Joslin Diabetes Center, Boston
Other Professional Positions
- 2001-Present: Affiliate Faculty, Program in Neuroscience, Harvard Medical School
- 2002-2010: Senior Research Advisor, Peabody Society, Harvard Medical School
- 2005-Present: Associate Master, Peabody Society, Harvard Medical School
- 2006-2010: Director, Role of Discovery in Medicine, Year I course, Harvard Medical School
- 2009-Present: Director, Office for Academic Careers and Faculty Development, Beth Israel Deaconess Medical Center
- 2011-Present: Associate Member, Broad Institute
Hospital and Health Care Organization Service Responsibilities
- 1982-1990: Diabetes Attending, Joslin Diabetes Center
- 1982-1996: Diabetes Attending, Brigham and Women's Hospital
- 1982-2000: Diabetes Outpatient Clinic, Brigham and Women's Hospital
- 2000-2004: Diabetes Outpatient Clinic, Joslin Diabetes Center
- 2004-Present: Staff Physician, Beth Israel Deaconess
Major Administrative Responsibilities
- 1984-1986: Co-Organizer Longwood Medical Area Diabetes Seminar Series
- 1991-1994: Co-Organizer Longwood Medical Area Diabetes Seminar Series
- 1994-2002: Director, Molecular Core, Joslin Diabetes Center
- 1999-2002: Organizer, Longwood Medical Area Diabetes Seminar Series
- 2002-2004: Director, Animal Physiology Core, Joslin Diabetes Center
- 2004-Present: Director, Animal Physiology Core, Division of Endocrinology, Beth Israel Deaconess Medical Center
- 2006-2008: Associate Director, Endocrine Fellowship, BIDMC
Major Committee Assignments
- 1998-2004: Joslin Animal Care Committee (IACUC)
- 1999-2002: Endocrine Society, Annual Meeting Steering Committee
- 2002-Present: Ad Hoc Reviewer, Special Study Section, NPSA/NIDDK/NIH
- 2005-Present: Medical Education Reform Committee, Concentrations Subgroup
- 2006-Present: Harvard Medical School Curriculum Committee
- 2006-Present: Chair, Student Research Committee, Harvard Medical School
- 2006-Present: Ad Hoc Reviewer, NIH - IPOD (NIDDK) study section
- 2008-Present: Reviewer, Klarman Foundation Grants
- 1984-Present: American Diabetes Association, Member
- 1987-Present: The Peabody Society, Harvard Medical School, Member
- 1996-Present: The Endocrine Society, Member
- 2003-Present: Association of American Physicians (AAP), Elected
- 2003-Present: NAASO, Member
- 2005-Present: Society for Neuroscience, Member
- 2007-Present: American Physiological Society, Member
Community Service Related to Professional Work
- 1983-Present: Volunteer science teaching in elementary and high school
- 1993-2004: Co-manager of an academic internet discussion list on healthcare reform, "Healthre"
- 1999-2003 Endocrinology
- 2002-Present: Obesity Research, Associate Editor
- 2005-Present: Diabetes, Editorial Board
- 1998-Present: Ad hoc: Nature Medicine, Cell Metabolism, Proceedings of the National Academy of Science, Journal of Clinical Investigation, American Journal of Physiology
Awards and Honors
- 1972: Phi Beta Kappa
- 1980: Postdoctoral Fellowship, American Cancer Society
- 1981-1982: Mary K. Iacocca Research Fellowship, Joslin Diabetes Center
- 1998, 2002: Merck Senior Fellows Award to Maratos-Flier's Fellows
Research, Teaching and Clinical Contributions
Report of Research
Major Research Interests
- Melanin Concentrating Hormone: Physiology and Mechanism of Action
- Hypothalamic peptides and appetite regulation/Interaction of leptin with other regulators of eating behavior
- Regulation of lipid metabolism in the liver
- Narrative Report
Obesity is a significant risk factor for the development of type II diabetes. Although the prevalence of obesity is common, the causes of obesity are poorly understood. Energy balance is regulated by a complex interaction between the periphery and the central nervous system. My major interest is in the mechanisms by which melanin concentrating hormone (MCH) plays a role in energy homeostasis and in integrating signals from the environment. My laboratory initially discovered the orexigenic role of MCH using RT-PCR differential display. We found that mRNA for MCH is elevated in the hypothalamus of the leptin deficient ob/ob mouse, is regulated by fasting and that administration of MCH intracerebroventricularly into rodents led to a rapid and reproducible increase in feeding behavior.
I have subsequently followed up on this finding by generating both a line of mice lacking MCH which are lean, and a line of mice overexpressing MCH which are susceptible to diet induced obesity. Findings with the lean MCH null mice have been of significant interest; in addition to being lean these mice have significant olfactory deficits as demonstrated by behavioral deficits in mating and in tasks involving finding food. This leads me to believe that MCH is important in integrating signals from the environment, an area my laboratory is actively pursuing.
Once the MCH-receptor was identified we mapped expression in the brain of mice and found that it is heavily expressed in regions of the brain involved in olfaction including the olfactory tubercle and piriform cortex suggesting that MCH may be important in integrating olfactory information. Part of the current work in my laboratory is to develop biochemical, behavioral and anatomic correlates for MCH signaling in olfactory areas of the brain.
In addition we have used the MCH null model to further examine the role of MCH in mediating obesity in various obese models. Thus far we have found that absence of MCH attenuates obesity in ob/ob mice as well as in Ay mice which are obese due to abnormal melanocortin signaling; MCH-null mice appear to be resistant to diet induced obesity. We have also found that MCH ablation prevents diet induced obesity and has salutary effects on glucose intolerance and insulin resistance that develop with aging.
We are also exploring the relationship between MCH and motivated behavior, as MCH neurons project throughout the brain and MCH receptors are expressed in the brain. We have found that mice lacking MCH show certain altered behaviors and are also show increased susceptibility to amphetamine sensitization.
An additional area of interest is the effects of macronutrient composition of diets and their effects on metabolism and gene expressions. We have recently found that very high fat low carbohydrate diets have paradoxical effects on energy balance as the lead to weight loss coupled with increased energy expenditure as well as unique signature of gene expression in the liver. As a result of these studies my lab has found that FGF21 is a major regulator of lipid oxidation in the liver. Based on evolving results we've expanded our studies of FGF21 to include action in brown adipose tissue and pancreas as well as the role of FGF21 in the adaptation to cold. In addition we are examining the physiology of FGF21 in both obese humans and individuals with non-alcoholic fatty liver disease.
Finally I've expanded my efforts in the area of translational research and have been studying the effects of the anti-diabetic agent exenatide on weight loss in non-diabetic obese humans.
Between 2007 and 2010, I was involved in developing and co-directing a new, one month, required course for first year HMS students, the Role of Discovery in Medicine. The goal of this course is to highlight the critical importance of research in changing medical paradigms and medical practice and to examine methodology essential to the process of discovery. This course has evolved and is now an elective for students planning to submit proposals for funding from HMS for either bench or clinical/translational research. Two diseases, Obesity/Type II diabetes and Breast Cancer were used as disease paradigms in seminars aimed at assisting students in assembling high quality research proposals. A series of lectures in the fall cover such topics such as approaches to clinical versus bench research, finding a lab and writing a research proposal.
My current teaching responsibilities also involve the ongoing supervision of four post-doctoral research fellows in my laboratory. I have supervised senior thesis of three seniors at Harvard college. I mentor and act as a senior advisor to two junior level investigators. I also participate as an invited speaker in the CBC course and in the IHP course at Harvard Medical School. I teach in the Endocrinology course organized by Dr. Monty Krieger at MIT.
I also served as a tutor in the second year HMS course "Nutrition and Preventative Medicine."
I see outpatients with diabetes one morning every other week as a consultant. This clinical activity takes place at Beth Israel Deaconess Medical Center. Approximately 90% of my patients involve long term follow up. The one morning clinic generates an addition two to four hours of follow up time in the form of patient phone calls and communication with referring physicians. Diabetes particularly requires particularly intensive phone follow up for the purpose of blood sugar monitoring.
Research Funding Information (entirely for bench research)
- 1983-1984: Juvenile Diabetes, PI, "Viral Interactions with Foundation 82R609 Beta Cells"
- 1984-1989: NIH Award 5K08AM1252, Clinical Investigator PI, "Viral Pathogenesis in Endocrine Cells"
- 1984-1986: American Diabetes Association, "Cellular Processing of Reovirus and Infection of Islet Cells"
- 1989-1992: American Heart Association, PI, "Viral Receptors on Endocrine Cells"
- 1990-1995: NIH R01 A128971-05, PI, "Molecular Characterization of the Reovirus Receptor"
- 1994-1999: Markey Charitable Trust, PI, "DNA Sequencing & Oligonucleotide Synthesis Core"
- 1995-1996: Boston Obesity Research Center NIH 5P30DK46200-04, PI, "Identification of Novel Hypothalamic Genes that are Differentially Regulated"
- 1996-1997: American Diabetes Association, PI, "Melanin Concentrating Hormone:A Novel Orexigenic Neuropeptide"
- 1996-1997: NIH 5P30DK36836-11, PI, "MCH: A Novel Regulator of Feeding Behavior"
- 1996-1998: Eli Lilly and Company, PI, Study directed to Obesity, Energy Homeostasis and Metabolic Control
- 1998-2003: NIH 1R01DK53978, PI, "Anatomic and Physiologic Characterization of MCH Action"
- 1999-2004: NIH 1R01DK56113, PI, "Gene Targeting Approaches to MCH and Energy Balance"
- 2000-2010: NIH 1P01DK56116-06, PI, J.S. Flier PI on Program Project, Program Project Grant with BIDMC
2007-2010: Amylin Pharmaceuticals, PI, "The Effect of Exenatide on Weight Loss, Energy Expenditure and Hunger in Obese Women Without Diabetes"
- 2005-2011: NIH R01DK069983-05, PI, "Actions of MCH in the Brain" (no cost extension)
- 2011-2015: NIH R01DK028082-29, PI "Metabolic Actions of FGF1"
- 2012-2014: Amylin Pharmaceuticals, PI, "Patterns, predictors and mechanisms of weight loss with exenatide treatment in overweight and obese women without diabetes"
- 2011-2012: Jeffrey B Picower Foundation, PI, "Molecular mediators of FGF21 action"
Report on Current Research Activities:
Report on Teaching
- Medical School Courses
- 1982-1996: Teaching of residents and fellows while Attending Physician at Brigham and Women's Hospital, Boston, Massachusetts
- 1982-2004: Supervised research training of 1-2 M.D. Postdoctoral Fellows, medical and college students and Research Assistants at the Joslin Diabetes Center, Boston, Massachusetts
- 2004-Present: Supervised research training of 3-4 MD or PhD postdoctoral fellows, medical students and undergraduates in the Endocrine Division of Beth Israel Deaconess Medical Center
- 1984-1988: First year medical tutor at Harvard Medical School, Boston, Massachusetts.
- 1988-1992: Tutor in Patient/Doctor I, Harvard Medical School - This course meets weekly throughout the academic year. In addition to a two hour tutorial approximately two additional weeks of time outside the classroom for observation of students, with patients, discussions and feedback were required
- 1991-1994: Advisor, Peabody Society in Pilot Advisory Program, Harvard Medical School
- 1995-2005: Participated as lecturer and tutor in CBC, 5 hours each time
- 2005-2006: Tutor, Prevention and Nutrition
- 2006-Present: Co-director, Role of Discovery in Medicine, required course for first-year Harvard Medical Students
- April 2007: Thesis Committee, Jacob Newman Marcus, Orexin Receptors and the Central Autonomic System, Harvard Medical School
- December 2007: Thesis Committee, Thaddeus John Unger, Examination of Deficits in Energy Balance and Affective Behavior Following Central or Hypothalamic Depletion of Brain-Derived Neurotrophic Factor, Tufts University
- Advisory and Supervisory Responsibilities
- 1982-1996: While an attending physician at the Brigham, I met with fellows and residents three times per week while on service (two months of the year.) The sessions were devoted to presentation of patients and discussion and teaching. (They were not used for provision of clinical services.)
- 1994-Present: Supervise research for two-five research fellow (approximately 350 hrs/yr)
- 2005-2008: Co-direct, Endocrine Fellowship Program with Dr. Evan Rosen
- Advisees and Trainees:
- 1986-1989: Eric Verdin (postdoctoral fellow), Professor of Medicine, UCSF
- 1989-1991: Louise Montgomery (postdoctoral fellow), Associate Professor of Biology, Chairman Department of Biology, Marymount University, Arlington, VA
- 1991-1993: Ali El-Ghorr (postdoctoral fellow), Faculty Division of Biomedicine and Clinical Laboratory Sciences, University of Edinburgh
- 1994-1997: Daqing Qu, (postdoctoral fellow), Research Scientist, Millipore Corporation
- 1997-1999: David Ludwig (postdoctoral fellow), Associate Professor, Harvard Medical School, Children's Hospital, Boston
- 1997-2001: Nicholas Tritos, (postdoctoral fellow), Instructor in Medicine, Massachusetts General Hospital, Boston, MA
- 2002-2005: Richard Bradley (postdoctoral fellow), Private sector, business development
- 1997-2000: Jason Mastaitis (pre-doc), Ph.D., Department of Neurobiology, Mount Sinai School of Medicine, New York, New York
- 2000-2003: Daniel Trombly (pre-doc), Graduate student, Department of Neuroscience, Northwestern University, Chicago, Illinois
- 2001-2002: Jason Karamachandran (senior thesis) Pathology Resident, Stanford University, San Francisco, California
- 2002-2003: Neha Jadeja, (senior thesis), Medical Student, Harvard Medical School, Boston
- 2001-2003: Gabriella Segal-Lieberman (postdoctoral fellow) Assistant Professor of Medicine, Sheba Medical Center Institute of Endocrinology, Ramat-Gan, Israel
- 2001-2004: Efi Kokkotou, (postdoctoral fellow), Assistant Professor of Medicine, Harvard Medical School, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston
- 2002-2006: Pavlos Pissios, (postdoctoral fellow), Instructor in Medicine, Harvard Medical School, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston
- 2003-2007: Justin Y. Jeon, (postdoctoral fellow), Assistant Professor, Exercise Physiology, Korea
- 2003-2007: Adam R. Kennedy, (postdoctoral fellow), Staff Scientist, Jackson Laboratories, Sacramento, California
- 2005-2011: F. Martin Fisher, (postdoctoral fellow), Instructor, Beth Israel Deaconess Medical Center
- 2007-2011: Andrew C. Adams, (postdoctoral fellow), Staff Scientist, Lilly Pharmaceuticals
- 2009-2011: Patricia Chui, (postdoctoral fellow), Surgical Resident, Brigham and Women's Hospital
Regional, National or International Contributions
- May 2000: Department of Physiology Seminar, University of Massachusetts Medical School, Worcester, MA
- October 2000: Inaugural Obesity Research Center Symposium, Boston University, Invited Speaker
- May 2003: Pat Usher Memorial Lecture, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston
- October 2006: Beth Israel Deaconess Research Day, Invited Speaker
- October 2008: Brigham and Women's/Children's Hospital, Endocrine Grand Rounds
- December 2008: Longwood Medical Area Diabetes Seminar, Joslin Diabetes Center
- July 2009: Boston Obesity and Nutrition Research Center Annual Symposium
- August 1996: Aspen Lipid Conference
- February 1997: Maui Meeting on Diabetes and Obesity
- June 1997: Endocrine Society, 79th Annual Meeting, Symposium Speaker
- September 1997: National Institute of Health, NIDDK, "The Brain and the Adipocyte"
- March 1998: Pennington Biomedical Research Center, "Nutrition, Genetics and Obesity"
- June 1998: American Diabetes Association, 58th Annual Meeting, Symposium Speaker "Neuroendocrine Regulation of Energy Balance and Satiety"
- October 1998: Banbury Conference/Cold Spring Harbor, "The Molecular Physiology of Weight Regulation and Obesity"
- June 1999: Endocrine Society, 81st Meeting, Symposium Speaker
- February 2000: Keystone Symposium, Invited Speaker
- February 2001: Keystone Symposium, Invited Speaker
- January 2002: Keystone Symposium, Molecular Control of Adipogenesis and Obesity, Invited Speaker
- July 2002: Gordon Research Conference, Mechanism of Hormone Action, Invited Speaker
- February 2003: AAAS Symposium Speaker
- June 2004: 8th Neuroendocrine Workshop, Invited Speaker
- June 2004: Endocrine Society's 86th Annual Meeting, Symposium Speaker
- January 2005: Keystone Symposium, Invited Speaker
- May 2006: Appetite and Obesity, Cold Spring Harbor Symposium, Invited Speaker
- May 2008: New York Academy of Sciences, Invited Speaker
- June 2008: Endocrine Society, Annual Meeting, Symposium Speaker
- January 2009: Keystone Symposium, Invited Speaker
- August 2009: Kern Aspen Lipid Conference, Invited Speaker
- April 2010: Presidential Symposium, American Society for Nutrition, Invited Speaker
- June 2010: American Diabetes Association, Annual Meeting, Invited Speaker
- March 2011: Endocrine Grand Rounds, University of Pennsylvania
- November 2011: Endocrine Grand Rounds, Brown University
- December 2011: Endocrine Grand Rounds, Columbia University
- January 2012: Keystone Symposium, Invited Speaker, Plenary Session
- June 2012: Endocrine Society, Annual Meeting, Invited Speaker
- July 1997: International Diabetes Foundation, Helsinki Meeting
- August 1998: Adipo- Science Meeting, Osaka, Japan
- November 1999: Institut Pasteur, Euroconference "Obesity: Genetics, Pathophysiology and Therapeutics," Invited Speaker
- March 2004: Days of Molecular Medicine, Cambridge, England, Invited Symposium Speaker
- August 2012: Australian Diabetes Association, Brisbane Australia, Annual Meeting
- 2000-2003: Endocrine Society, Meeting Organizing Committee
- 2007: Keystone Symposium, Organizer: Obesity, Peripheral and Central Pathways Regulating Energy Homeostasis
For a complete listing of Dr. Maratos-Flier's publications,