BIOGRAPHICAL SKETCH Provide the following information for the Senior/key personnel and other significant contributors. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE Rexford S. Ahima Professor of Medicine, University of Pennsylvania eRA COMMONS USER NAME (credential, e.g., agency login) AHIMAR EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) DEGREE INSTITUTION AND LOCATION MM/YY FIELD OF STUDY (if applicable) Univ. of London, The Middlesex Hosp Med Sch B.Sc. 1981 Endocrinology Univ. of Ghana Medical School, Accra, Ghana M.D. 1986 Medicine Tulane University, New Orleans, Louisiana Ph.D. 1992 Neuroscience Albert Einstein College of Medicine, New York Specialty 1995 Internal Medicine Research and Endocrinology, Beth Israel Deaconess Medical Center; Harvard Clinical 1998 Diabetes and Medical School, Boston, MA Fellowship Metabolism
A. Personal Statement My research focuses on the central and peripheral actions of hormones secreted by adipose and skeletal muscle. Leptin and adiponectin stimulate fat oxidation, decrease steatosis, and enhance insulin sensitivity, partly by acting on MC4R neurons in the hypothalamus. In contrast, resistin induces hepatic inflammation, insulin resistance and steatosis by targeting neuropeptide Y neurons in the arcuate nucleus. Recently, we have characterized the metabolic actions myokines, particularly myostatin and IL 15. Deletion of mstn increases muscle mass, decreases body fat, and improves insulin sensitivity. Interestingly, inhibition of myostatin promotes the browning of white adipose, leading to increased thermogenesis. Deletion of Il15R α promotes oxidative muscle reprogramming, increases exercise endurance and energy expenditure, and decreases obesity. A better understanding of the metabolic effects of myokines could provide novel insights into the pathogenesis and treatment of sarcopenia associated with aging and obesity. I am the Director of the Penn Diabetes Research Center Mouse Metabolic Phenotyping Core, which performs state of the art metabolic studies, including body composition measurement using nuclear magnetic resonance (NMR) and DEXA, CLAMS monitoring of feeding, locomotor activity, sleep epochs and energy expenditure, and clamp and radioisotopic tracer kinetic studies in mouse models. I have served on grant review committees of the National Institutes of Health, Howard Hughes Medical Institute, and Wellcome Trust Research, and previously as an associate editor of Gastroenterology , and the Journal of Clinical Investigation . I am currently a member of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Board of Scientific Counselors, associate director of the University of Pennsylvania Institute for Diabetes, Obesity and Metabolism, editor of the Annals of the New York Academy of Sciences Year in Diabetes and Obesity , and consulting editor of the Journal of Clinical Investigation , and Molecular Metabolism . I addition to my basic science research, I serve as an attending endocrinologist at the Hospital of the University of Pennsylvania, and also collaborate on clinical research focusing on obesity and metabolic syndrome.
B. Positions and Honors
Positions and Employment 1986 1988 Houseofficer in Medicine and Surgery Korle Bu Teaching Hospital, Accra, Ghana 1988 1992 Graduate fellowship, Tulane University School of Medicine (mentor: Richard Harlan) 1992 1995 Intern and Resident Department of Medicine, Albert Einstein College of Medicine, NY 1995 1998 Research fellowship (mentor: Jeffrey Flier), and Clinical fellowship in Endocrinology, Diabetes & Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 1998 1999 Instructor of Medicine, Harvard Medical School; Attending Physician; Department of Medicine, Division of Endocrinology, Beth Israel Deaconess Medical Center, Boston, MA 1999 present Attending Endocrinologist, University of Pennsylvania Health System 1999 2005 Assistant Professor of Medicine, Division of Endocrinology, Diabetes & Metabolism, University of Pennsylvania 2005 2008 Associate Professor of Medicine, University of Pennsylvania 2008 present Associate Professor of Medicine (with tenure), University of Pennsylvania 1999 present Director, Mouse Metabolic Phenotyping Core, Diabetes Endocrinology Research Center 2001 present Director, Weight Management & Metabolism Program 2005 present Associate Director, University of Pennsylvania Institute for Diabetes, Obesity & Metabolism 2005 present Director of Obesity Unit, University of Pennsylvania Institute for Diabetes, Obesity & Metabolism 2012 present Professor of Medicine (with tenure), University of Pennsylvania
Other Experience and Professional Memberships 1997 present Member of The Endocrine Society, American Diabetes Assoc; American Association for the Advancement of Science; Society for Neuroscience; The Obesity Society (NAASO); American Physiological Society; American Society for Clinical Investigation 1997 present Reviewer for Nature; Cell; Molecular Cell; Cell Metabolism; Nature Medicine; Science; Proc. Natl. Acad. Sci.; Endocrinology; Journal of Clinical Endocrinology & Metabolism; Diabetes; J. Clinical Investigation; Journal of Biological Chemistry; Molecular and Cellular Biology; American J. Physiology; New Engl. J. Med.; Gastroenterology 2003 present Editorial Board, Diabetes (2003 2006); Associate Editor, Gastroenterology (2007 2011), Editorial Board, Journal of Clinical Investigation (2007 2010); Endocrinology (2008 2012); Obesity Online (2008 2009) 2000 present Faculty Cell and Molecular Biology, Neuroscience and Pharmacology Graduate Groups, 2001 present Ad hoc reviewer: National Institutes of Health Endocrinology Study Section; Special Emphasis Panels (NIDDK, NIMH, Shared Instrumentation), NCRR COBRE; Member of IPOD Study Section (2006 2010) 2001 present Reviewer for the Wellcome Trust Research, UK; Scottish Medical Research; DERC Pilot Awards Univ. of Pennsylvania, Harvard/MGH, Yale Medical School; DTRC Pilot Awards University of Michigan and Albert Einstein College of Medicine; Boston Obesity Research Center 2005 2007 Howard Hughes Medical Institute, Medical Research Fellowship Review Board 2007 2012 Member of the Board of Scientific Counselors, National Institute on Alcohol Abuse and Alcoholism (NIAAA) 2008 2009 Member of NIH Diabetes Strategic Planning Committee (Obesity Sub group)
Honors 1986 Best Final MB Student Prize, University of Ghana Medical School 1989 Owl Club Award, Tulane University, New Orleans, LA 1991 Gold Medal, Anatomical Society of West Africa 1993 Leo Davidoff Award, Albert Einstein College of Medicine, New York 1997 1999 Pfizer Postdoctoral Fellowship Award, Harvard Medical School, Boston, MA 2005 Elected member of the American Society for Clinical Investigation (ASCI) 2008 Fellow of The Obesity Society 2009 The Albert Stunkard Founder’s Award, Center for Weight and Eating Disorders, University of Pennsylvania 2010 Elected member of the Association of American Physicians (AAP) 2010 Pat Usher Memorial Lecturer, Beth Israel Deaconess Medical Center, Boston 2012 Harvard Medical School Diversity and Community Partnership Lecturer
C. Selected Peer-reviewed Publications (15 out of 125) 1. Ahima, R.S. , Prabakaran, D., Mantzoros, C., Qu, D., Lowell, B., Maratos Flier, E., Flier, J.S.: Role of leptin in the neuroendocrine response to fasting. Nature 382: 250 252, 1996. PMID8717038 2. Steppan, C.M., Bailey, S.T., Bhat, S., Brown, E.J., Banerjee, R.R., Wright, C.M., Patel, H.R., Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 409:307 312, 2001. PMID11201732 3. Qi, Y., Takahashi, N., Hileman, S.M., Patel, H.R., Berg, A.H., Pajvani, U.B., Scherer, P.E., Ahima, R.S . Adiponectin acts in the brain to decrease body weight. Nat Med. 10:524 529, 2004. PMID15077108 4. Rajala, M.W., Qi, Y., Patel, H.R., Takahashi, N., Banerjee, R., Pajvani, U.B., Sinha, M.K., Gingerich, R.L., Scherer, P.E., Ahima, R.S. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 53:1671 1679, 2004. PMID15220189 5. Qi, Y., Nie, Z., Lee, Y.S., Singhal, N.S., Scherer, P.E., Lazar, M.A., Ahima, R.S . Loss of resistin improves glucose homeostasis in leptin deficiency. Diabetes 55:3083 3090, 2006. PMID17065346 6. Singhal, N.S., Lazar, M.A., Ahima, R.S . Central resistin induces hepatic insulin resistance via neuropeptide Y. J Neurosci 27:12924 12932, 2007. PMID18032666 7. Imai, Y., Varela, G.M., Jackson, M.B., Graham, M.J., Crooke, R.M., Ahima, R.S . Reduction of hepatosteatosis and lipid levels by an adipose differentiation related protein antisense oligonucleotide. Gastroenterology 132:1947 1954, 2007. PMID17484887 8. Singhal, N., Patel, R.T., Qi, Y., Lee, Y.S., Ahima, R.S.Loss of resistin ameliorates hyperlipidemia and hepatic steatosis in leptin deficient mice. Am J Physiol Endocrinol Metab 295:E331 338, 2008. PMC2519749 9. Akpan, I., Goncalves, M.D., Dhir, R., Yin, X., Pistilli, E.E., Bogdanovich, S., Khurana, T.S., Ucran, J., Lachey, J., Ahima, R.S. The effects of a soluble activin type IIB receptor on obesity and insulin sensitivity. Int J Obes (Lond) 33(11):1265 1273, 2009. PMID:19668253 10. Qatanani, M., Szwergold, N.R., Greaves, D.R., Ahima, R.S., Lazar, M.A. Macrophage derived human resistin exacerbates adipose tissue inflammation and insulin resistance in mice. J Clin Invest. 119:531 539, 2009. PMC2648673 11. Goncalves, M.D., Pistilli, E.E., Balduzzi, A., Birnbaum, M.J., Lachey, J., Khurana, T.S., Ahima, R.S . Akt deficiency attenuates muscle size and function but not the response to ActRIIB inhibition. PLoS One 5(9):e12707, 2010. PMID:20856813 12. Pistilli, E.E., Bogdanovich, S., Garton, F., Yang, N., Gulbin, J.P., Conner, J.D., Anderson, B.G., Quinn, L.S., North, K., Ahima, R.S., Khurana, T.S. Loss of IL 15 receptor α alters the endurance, fatigability, and metabolic characteristics of mouse fast skeletal muscles. J Clin Invest. 121:3120 32, 2011. PMID:21765213 13. Lee, E.B., Warmann, G., Dhir, R., Ahima, R.S. Metabolic dysfunction associated with adiponectin deficiency enhances kainic acid induced seizure severity. J Neurosci. 31(40):14361 14366, 2011. PMID:21976521 14. Carr, R.M., Patel, R.T., Rao, V., Dhir, R., Graham, M.J., Crooke, R.M., Ahima, R.S. Reduction of TIP47 improves hepatic steatosis and glucose homeostasis in mice. Am J Physiol Regul Integr Comp Physiol. 302(8):R996 1003, 2012. PMID:22378776 15. Sun, Z., Miller, R.A., Patel, R.T., Chen, J., Dhir, R., Wang, H., Zhang, D., Graham, M.J., Unterman, T.G., Shulman, G.I., Sztalryd, C., Bennett, M.J., Ahima, R.S., Birnbaum, M.J., Lazar, M.A. Hepatic Hdac3 promotes gluconeogenesis by repressing lipid synthesis and sequestration. Nat Med. 18:934 942, 2012.PMID:22561686