 Charles F. Kettering Professor of Medicine
Chief, Division of Endocrinology
Medical School
Columbia University College of Physicians, New York, NY
Residency
The Presbyterian Hospital, New York, NY
Endocrine Fellowships
Massachusetts General Hospital, Harvard Medical School, Boston, MA
Board Certified
American Board of Internal Medicine 1980;
Endocrinology and Metabolism 1983 Research Topics Genetic Analysis of Polycystic Ovary Syndrome (PCOS) Insulin Action and Secretion in PCOS Androgens and Insulin Action
The research themes of the Dunaif lab are the genetics of Polycystic Ovary Syndrome (PCOS), the cellular molecular mechanisms of insulin resistance and the mechanisms underlying the association between metabolism and reproduction. There are three major research projects currently ongoing. The approaches range from large-scale family studies through intensive patient-oriented research to animal models and cellular and molecular biology. PCOS is the human disease model. This syndrome is characterized by increased androgen biosynthesis and disordered gonadotropin secretion. It is among the most common endocrine disorders of women, the leading cause of hormonally-related infertility and a major risk factor for type 2 diabetes mellitus. The Genetic Basis of PCOS This research program focuses on identifying the susceptibility genes for PCOS, performing genotype-phenotype analyses and identifying environmental and genetic factors contributing to PCOS familial phenotypes. Studies include family studies with linkage analysis and detailed analyses of reproductive function and insulin action in women with PCOS and their relatives. The approaches include statistical genetics and in vivo studies of insulin action and secretion, as well as pulsatile gonadotropin secretion. A susceptibility gene region has been identified on chromosome 19 close to the insulin receptor gene. This research is supported by the NICHD National Cooperative Program for Infertility Research. Insulin Action and Secretion in PCOS These studies are focused on identifying the cellular and molecular mechanisms of defects in insulin action and secretion in PCOS. Approaches include detailed in vivo studies of these parameters utilizing techniques such as the euglycemic glucose clamp, frequently sampled intravenous glucose intolerance test with minimal model analysis and graded glucose infusions. Insulin receptor signal transduction is examined in human skeletal muscle biopsies, as well as in human skeletal muscle and adipocyte cultures. Intrinsic defects in insulin receptor signaling have been identified and the mechanisms of these abnormalities are currently under investigation. Androgens and Insulin Action These studies examine the impact of prenatal androgen exposure on insulin action in primate and sheep models. Studies include examination of lipolysis and insulin signaling in skeletal muscle and adipose tissue. Selected Publications since 2001 Fogel RB, A Malhotra, G Pillar, SD Pittman, A Dunaif, DP White. Increased prevalence of obstructive sleep apnea syndrome in obese women with polycystic ovary syndrome compared with controls. J Clin Endocrinol Metab 86:1175-1180, 2001 Rui L, V Aguirre, JK Kim, GI Shulman, A Lee, A Corbould, A Dunaif, MF White. Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. J Clin Invest 107:181-189, 2001 Dunaif A, E Diamanti-Kandarakis, A Lee, X Wu. Defects in insulin receptor signaling in vivo in the polycystic ovary syndrome (PCOS). Am J Physiol: Endocrinol Metab 281: E392-399, 2001 Legro RS, AR Kunselman, A Dunaif. Prevalence and predictors of dyslipidemia in women with polycystic ovary syndrome. Am J Med 111:607-13, 2001 Solomon CG, FB Hu, A Dunaif, J Rich-Edwards, WC Willett, DJ Hunter, GA Colditz, FE Spiezer, JE Manson. Long or highly irregular menstrual cycles as a predictor of type 2 diabetes Mellitus: a prospective study. JAMA 286:2421-6, 2001 Solomon CG, FB Hu, A Dunaif, JE Rich-Edwards, MJ Stampfer, WC Willett, FE Speizer, JE Manson. Menstrual cycle irregularity and risk for future cardiovascular disease. J Clin Endocrinol Metab 87: 2013-17, 2002 Palmert MR, CM. Gordon, A Kartashov, RS Legro, S.J Emans, A Dunaif. Screening for abnormal glucose tolerance in adolescents with polycystic ovary syndrome. J Clin Endocrinol Metab 87:1017-1023, 2002 Legro RS, AR Kunselman, L Demers, SC Wang, R Bentley-Lewis, A Dunaif. Elevated dehydroepiandrosterone sulfate levels as the reproductive phenotype in the brothers of women with polycystic ovary syndrome. J Clin Endocrinol Metab 87: 2134-38, 2002 Legro RS, R Bentley-Lewis, D Driscoll, S Wang, A Dunaif. Insulin resistance in the sisters of women with polycystic ovary syndrome: association with hyperandrogenemia rather than menstrual irregularity. J Clin Endocrinol Metab 87: 2128-33, 2002 Legro RS, Urbanek M, Kunselman AR, Leiby BE, A Dunaif. Self-selected women with polycystic ovary syndrome are reproductively and metabolically abnormal and undertreated. Fertility & Sterility 78: 51-57, 2002 Li M, JF Youngren, A Dunaif, ID Goldfine, BA Maddux, BB Zhang, JL Evans. Decreased Insulin Receptor Autophosphorylation in Fibroblasts from Patients with PCOS: Effects of Serine Kinase Inhibitors and Insulin Receptor Activators. J Clin Endocrinol Metab 87: 4088-4093, 2002 Urbanek M, Du Y, Silander, Collins FS, Steppan CM, Strauss JR, A Dunaif , Spielman RS, Legro RS. Variation in resistin gene promoter not associated with polycystic ovary syndrome (PCOS). Diabetes 52:214-217, 2003 Jabara S, Christenson LK, Wang CY, McCallister JM, Javitt NB, A Dunaif, Strauss JF. Stromal cells of the human postmenopausal ovary display a distinctive biochemical and molecular phenotype. J Clin Endocrinol Metab 88:484-492, 2003 Sam S, Dunaif A. Polycystic ovary syndrome: syndrome XX? Trends Endocrinol Metab. 2003;8:365-70. Dunaif A. Hyperandrogenemia is necessary but not sufficient for polycystic ovary syndrome. Fertil Steril 2003;2:262-3.
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