Alumnus Speaker at the 2004 MSTP Retreat

Jose Florez, M.D., Ph.D.

I graduated from the Medical Scientist Training Program at Northwestern University in 1997 and was the Alumni Speaker at the 2004 MSTP Retreat on October 29-31, 2004. I graduated from the combined B.A./M.S. Honors Program at Northwestern University in 1988 and then entered the Medical Scientist Training Program at Northwestern University . During my Ph.D. work with Joe Takahashi, I conducted a proteomic screen looking for circadian proteins in the chick pineal gland and identified one protein whose levels of expression cycled in a circadian manner. Through microsequencing and two-dimensional Western blotting, we identified it as tryptophan hydroxylase, the first enzyme in the melatonin synthetic pathway. We next described its regulation by both light and pharmacological agents, cloned the gene and demonstrated a circadian oscillation in its protein and mRNA levels. After obtaining M.D./Ph.D. degrees, I moved to Boston in 1997 where I had matched as a preliminary medical intern at the Massachusetts General Hospital , with the intention to seek residency training in neurology. After one year in the combined Partners Neurology program, I returned to the internal medicine residency at MGH and completed fellowship training in endocrinology. Since 2002 I have been working with David Altshuler on the genetics of type 2 diabetes, with particular attention to genes that encode hypoglycemic drug targets. Currently I am an Instructor at Harvard Medical School and Clinical Assistant in the Diabetes Unit at the Massachusetts General Hospital.

Research Interests

By characterizing the haplotype structure of the genes encoding the sulfonylurea receptor and the islet ATP-sensitive potassium channel Kir6.2, I have confirmed that the E23K polymorphism in Kir6.2 is associated with type 2 diabetes and affects measures of insulin secretion in humans. I have also shown that, in contrast to previous reports, G972R polymorphism in the insulin receptor substrate 1 is unlikely to play a significant role in the pathogenesis of type 2 diabetes. Currently I am pursuing similar approaches in the seven AMP kinase genes (the drug target for metformin), by genotyping the participants of the Diabetes Prevention Program.

I amcurrently an Instructor at Harvard Medical School and a Clinical Assistant in the Diabetes Unit at the Massachusetts General Hospital. I have authored 8 peer-reviewed original publications, 5 review papers and 6 book chapters and serve as a reviewer for several endocrine journals. I am the recipient of a K23 Research Career Development Award from the NIH.

Recent Publications

Florez, J.C. 2004. Phenotypic consequences of the peroxisome proliferator-activated receptor-gamma Pro12Ala polymorphism: the weight of the evidence in genetic association studies. J Clin Endocrinol Metab. 89(9):4234-7.

Florez JC, Burtt N, de Bakker PI, Almgren P, Tuomi T, Holmkvist J, Gaudet D, Hudson TJ, Schaffner SF, Daly MJ, Hirschhorn JN, Groop L, Altshuler D. 2004.Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 53(5):1360-8.

Florez JC, Hirschhorn J, Altshuler D. 2003.The inherited basis of diabetes mellitus: implications for the genetic analysis of complex traits. Annu Rev Genomics Hum Genet. 4:257-91.