Todd Leff (ak3067)

Lab: Integrative Biosciences Center
6135 Woodward Avenue
Detroit, MI 48202
(313)577-3006 

Graduate School: Maccabees Building, rm. 6305.5
5057 Woodward Avenue
Detroit, MI 48202
(313)577-8002

Associate Dean, Graduate School
Associate Professor, Pathology
Wayne State University

Gene transcription, nuclear receptors, metabolic regulation, insulin resistance, and diabetes

1. Hong YH, Varanasi US, Yang W and Leff T, 2003, AMP-activated protein kinase regulates HNF4α transcriptional activity by inhibiting dimmer formation and decreasing protein stability, J Biol Chem, 278: 27495-501.
2. Hegele RA and Leff T, 2004, Unbuckling lipodystrophy from insulin resistance and hypertension, J Clin Invest, 114: 163-5.
3. Li G & Leff T, 200, Altered promoter recycling rates contribute to dominant/negative activity of human PPAR γ mutations associated with diabetes,  Mol Endocrinol, 21:  857-64.
4. Monajemi H, Zhang L, Li G, Cao H, Maas M, Brouwer CB, Kalkhoven E, Stroes E, Hegele RA, and Leff T, 2007, Familial partial lipodystrophy phenotype resulting from a single-base mutation in DNA binding domain of peroxisome proliferator-activated receptor gamma,  J Clin Endocrinol Metab, 92: 1606-12.
 

As an associate dean of the Graduate School, Dr. Leff oversees the review of new graduate programs and the Postdoc to Faculty Transition program. Dr. Leff is also the director of the Ph.D. program in the department of pathology at the School of Medicine.

Dr. Leff joined the Wayne State faculty in 2012. His research is focused on the molecular biology of diabetes and obesity, and on the effects of environmental contaminants on metabolic health.

Education
Ph.D. (1982): Indiana University, Bloomington, IN, USA

Postdoctoral Fellowship
1982-1985: Universite Louis Pasteur, Strasbourg, France

Dr. Leff's research interest is the regulation of gene expression by metabolic and nutritional signals. The laboratory of Dr. Leff is focused on understanding the molecular mechanism that underlie the metabolic diseases of diabetes and obesity, and in deciphering the role that gene expression plays in both the etiology and treatment of these diseases. Specific areas of focus are the molecular biology of two transcription factors whose activity is specifically regulated by metabolic and nutritional signals - the nuclear receptors PPARγ and HNF4α. The work on PPARγ seeks to identify the mechanism by which it regulates insulin sensitivity and glucose homoeostasis. HNF4α regulates many genes of metabolic significance and this work is directed toward understanding how its activity is regulated by upstream kinases, especially AMP-activated protein kinase. Additional areas of interest are the suppression of diabetic cardiomyopathy by the hormone adiponectin and the effect of environmental toxicants on the expression of metabolic genes.

Regulation of gene expression by metabolic and nutritional signals; Molecular biology of type 2 diabetes; Role of the nuclear receptors (PPARγ; HNF4α) in regulating cellular and whole body metabolism; Effect of environmental toxicants on susceptibility to metabolic diseases