Hari K. Bhat, Ph.D.
Assistant Professor of Environmental Health Sciences

Dr. Bhat’s research interests focus on the elucidation of biochemical and molecular mechanisms of hormonal carcinogenesis. Exogenous and endogenous exposure to estrogens is associated with the development of human cancers. Estrogen-mediated  carcinogenesis is speculated to result from a cumulative effect of hormonal effects and oxidative damage resulting from the metabolic activation of estrogens. Environmental insult may also play a crucial role in this carcinogenic process. The mechanism of hormonal carcinogenesis is being investigated using animal models and relevant cell lines. 

The research emphasis in Dr. Bhat’s laboratory is on defining the role of hormonal potency and estrogen metabolism in gene alteration and tumor development.  Some of the ongoing studies include to:

1)  Characterize the role of oxidant stress in differential gene expression in estrogen-induced carcinogenesis. Markers of free radical production and oxidative damage to DNA are being used to quantitate oxidative stress. Estrogens of different hormonal and metabolic activation potential are being used.

2)  Clone and characterize novel gene sequences differentially expressed in estrogen-induced tumors. Differential expression of novel genes has been shown in estrogen-induced carcinogenesis using animal models. Studies aimed at characterizing the relevance of differentially expressed genes to the phenotype of estrogen-induced neoplasia are in progress.

3)  Define damage to mitochondrial DNA as a marker of oxidative stress under conditions of environmental exposure. Damage to mitochondrial DNA has been associated with aging and implicated in several disease processes.

Results of these studies will be important in understanding of early molecular events that can potentially be the focus of therapeutic intervention to stem the progression of hormone-induced neoplasia.

Publications

Bhat, Hari K. and Vadgama, J.V. (2000) Hamster estrogen receptor cDNA: cloning and mRNA expression.  J. Steroid Biochem. Mol. Biol., 72, 47-53.

Bhat, Hari K.,  Hiatt, William R., Hoppel, Charles R., and Brass, Eric P. (1999) Skeletal muscle mitochondrial DNA injury in patients with unilateral peripheral arterial disease. Circulation 99, 807-812.

Bhat, Hari K., Han, X., Gladek, A. and Liehr, Joachim G. (1994)  Regulation of the formation of the major diethylstilbestrol-DNA adduct and some evidence of its structure.  Carcinogenesis, 15, 2137-2142.

Bhat, Hari K., Hacker, Hans J., Bannasch, P., Thompson, E.A. and Liehr, Joachim G.  (1993) Localization of estrogen receptors in interstitial cells of hamster kidney and in estradiol-induced renal tumors as evidence of  the mesenchymal origin of this neoplasm.   Cancer Res.  53, 5447-5451.