W. Scott Moye-Rowley, Ph.D.

Professor and Executive Associate Head

Faculty Member: Holden Comprehensive Cancer Center
Faculty Member: Molecular and Cellular Biology Graduate Program

Purdue University, 1986

Research Interests

Our laboratory has two primary research interests centered on transcriptional control of gene expression. The first involves the study of the function of a yeast transcriptional regulatory protein. This yeast protein was designated Yap1p by virtue of its homology with a mammalian proto-oncoprotein, c-Jun. c-Jun is a component of a complex DNA binding activity present in animal cells referred to as AP-1. We have constructed yeast strains in which the normal YAP1 gene has been deleted. These yap1 mutant yeast cells were found to be hypersensitive to oxidative stress agents. Additionally, it has been found that transcriptional activity of Yap1p is stimulated by oxidative stress. We are dissecting the molecular events that lead to the activation of Yap1p function using a combination of genetics, molecular biology and biochemistry. The second area of investigation concerns the ability of particular mutant strains of yeast to simultaneously acquire resistance to several cytotoxic drugs with unrelated actions. This phenomenon, called pleiotropic drug resistance (Pdr) in yeast, is related to the multidrug resistance phenotype shown by mammalian tumor cells. Multidrug resistance is a major problem in chemotherapeutic treatment of cancer patients. We will use Pdr in yeast as a model for the mammalian phenotype to gain insight into the molecular events involved in eliciting multidrug resistance.

Representative References

1. Shahi, P., Gulshan, K. and Moye-Rowley W.S. Negative transcriptional regulation of multidrug resistance gene expression by an Hsp70 protein. J. Biol. Chem. 282: 26822-26831, 2007.

2. Panwar S.L. and Moye-Rowley W.S. Long chain base tolerance in Saccharomyces cerevisiae is induced by retrograde signals from the mitochondria. J Biol Chem. 281: 6376-6384, 2006.

3. Gulshan, K., Rovinsky, S.A., Coleman, S.T. and Moye-Rowley, W.S. Oxidant-specific folding of Yap1p regulates both transcriptional activation and nuclear localization. J Biol Chem. 280: 40524-40533, 2005.