Office Address

Karmanos Cancer Institute
HWCRC - 611
4100 John R.
Detroit, 48201

 

Position Title

Professor

Biography

The main objective in this laboratory is aimed at discovering molecular targets of chemopreventive agents in pre-clinical studies, followed by validation in targeted cancer prevention clinical trials. Dr. Dou's laboratory is one of the first to report that proteasome inhibitors rapidly induce tumor cell apoptosis, selectively activate the cell death program in oncogene-transformed, but not normal or untransformed cells, and are able to trigger apoptotic death in human cancer cells that are resistant to various anticancer agents. Possible molecular mechanisms involve, at least in part, accumulation of the cyclin-dependent kinase inhibitor p27kip and the apoptosis inducer Bax. In addition, Dr. Dou and his colleagues have shown that proteasome inhibitors suppress human tumor growth in nude mice. Recently, Dr. Dou's laboratory has shown that some tea polyphenols and soy isoflavones potently and specifically inhibit the chymotrypsin-like activity of the proteasome in vitro and in vivo at physiological concentrations. Furthermore, his laboratory has established, for the first time, a computational molecular model that shows how tea polyphenols or soy isoflavones bind and target the proteasome beta5 subunit. This innovative computational model has been validated by comparison of predicted and actual activities of tea polyphenol analogs, either naturally occurring or rationally designed and synthesized. The future targeted prevention trials have been planned to examine whether polyphenols or isoflavones selectively inhibit proteasome activity in human cancer cells and whether such inhibitory activities correlate with clinical effects seen in serum and tissue samples as well as the potential involvement of genetic and environmental risk factor

Education Training

Ph.D., Rutgers University, 1988

Areas of Interest

Cancer Control and Prevention

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