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Q. Ping Dou, Ph.D.
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RESEARCH INTERESTS:
The main objective in this laboratory is aimed at discovering molecular targets of nature products in pre-clinical studies, followed by validation in targeted cancer intervention 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. Dr. Dou's laboratory has also shown that some tea polyphenols and medicinal compounds 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 these natural compounds bind and target the proteasome chymotrypsin subunit. This innovative computational model has been validated by comparison of predicted and actual activities of various analogs, either naturally occurring or rationally designed and synthesized. Recently, Dr. Dou and collaborators have reported that (i) some old copper-binding drugs (such as the antialcoholism drug Disulfiram) could converting the pro-angiogenic copper to a specific cancer cell death inducer, (ii) Disulfiram also promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells, and (iii) environmental toxic organotins target the proteasome in human cells and proteasome inhibition by organotins contributes to their cellular toxicity.
Current Lab Personnel:
Di Chen, Ph.D., Res Assistant Professor
Mike Frezza, Post-Doctoral Fellow
Min Shen, Graduate Student
Sara Schmitt, Graduate Student
Taskeen Mujtaba, Graduate Student
Cindy (Qiuzhi) Cui, Research Assistant
Jyoti Kanwar, Research Assistant
Jingchun Liu, Research assistant
Li Lu, Ph.D., Visiting Scholar
Carol Maconochie, Adm Assistant
Publications:
Yang HJ, Chen D, Cui QC, Yuan X, and Dou QP. Celastrol, a triterpene extracted from the Chinese Thunder of God Vine, is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice. (A figure was selected as the cover of the issue) Cancer Research 66, 4758-4765, May 1, 2006.
Chen D, Cui QC, Yang HJ, and Dou QP. Disulfiram, A Clinically Used Anti-Alcoholism Drug and Copper-Binding Agent, Induces Apoptotic Cell Death in Breast Cancer Cultures and Xenografts via Inhibition of the Proteasome Activity. Cancer Research 66, 10425-10433, 2006.
Landis-Piwowar KR, Huo CD, Chen D, Cui QC, Minic V, Shi GQ, Chan TH, and Dou QP. A Novel Pro-drug of the Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate as a Potential Anti-Cancer Agent. Cancer Res 67: 4303-4310, 2007.
Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar A, and Dou QP. Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo Cancer Research 2008;68(18):7283-92.
Milacic V and Dou QP. The tumor proteasome as a novel target for gold(III) compounds: implications in breast cancer therapy (invited review). Coordination Chemistry Reviews (Impact Factor 10.566, 2006), 2009; 253:1649-1660.
http://pathology.med.wayne.edu/profile.php?id=42909
