Q. Ping Dou
Q. Ping Dou, Ph.D.
Professor
540.1 Hudson Webber
4100 John R. Road
Detroit, MI 48201
313-576-8301
doup@karmanos.org
Mentoring: Daniela Buac (Year 4), Sara Schmitt (Year 4)
Research Interests:
Cancer Targeted Therapy, and Chemoprevention
Research Description:
The main objective in this laboratory is to discover molecular targets of natural 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 certain copper-binding drugs (such as the antialcoholism drug Disulfiram) can convert the pro-angiogenic copper to a specific cancer cell death inducer. Disulfiram also promotes the conversion of carcinogenic cadmium to a proteasome inhibitor with pro-apoptotic activity in human cancer cells. Finally, environmental toxic organotins target the proteasome in human cells and proteasome inhibition by organotins contributes to their cellular toxicity.
Selected Publications:
Buac D, Schmitt S, Ventro G, Kona FR, Dou QP. Dithiocarbamate-Based Coordination Compounds As Potent Proteasome Inhibitors in Human Cancer Cells. Mini Rev Med Chem. 2012 Aug 27. [Epub ahead of print]
Zuo J*, Schmitt S*, Prakash J, Fan YH, Bi CF, Kodanko JJ, and Dou QP. Novel polypyridyl chelators deplete cellular zinc and destabilize the X-linked inhibitor of apoptosis protein prior to induction of apoptosis in human prostate and breast cancer cells. J Cell. Biochem. 2012 Aug;113(8):2567-75. doi: 10.1002/jcb.24132.
Schmitt S, Frezza M, and Dou, QP. New applications of old metal-binding drugs in the treatment of human cancer. In Special Issue entitled New Strategies in the detection, prevention and treatment of cancer, the Frontiers in Bioscience, 2012 Jan 1;4:375-391.
Frezza M, Schmitt S, Dou QP. Targeting the Ubiquitin-Proteasome Pathway: An Emerging Concept in Cancer Therapy (invited review). Curr Top Med Chem. 2011 Aug 9. [Epub ahead of print].
Frezza M, Yang H, and Dou QP. Modulation of the tumor cell death pathway by androgen receptor in response to cytotoxic stimuli. J Cell. Physiol. 2011. Nov;226(11):2731-9. PMCID: PMC3134581
Chen D and Dou QP. The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci. 2010 Sep 1;11(6):459-70.
Frezza M, Hindo S, Chen Di, Davenport A, Schmitt S, Tomco D, Dou QP. Novel Metals and Metal Complexes as Platforms for Cancer Therapy. Curr Pharm Des. 2010 Jun;16(16):1813-25.
Chen D, Milacic V, Frezza M, and Dou QP. Metal complexes, their cellular targets and potential for cancer therapy. Curr Pharm Des. 2009;15(7):777-91.
Milacic V and Dou QP. The tumor proteasome as a novel target for gold(III) compounds: implications in breast cancer therapy. Coordination Chemistry Reviews 2009; 253:1649-1660. PMCID: PMC2675785
Dou QP. Molecular Mechanisms of Green Tea Polyphenols. Nutrition and Cancer. 2009;61(6):827-35.
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 Sep 15;68(18):7283-92. PMCID: PMC2556983
Education and Training:
PhD (1988): Rutgers University, New Jersey