Q. Ping Dou
Q. Ping Dou, Ph.D.
540.1 Hudson Webber
4100 John R. Road
Detroit, MI 48201
Mentoring: Richard Arkwright ( Year 4 )
Cancer Targeted Therapy, and Chemoprevention
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.
Chen X, Shi X, Zhao C, Li X, Lan X, Liu S, Huang H, Liu N, Liao S, Zang D, Song W, Liu Q, Carter BZ, Dou QP, Wang X, Liu J. Anti-rheumatic agent auranofin induced apoptosis in chronic myeloid leukemia cells resistant to imatinib through both Bcr/Abl-dependent and -independent mechanisms. Oncotarget. 2014 Aug 22. [Epub ahead of print]
Dou QP, Zonder JA. Overview of Proteasome Inhibitor-Based Anti-cancer Therapies: Perspective on Bortezomib and Second Generation Proteasome Inhibitors versus Future Generation Inhibitors of Ubiquitin-Proteasome System. Curr Cancer Drug Targets. 2014;14:517-36.
Dou QP. Editorial: recent advances in proteasome inhibitor-based cancer therapies. Curr Cancer Drug Targets. 2014;14:505.
Zhang P, Bi C, Schmitt SM, Li X, Fan Y, Zhang N, Dou QP. Metal-based 2,3-indolinedione derivatives as proteasome inhibitors and inducers of apoptosis in human cancer cells. Int J Mol Med. 2014;34:870-9.
Liu N, Liu C, Li X, Liao S, Song W, Yang C, Zhao C, Huang H, Guan L, Zhang P, Liu S, Hua X, Chen X, Zhou P, Lan X, Yi S, Wang S, Wang X, Dou QP, Liu J. A novel proteasome inhibitor suppresses tumor growth via targeting both 19S proteasome deubiquitinases and 20S proteolytic peptidases. Sci Rep. 2014;4:5240.
Huang H, Hua X, Liu N, Li X, Liu S, Chen X, Zhao C, Lan X, Yang C, Dou QP, Liu J. Anacardic acid induces cell apoptosis associated with induction of ATF4-dependent endoplasmic reticulum stress. Toxicol Lett. 2014;228:170-8.
Neslund-Dudas C, Levin AM, Beebe-Dimmer JL, Bock CH, Nock NL, Rundle A, Jankowski M, Krajenta R, Dou QP, Mitra B, Tang D, Rebbeck TR, Rybicki BA. Gene-environment interactions between JAZF1 and occupational and household lead exposure in prostate cancer among African American men.Cancer Causes Control. 2014;25:869-79.
Cheriyan VT, Wang Y, Muthu M, Jamal S, Chen D, Yang H, Polin LA, Tarca AL, Pass HI, Dou QP, Sharma S, Wali A, Rishi AK. Disulfiram suppresses growth of the malignant pleural mesothelioma cells in part by inducing apoptosis. PLoS One. 2014;9:e93711.
Neslund-Dudas C, Levin AM, Rundle A, Beebe-Dimmer J, Bock CH, Nock NL, Jankowski M, Datta I, Krajenta R, Dou QP, Mitra B, Tang D, Rybicki BA. Case-only gene-environment interaction between ALAD tagSNPs and occupational lead exposure in prostate cancer. Prostate. 2014;74:637-46.
Tomco D, Schmitt S, Heeg MJ, Dou QP, Verani CN. Inhibition of the 26S proteasome as a possible mechanism for toxicity of heavy metal species. J Inorg Biochem. 2014;132:96-103.
Metcalf R, Scott LM, Daniel KG, Dou QP. Proteasome inhibitor patents (2010 - present). Expert Opin Ther Pat. 2014;24:369-82.
Buac D, Kona FR, Seth AK, Dou QP. Regulation of metformin response by breast cancer associated gene 2. Neoplasia. 2013;15:1379-90.
Nardon C, Schmitt SM, Yang H, Zuo J, Fregona D, Dou QP. Gold(III)-dithiocarbamato peptidomimetics in the forefront of the targeted anticancer therapy: preclinical studies against human breast neoplasia. PLoS One. 2014;9:e84248.
Neslund-Dudas C, Kandegedara A, Kryvenko ON, Gupta N, Rogers C, Rybicki BA, Dou QP, Mitra B. Prostate tissue metal levels and prostate cancer recurrence in smokers. Biol Trace Elem Res. 2014;157:107-12.
Liu N, Huang H, Liu S, Li X, Yang C, Dou QP, Liu J. Calcium channel blocker verapamil accelerates gambogic acid-induced cytotoxicity via enhancing proteasome inhibition and ROS generation. Toxicol In Vitro. 2014 Apr;28(3):419-25.
Shi X, Chen X, Li X, Lan X, Zhao C, Liu S, Huang H, Liu N, Liao S, Song W, Zhou P, Wang S, Xu L, Wang X, Dou QP, Liu J. Gambogic acid induces apoptosis in imatinib-resistant chronic myeloid leukemia cells via inducing proteasome inhibition and caspase-dependent Bcr-Abl downregulation. Clin Cancer Res. 2014;20:151-63.
Liu N, Huang H, Xu L, Hua X, Li X, Liu S, Yang C, Zhao C, Zhao C, Li S, Dou QP, Liu J. The combination of proteasome inhibitors bortezomib and gambogic acid triggers synergistic cytotoxicity in vitro but not in vivo. Toxicol Lett. 2014;224:333-40.
Shen M, Zhang Z, Ratnam M, Dou QP. The interplay of AMP-activated protein kinase and androgen receptor in prostate cancer cells. J Cell Physiol. 2014;229:688-95
Education and Training:
PhD (1988): Rutgers University, New Jersey