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.
Shen M, Schmitt S, Buac D, Dou QP. Targeting the ubiquitin-proteasome system for cancer therapy. Expert Opin Ther Targets. 2013;17:1091-108.
Kast RE, Boockvar JA, Brüning A, Cappello F, Chang WW, Cvek B, Dou QP, Duenas-Gonzalez A, Efferth T, Focosi D, Ghaffari SH, Karpel-Massler G, Ketola K, Khoshnevisan A, Keizman D, Magné N, Marosi C, McDonald K, Muñoz M, Paranjpe A, Pourgholami MH, Sardi I, Sella A, Srivenugopal KS, Tuccori M, Wang W, Wirtz CR, Halatsch ME. A conceptually new treatment approach for relapsed glioblastoma: coordinated undermining of survival paths with nine repurposed drugs (CUSP9) by the International Initiative for Accelerated Improvement of Glioblastoma Care. Oncotarget. 2013;4:502-30.
Zhang Z, Bi C, Buac D, Fan Y, Zhang X, Zuo J, Zhang P, Zhang N, Dong L, Dou QP. Organic cadmium complexes as proteasome inhibitors and apoptosis inducers in human breast cancer cells.Zhang Z, Bi C, Buac D, Fan Y, Zhang X, Zuo J, Zhang P, Zhang N, Dong L, Dou QP. J Inorg Biochem. 2013;123:1-10.
Huang H, Liu N, Yang C, Liao S, Guo H, Zhao K, Li X, Liu S, Guan L, Liu C, Xu L, Zhang C, Song W, Li B, Tang P, Dou QP, Liu J. HDAC inhibitor L-carnitine and proteasome inhibitor bortezomib synergistically exert anti-tumor activity in vitro and in vivo. PLoS One. 2012;7:e52576.
Li X, Liu S, Huang H, Liu N, Zhao C, Liao S, Yang C, Liu Y, Zhao C, Li S, Lu X, Liu C, Guan L, Zhao K, Shi X, Song W, Zhou P, Dong X, Guo H, Wen G, Zhang C, Jiang L, Ma N, Li B, Wang S, Tan H, Wang X, Dou QP, Liu J. Gambogic acid is a tissue-specific proteasome inhibitor in vitro and in vivo. Cell Rep. 2013;3:211-22..
Buac D, Shen M, Schmitt S, Kona FR, Deshmukh R, Zhang Z, Neslund-Dudas C, Mitra B, Dou QP. From Bortezomib to other Inhibitors of the proteasome and beyond. Curr Pharm Des. 2013;19:4025-38.
Zuo J, Bi C, Fan Y, Buac D, Nardon C, Daniel KG, Dou QP. Cellular and computational studies of proteasome inhibition and apoptosis induction in human cancer cells by amino acid Schiff base-copper complexes. Zuo J, Bi C, Fan Y, Buac D, Nardon C, Daniel KG, Dou QP. J Inorg Biochem. 2013;118:83-93.
Huang H, Liu N, Guo H, Liao S, Li X, Yang C, Liu S, Song W, Liu C, Guan L, Li B, Xu L, Zhang C, Wang X, Dou QP, Liu J.
L-carnitine is an endogenous HDAC inhibitor selectively inhibiting cancer cell growth in vivo and in vitro. PLoS One. 2012;7:e49062.
Chen D, Banerjee S, Cui QC, Kong D, Sarkar FH, Dou QP. Activation of AMP-activated protein kinase by 3,3'-Diindolylmethane (DIM) is associated with human prostate cancer cell death in vitro and in vivo. PLoS One. 2012;7:e47186.
Zhang Z, Bi C, Schmitt SM, Fan Y, Dong L, Zuo J, Dou QP. 1,10-Phenanthroline promotes copper complexes into tumor cells and induces apoptosis by inhibiting the proteasome activity. J Biol Inorg Chem. 2012;17:1257-67.
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;12:1193-201.
Education and Training:
PhD (1988): Rutgers University, New Jersey