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| Meet the Staff
Dr. Qinghong Zhang, PhD Title:
Assistant Professor (Vollum Institute, Oregon Cancer Institute)
Department:
Radiation Medicine
Specialty:
Radiation Medicine
Research:
Cancer therapy has progressed tremendously over the decades. Yet, its success has been overshadowed by radiation/chemo resistance that is intrinsically associated with malignancy. The development of strategies and targets to specifically sensitize cancer cells to current therapy is urgently needed. The inactivation of p53, which occurs in majority of human cancer, has been experimentally demonstrated and clinically associated with the development of the resistance to radiation therapy and chemotherapy. Therefore, the development of therapeutic strategy in treating cancers with defective p53 has attracted major efforts in the cancer research field. In the past few years, my lab has been working on the apoptotic pathway mediated by CtBP, a transcriptional co-repressor sensitive to cellular redox status. We have demonstrated that CtBP down-regulation triggers p53-independent apoptosis in tumor cells. Currently, my research is focused on the characterization of the apoptotic pathway mediated by CtBP inactivation in attempt to develop strategies and targets for cancer therapy.
My lab has been focusing on the identification of signal transduction pathways that regulate CtBP. By using a repressor:CtBP co-complex as bait, we have successfully identified HIPK2 as a critical CtBP modulator. We have demonstrated that HIPK2-triggered CtBP clearance is providing alternative/complement pathways for UV-induced apoptosis in tumor cells that lack p53. Recently, my lab has also shown that activation of the JNK1 pathway induces CtBP degradation and triggers p53-independent apoptosis in human cancer cells. In addition, we have shown that CtBP is subjected to poly-ubiquination and proteaosomal degradation after its phosphorylation by HIPK2 and/or JNK1. Both pathways could be therapeutically important in activating the pro-apoptotic genes that are normally repressed by CtBP.
The accumulated evidence has suggested that CtBP is a hub to regulate apoptosis from variety of stress signals including JNK and HIPK2 activation independently of p53. A close interaction with clinicians will help us to translational research. We will extend our research to establish the relevance to clinical oncology. The long-term goal of our research is to develop translational studies for targeted cancer therapy based on the findings of the above basic research. These targeted therapies will initially be tested in animal models and then move to clinical trials in collaboration with oncologists.
Current Grant Funding:
1R01CA115468-01A2 (08/01/2007-07/31/2012)
NIH/NCI
UV regulation of anti-apoptotic co-repressor CtBP
Selected Publications:
'Metabolic regulation of SIRT1 transcription via a HIC1:CtBP co-repressor complex'. Zhang Q, Wang SY, Fleuriel C, Leprince D, Rocheleau JV, Piston DW, and Goodman RH. Proc. Natl. Acad. Sci. U S A. 2007 104:829-33 [http://www.pnas.org/cgi/content/abstract/104/3/829]
'C-Jun NH2-terminal kinase promotes apoptosis by down-regulating the transcriptional co-repressor CtBP'. Wang SY, Iordanov I, and Zhang Q. J. Biol. Chem. 2006 281:34810-5 [http://www.jbc.org/cgi/content/abstract/281/46/34810]
'Redox senspr CtBP mediates hypoxia-induced tumor cell migration'. Zhang Q, Wang SY, Nottke AC, Rocheleau JV, Piston DW, and Goodman RH. Proc. Natl. Acad. Sci. U S A. 2006 103:9029-33 [http://www.pnas.org/cgi/content/abstract/103/24/9029]
'Homeodomain interacting protein kinase 2 mediates CtBP phosphorylation and degradation in UV-triggered apoptosis'. Zhang Q, Nottke A, and Goodman RH. Proc. Natl. Acad. Sci. U S A. 2005 102:2802-7 [http://www.pnas.org/cgi/content/abstract/102/8/2802]
'Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP'. Zhang Q, Yoshimatsu Y, Hildebrand J, Frisch SM, and Goodman RH. Cell 2003 115:177-86 [http://www.cell.com/content/article/abstract?uid=PIIS009286740300802X]
'C-terminal-binding protein corepresses epithelial and proapoptotic gene expression programs'. Proc. Grooteclaes M, Deveraux Q, Hildebrand J, Zhang Q, Goodman RH, and Frisch SM. Natl. Acad. Sci. U S A. 2003 100:4568-73 [http://www.pnas.org/cgi/content/abstract/100/8/4568]
'Regulation of corepressor function by nuclear NADH'. Zhang Q, Piston DW, and Goodman RH. Science. 2002 Mar;295:1895-7 [http://www.sciencemag.org/cgi/content/abstract/295/5561/1895]
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