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Qi-En Wang, MD, PhD


Qi-En Wang, MD, PhD
Assistant Professor
Division of Radiobiology
Department of Radiology
1014 Biomedical Research Tower
460 W. 12th Ave.
Columbus, OH 43210
Phone: 614-292-9021
Fax: 614-292-9102
E-mail: qi-en.wang@osumc.edu
 
The focus of our research is on the regulation of DNA repair in the context of chromatin, and the connection of DNA repair to cancer therapy. Our group has identified several post-translational modifications of DNA repair factors, and is carrying out studies to elucidate their function in the efficient DNA repair process. Meanwhile, we applied our DNA repair expertise to the study of chemotherapy resistance of cancer stem cells (CSC). We have identified DNA polymerase eta-mediated translesion DNA synthesis (TLS), a DNA damage tolerance mechanism that bypasses DNA damage during replication, plays a crucial role in the survival of CSCs after cisplatin treatment, and might be a key factor responsible for tumor relapse and the development of acquired cisplatin resistance. We have also identified a new function of a DNA repair factor, named damaged DNA binding protein 2 (DDB2), in suppressing tumorigenicity of ovarian cancer cells by limiting the CSC population. A comprehensive investigation is currently being carried out to understand the underlying mechanism. Our overall goal is to understand the molecular mechanism underlying genomic instability and chemotherapy resistance to DNA-damaging agents. Ultimately, we hope to translate this knowledge into new strategies for improving the efficacy of platinum-based chemotherapy, and facilitating the eradication of CSCs, leading to an overcome of chemotherapy resistance and tumor relapse.
 
Research Interest
Cancer stem cell
DNA damage repair
Chemotherapy resistance and tumor relapse
 
Team members
Amit Kumar Srivastava, PhD, Postdoc Fellow
Tiantian Cui, PhD, MD, Postdoc Fellow
Meihua Qu, PhD, Visiting scholar
Ning Zou, PhD, MD, Visiting scholar
Asim Rizvi, MS, Visiting PhD student
 
Selected Publications
 
1.        Srivastava AK, Han C, Zhao R, Cui T, Dai Y, Mao H, Zhao W, Zhang X, Yu J, Wang QE. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells. Proc Natl Acad USA. 2015 Mar 23; Published ahead of print. 
2.        Cui T, Srivastava AK, Han C, Yang L, Zhao R, Zou N, Qu M, Duan W, Zhang X, Wang QE. XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression. Oncotarget 2015; Advance Publication.
3.        Qian J, Pentz K, Zhu Q, Wang Q, He J, Srivastava AK, Wani AA. USP7 modulates UV-induced PCNA monoubiquitination by regulating DNA polymerase eta stability. Oncogene. 2014 Dec; Epub ahead of print.
4.        Han C, Zhao R, Liu X, Srivastava A, Gong L, Mao H, Qu M, Zhao W, Yu J, Wang QE. DDB2 suppresses tumorigenicity of ovarian cancer cells by limiting the cancer stem cell population. Mol Cancer Res. 2014 May; 12(5): 784-794.
5.        Zhao R, Han C, Eisenhauer E, Kroger J, Zhao W, Yu J, Selvendiran K, Liu X, Wani AA, Wang QE. DNA damage-binding complex recruits HDAC1 to repress Bcl-2 transcription in human ovarian cancer cells. Mol Cancer Res. 2014 Mar; 12(3): 370-380.
6.        He J, Zhu Q, Wani G, Sharma N, Han C, Qian J, Pentz K, Wang QE, Wani AA. Ubiquitin-specific protease 7 regulates nucleotide excision repair through deubiquitinating XPC protein and preventing XPC protein from undergoing ultraviolet light-induced and VCP/p97 protein-regulated proteolysis. J Biol Chem. 2014 Sep; 289(39): 27278-27289.
7.        Wang QE, Han C, Zhang B, Sabapathy K, Wani AA. Nucleotide excision repair factor XPC enhances DNA damage-induced apoptosis by downregulating the anti-apoptotic short isoform of caspase-2. Cancer Res. 2012 Feb; 72(3): 666-675.
8.        Wang QE,  Prætorius-Ibba M, Zhu Q, El-Mahdy MA, Wani G, Zhao Q, Qin S, Patnaik S, and Wani AA. Ubiquitylation-independent degradation of Xeroderma pigmentosum group C protein is required for efficient nucleotide excision repair. Nucleic Acids Res. 2007 Aug; 35(16): 5338-5380.
9.        Wang QE, Zhu Q, Wani G, El-Mahdy MA, and Wani AA. DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation, Nucleic Acids Res. 2005 Jul; 33(13): 4023-4034.
10.      Wang QE, Han C, Zhao R, Wani G, Zhu Q, Gong L, Battu, Racoma I, Sharma N, Wani AA. p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair. Nucleic Acids Res. 2013 Feb; 41(3): 1722-1733.