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Qi-en Wang 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

Research Interest:
     Research over the past years has provided ample evidence that genome instability is one of the main forces driving the onset and progression of carcinogenesis. Eukaryotic cells have developed a wide range of DNA repair pathways in order to maintain genomic stability and cell viability when exposed to environmental and endogenous metabolic DNA damaging agents. Different kinds of DNA damage need different DNA repair pathways, which function to remove and fix the DNA lesions in a timely manner to prevent the conversion of lesions into permanent mutations in the genome. Dysfunction of components involved in these processes contributes to genomic instability, which in turn leads to tumorigenesis. Therefore, activation of DNA repair pathway is very important to maintain genomic stability, while turning off DNA repair pathway might be also important, in particular, for chemotherapy with DNA damaging agents, such as cisplatin. The focus of our research is on the regulation of nucleotide excision repair (NER) in the context of chromatin, and the connection of DNA repair to cancer therapy. Most recently our work has come to focus on DNA damage response in human cancer stem cells (CSCs), and their contribution to the development of chemotherapy resistance.
     Cisplatin has been widely used for more than a generation to treat various malignant tumors, including ovarian, testicular, head and neck, and lung cancers. Chemotherapy with cisplatin is initially effective for most patients. However, the majority eventually becomes refractory to cisplatin treatment. Indeed, 90% of the deaths from ovarian cancer can be attributed to drug resistance. Poor understanding of the underlying mechanisms of this acquired drug resistance poses a critical cancer research challenge. Our research strives to explore the mechanisms underlying acquired cisplatin resistance. The focus of our research is on DDB2-mediated apoptosis and the role of CSCs and their genomic instability in the development of acquired cisplatin resistance.

Education:
1992-1997  Beijing Medical University, Beijing, China, Ph.D. in Occupational Health and Toxicology
1987-1992  Shanxi Medical College, Taiyuan, China, M.D. Equivalent

Academic Positions:

10/2011-present Assistant Professor (tenure-track), Division of Radiobiology, Department of Radiology, The Ohio State University               
10/2007-09/2011 Assistant Professor (research-track), Division of Radiobiology, Department of Radiology, The Ohio State University
05/2006-09/2007 Research Scientist, Division of Radiobiology, Department of Radiology, The Ohio State University
04/2004-04/2006 Research Associate 2 B/H, Division of Radiobiology, Department of Radiology, The Ohio State University        
09/2001-03/2004 Research Associate 1 B/H, Division of Radiobiology, Department of Radiology, The Ohio State University
06/2000-08/2001 Associate Professor, Department of Occupational and Environmental Health Science, School of Public Health, Peking University, Beijing, China.        
08/1997-05/2000 Instructor, Department of Occupational Health, School of Public Health, Beijing   Medical University, Beijing, China.

Recent Publications:
1. Zhao R, Han C, Eisenhauer E, Kroger J. Zhao W, Yu J, Karuppaiyah S, Liu X, Wani AA, and Wang QE*. (2013) DNA damage-binding complex recruits HDAC1 to repress Bcl-2 transcription in human ovarian cancer cells. Mol Cancer Res. In revision (*: Correspondence author).
2. Han C, Zhao R, Kroger J, Qu M, Wani AA, Wang QE*. (2013) Caspase-2 short isoform interacts with membrane-associated cytoskeleton proteins to inhibit apoptosis. PLoS One 8: e67033 (*: Correspondence author).
3. Yu J, Peng Y, Wu LC, Xie Z, Deng Y, Hughes T, He S, Mo X, Chiu M, Wang QE, He X, Liu S, Grever MR, Chan KK, Liu Z. (2013) Curcumin down-regulates DNA methyltransferase 1 and plays an anti-leukemic role in acute myeloid leukemia. PLoS One 8: e55934.
4. Wang QE*, Han C, Zhao R, Wani G, Zhu Q, Gong L, Battu A, Racoma I, Sharma N, Wani AA*. (2013) p38 MAPK- and Akt-mediated p300 phosphorylation regulates its degradation to facilitate nucleotide excision repair. Nucleic Acids Res, 41: 1722-1733 (*: Correspondence author).
5. Wang QE*, Han C, Zhang B, Sabapathy K, Wani AA*. (2012) Nucleotide excision repair factor XPC enhances DNA damage-induced apoptosis by downregulating the anti-apoptotic short isoform of caspase-2. Cancer Res., 72: 666-675 (*: Correspondence author).
6. Wang QE*, Han C, Milum K, Wani AA*. (2011) Stem cell protein Piwil2 modulates chromatin modifications upon cisplatin treatment. Mutats Res, 708: 59-68 (*: Correspondence author)
7. Wang QE*, Milum K, Han C, Huang YW, Wani G, Thomale J, Wani AA*. (2011) Differential contributory roles of nucleotide excision and homologous recombination repair for enhancing cisplatin sensitivity in human ovarian cancer cells. Mol Cancer, 10: 24 (*: Correspondence author)
8. Barakat BM#, Wang QE#*, Han C, Milum K, Zhao Q, Yin DT, Wani G, Arafa ESA, El-Mahdy MA, Wani AA*. (2010) Overexpression of DDB2 enhances the sensitivity of human ovarian cancer cell line to cisplatin by augmenting cellular apoptosis. Int J Cancer, 127: 977-988 (*: Correspondence author; #: Contribute equally)
9. Kanagasabai R, Karthikeyan K, Vedam K, Wang Qien, Zhu Q, and Ilangovan G. (2010) Hsp27 Protects Adenocarcinoma Cells from UV-Induced Apoptosis by Akt and p21-Dependent Pathways of Survival. Mol Cancer Res, 8: 1399-412
10. Ray A, Mir SN, Wani G, Zhao Q, Battu A, Zhu Q, Wang QE, Wani AA (2009). Human SNF5/INI1, a component of the human SWI/SNF chromatin remodeling complex, promotes nucleotide excision repair by influencing ATM recruitment and downstream H2AX phosphorylation. Mol Cell Biol, 29: 6206-19.
11. Zhao Q, Wang QE*, Ray A, Han C, Wani G, Wani AA* (2009). The mammalian SWI/SNF chromatin-remodeling factor is required for efficient nucleotide excision repair in response to UV irradiation. J Biol Chem, 284: 30424-32 (*: Correspondence author)
12. Qin S, Wang Q, Ray A, Wani G, Zhao Q, Bhaumik SR, Wani AA (2009). Sem1p and Ubp6p orchestrate telomeric silencing by modulating histone H2B ubiquitination and H3 acetylation. Nucleic Acids Res, 37: 1843-53.
13. Zhao Q, Barakat BM, Qin S, Ray A, El-Mahdy MA, Wani G, Wang QE*, and Wani AA* (2008). The p38 mitogen-activated protein kinase augments nucleotide excision repair by mediating DDB2 degradation and chromatin relaxation. J Biol Chem, 283: 32553-61. (*: Correspondence author)
14. El-Mahdy MA, Zhu Q, Wang QE, Wani G, Patnaik S, Zhao Q, Arafa ES, Barakat B, Mir SN, Wani AA (2008). Naringenin Protects HaCaT Human Keratinocytes Against UVB-induced Apoptosis and Enhances the Removal of Cyclobutane Pyrimidine Dimers from the Genome. Photochem Photobiol, 84: 307-316.
15. Wang QE*, Prætorius-Ibba M, Zhu Q, El-Mahdy MA, Wani G, Zhao Q, Qin S, Patnaik S, and Wani AA* (2007). UV-induced ubiquitylation-independent Xeroderma pigmentosum group C protein degradation is required for efficient nucleotide excision repair. Nucleic Acids Res, 35: 5338-5380. (*: Correspondence author)
16. Zhu Q, Wani G, Yao J, Patnaik S, Wang QE, El-Mahdy MA, Prætorius-Ibba M, and Wani AA (2006). The ubiquitin proteasome system regulates p53-mediated transcription at p21waf1 promoter. Oncogene, 26: 4199-44208.
17. Prætorius-Ibba M, Wang QE, Wani G, El-Mahdy MA, Zhu Q, Qin S, and Wani AA (2006). Role of claspin in regulation of nucleotide excision repair factor DDB2. DNA Repair, 6: 578-587.
18. Li J*, Wang QE*, Zhu Q, El-Mahdy MA, Wani G, Prætorius-Ibba M, and Wani AA (2006). DNA damage binding component DDB1 participates in nucleotide excision repair through DDB2 DNA binding and cullin 4A ubiquitin ligase activity. Cancer Res, 66: 8590-8597. (*: Contributed equally)
19. El-Mahdy MA, Zhu Q, Wang QE, Wani G, Praetorius-Ibba M, and Wani AA (2006). Cullin 4A-mediated proteolysis of DDB2 protein at DNA damage sites regulates in vivo lesion recognition by XPC. J Biol Chem, 281: 13404-13411
20. Wang QE, Zhu Q, Wani G, El-Mahdy MA, Li J and Wani AA (2005). DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation. Nucleic Acid Res, 33: 4023-4034
21. Zhu Q, Wani G, Wang QE, El-Mahdy M, Snapka RM, Wani AA (2005). Deubiquitination by proteasome is coordinated with substrate translocation for proteolysis in vivo. Exp Cell Res, 307: 436-51
22. El-Mahdy MA, Zhu Q, Wang QE, Wani G, Wani AA (2005). Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells. Int J Cancer, 117: 409-417
23. Wang QE, Wani MA, Chen J, Zhu Q, Wani G, El-Mahdy MA, and Wani AA (2005). Cellular ubiquitination and proteasomal functions positively modulate mammalian nucleotide excision repair. Mol Carcinog, 42: 53-64
24. Wang QE, Zhu Q, Wani G, Cheng J, Wani AA (2004). UV radiation-induced XPC translocation within chromatin is mediated by damaged-DNA binding protein, DDB2. Carcinogenesis, 25: 1033-1043
25. Zhu Q, Yao J, Wani G, Chen J, Wang QE, Wani AA (2004). The ubiquitin-proteasome pathway is required for the function of the viral VP16 transcriptional activation domain. FEBS Lett, 556: 19-25
26. Wang Q, Zhu Q, Wani MA, Wani G, Chen J, Wani AA (2003). Tumor suppressor p53 dependent recruitment of nucleotide excision repair factors XPC and TFIIH to DNA damage. DNA Repair, 2: 483-499
27. Wani MA, El-Mahdy MA, Hamada FM, Wani G, Zhu Q, Wang QE, Wani AA (2002). Efficient repair of bulky anti-BPDE DNA adducts from non-transcribed DNA strand requires functional p53 but not p21(waf1/cip1) and pRb. Mutat Res, 505: 13-25
28. Fan JG, Wang QE, and Liu SJ (2001). Ameliorated chrysotile-induced DNA damage in human embryo lung cells by surface modification of chrysotile with rare earth compounds. Biomed Environ Sci, 14: 220-228
29. Wang Q, Fan J, Wang H, and Liu S (2000). DNA damage and activation of c-ras in human embryo lung cells exposed to chrysotile and cigarette smoking solution. J Environ Pathol Toxicol Oncol, 19: 13-19
30. Fan JG, Wang QE, and Liu SJ (2000). Chrysotile-induced cell transformation and transcriptional changes of c-myc oncogene in human embryo lung cells. Biomed Environ Sci, 13: 163-169
31. Wang QE, Han CH, Wu WD, Wang HB, Liu SJ, and Kohyama N (1999). Biological effects of man-made mineral fibers (I) — Reactive oxygen species production and calcium homeostasis in alveolar macrophages. Ind Health, 37: 62-67
32. Wang QE, Han CH, Yang YP, Wang HB, Wu WD, Liu SJ, and Kohyama N (1999). Biological effects of man-made mineral fibers (II) — Their genetic damages examined by in vitro assay. Ind Health, 37: 342-347
33. Fan JG, Wang QE, Wu WD, Jia G, Liu SJ, and Zhou LL (1998). Pretreatment of chrysotile with rare earth compounds lowered its cytotoxicity by lessening surface charges. Biomed Environ Sci, 11: 125-132