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Wenge Zhu Scientific leader of the GW Cancer Center Molecular Therapeutics Focus Group Professor of Biochemistry and Molecular Medicine Office Phone: 202-994-3125 Email: Email Department: Biochemistry and Molecular Medicine |
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Education
- BS, Nankai University, 1990
- PhD, University of Vermont, 2003
Biography
Dr. Wenge Zhu is a Professor of Biochemistry and Molecular Medicine Department at The George Washington University School of Medicine and Health Science. He was trained in cell and molecular biology at University of Vermont, Harvard Medical School, University of Virginia and NIH before joining GWU as an assistant professor. His group focus on DNA replication, cell cycle, DNA repair, drug discovery and drug resistance in cancer with supporting by multiple grants from NIH and ACS. In addition to basic research, his group has identified multiple compounds for potential cancer treatment and filed five patents for cancer therapy. Currently, he is an associate editor for Cancer Medicine and editorial board member of JBC. He also serves as the permanent or Ad hoc review members for multiple study sections of NIH, ACS, etc.
Research
Research Interests
DNA replication, DNA damage checkpoint and repair, drug resistance, and identification of small molecules for cancer therapy.
Research Program
Maintenance of genome stability is extremely important in the cell cycle because instable genome is the primary contribution to cancer formation. Cells have evolved multiple mechanisms to prevent genomic instability during genome duplication, including DNA damage checkpoint, DNA damage repair, regulation of DNA replication, etc. The objective of our research is to investigate the mechanisms of how our cells maintain the stability of their genome and to utilize this information to identify new drugs for cancer treatment.
To accomplish this goal, we are conducting following research work. (1) Investigate the mechanisms of how cells response to DNA damage and repair damaged DNA. (2) Investigate the mechanisms of anti-cancer drug resistance to improve cancer treatment. (3) Investigate how cells prevent DNA re-replication (one type of genomic stability) in both normal and cancer cells. (4) Identify small molecules through HTS for cancer therapy.
Grants
1. ACS Research Scholar Grant RSG-13-214-01, “The role of And-1 in DNA damage repair”
2. NIH/NCI 1R01CA177898 “ The role of And-1 in DNA damage response”
3. NIH/NCI 1R01CA184717 “The Regulation of Cisplatin Resistance in Ovarian Cancer ”
Awards
2014 Elaine H. Snyder Cancer Research Award
2013 American Cancer Society Scholar
2009 NIH/NCI Pathway to Independence (PI) Award (K99/R00)
2007 NIH/Ruth Kirschstein National Research Service Award (NRSA, F32)
Teaching
1. Molecular Medicine (Bioc 6222)
2. Medical Genomics
3. Faculty Oncology Research Seminar (MMED8222)
4. Student seminar course (Bioc 227)
5. Fundamentals of Molecular Biology (Bioc 6254)
6. The Basic Science of Oncology (MMED 221)
7. Molecular and Cellular Signaling (Bioc 8231)
Centers and Institutes
GWU Cancer Center
Programs
- GW Cancer Center
Publications
Zhang Y, Zhou S, Kai Y, Zhang YQ, Peng C, Li Z, Mughal MJ, Julie B, Zheng X, Ma J, Ma CX, Shen M, Hall MD, Li S, Zhu W. O-GlcNAcylation of MITF regulates its activity and CDK4/6 inhibitor resistance in breast cancer. Nat Commun. 2024 Jul 3;15(1):5597. PubMed PMID: 38961064.
Hou C, Wu C, Zhu W, Pei H, Ma J. Systematic pan-cancer analysis reveals OGT and OGA as potential biomarkers for tumor microenvironment and therapeutic responses. Genes Dis. 2024 Jul;11(4):101089. PubMed PMID: 38362042.
Zhang Y, Li J, Zhou Y, Li Z, Peng C, Pei H, Zhu W. And-1 Coordinates with the FANCM Complex to Regulate Fanconi Anemia Signaling and Cisplatin Resistance. Cancer Res. 2022 Sep 16;82(18):3249-3262. PubMed PMID: 35867033.
Zhou Y, Zhang Y, Peng C, Li Z, Pei H, Pei H, Zhu W. And-1 O-GlcNAcylation regulates homologous recombination repair and radioresistance in colorectal cancer. Clin Transl Med. 2022 Apr;12(4): e785. PubMed PMID: 35474639.
Li J, Zhang Y, Sun J, Chen L, Gou W, Chen CW, Zhou Y, Li Z, Chan DW, Huang R, Pei H, Zheng W, Li Y, Xia M, Zhu W. Discovery and characterization of potent And-1 inhibitors for cancer treatment. Clin Transl Med. 2021 Dec;11(12): e627. PubMed PMID: 34923765.
Zhang Y, Wei H, Zhou Y, Li Z, Gou W, Meng Y, Zheng W, Li J, Li Y, Zhu W. Identification of potent SENP1 inhibitors that inactivate SENP1/JAK2/STAT signaling pathway and overcome platinum drug resistance in ovarian cancer. Clin Transl Med. 2021 Dec;11(12): e649. PubMed PMID: 34954894.
Tan W, Jiang P, Zhang W, Hu Z, Lin S, Chen L, Li Y, Peng C, Li Z, Sun A, Chen Y, Zhu W, Xue Y, Yao Y, Li X, Song Q, He F, Qin W, Pei H. Posttranscriptional regulation of de novo lipogenesis by glucose-induced O-GlcNAcylation. Mol Cell. 2021 May 6;81(9):1890-1904.e7. PubMed PMID: 33657401.
Li J, Wu R, Yung MMH, Sun J, Li Z, Yang H, Zhang Y, Liu SS, Cheung ANY, Ngan HYS, Braisted JC, Zheng W, Wei H, Gao Y, Nemes P, Pei H, Chan DW, Li Y, Zhu W. SENP1-mediated deSUMOylation of JAK2 regulates its kinase activity and platinum drug resistance. Cell Death Dis. 2021 Apr 1;12(4):341. PubMed PMID: 33795649.
Hu Z, Mi S, Zhao T, Peng C, Peng Y, Chen L, Zhu W, Yao Y, Song Q, Li X, Li X, Jia C, Pei H. BGL3 lncRNA mediates retention of the BRCA1/BARD1 complex at DNA damage sites. EMBO J. 2020 Jun 17;39(12):e104133. PubMed PMID: 32347575.
Moufarrij S, Srivastava A, Gomez S, Hadley M, Palmer E, Austin PT, Chisholm S, Diab N, Roche K, Yu A, Li J, Zhu W, Lopez-Acevedo M, Villagra A, Chiappinelli KB. Combining DNMT and HDAC6 inhibitors increases anti-tumor immune signaling and decreases tumor burden in ovarian cancer. Sci Rep. 2020 Feb 26;10(1):3470. PubMed PMID: 32103105.
Zhang Y, Wu X, Kai Y, Lee CH, Cheng F, Li Y, Zhuang Y, Ghaemmaghami J, Chuang KH, Liu Z, Meng Y, Keswani M, Gough NR, Wu X, Zhu W, Tzatsos A, Peng W, Seto E, Sotomayor EM, Zheng X. Secretome profiling identifies neuron-derived neurotrophic factor as a tumor-suppressive factor in lung cancer. JCI Insight. 2019 Dec 19;4(24). PubMed PMID: 31852841.
Li Z, Zhou W, Zhang Y, Sun W, Yung MMH, Sun J, Li J, Chen CW, Li Z, Meng Y, Chai J, Zhou Y, Liu SS, Cheung ANY, Ngan HYS, Chan DW, Zheng W, Zhu W. ERK Regulates HIF1?-Mediated Platinum Resistance by Directly Targeting PHD2 in Ovarian Cancer. Clin Cancer Res. 2019 Oct 1;25(19):5947-5960. PubMed PMID: 31285371.
Zhang Y, Li Z, Hao Q, Tan W, Sun J, Li J, Chen CW, Li Z, Meng Y, Zhou Y, Han Z, Pei H, DePamphilis ML, Zhu W. The Cdk2-c-Myc-miR-571 Axis Regulates DNA Replication and Genomic Stability by Targeting Geminin. Cancer Res. 2019 Oct 1;79(19):4896-4910. PubMed PMID: 31431461.
Dai S, Yang S, Hu X, Sun W, Tawa G, Zhu W, Schimmer AD, He C, Fang B, Zhu H, Zheng W. 17-Hydroxy Wortmannin Restores TRAIL's Response by Ameliorating Increased Beclin 1 Level and Autophagy Function in TRAIL-Resistant Colon Cancer Cells. Mol Cancer Ther. 2019 Jul;18(7):1265-1277. PubMed PMID: 31092562.
Peng Y, Liao Q, Tan W, Peng C, Hu Z, Chen Y, Li Z, Li J, Zhen B, Zhu W, Li X, Yao Y, Song Q, Liu C, Qi X, He F, Pei H. The deubiquitylating enzyme USP15 regulates homologous recombination repair and cancer cell response to PARP inhibitors. Nat Commun. 2019 Mar 15;10(1):1224. PubMed PMID: 30874560.
Chen CW, Li Y, Hu S, Zhou W, Meng Y, Li Z, Zhang Y, Sun J, Bo Z, DePamphilis ML, Yen Y, Han Z, Zhu W. DHS (trans-4,4'-dihydroxystilbene) suppresses DNA replication and tumor growth by inhibiting RRM2 (ribonucleotide reductase regulatory subunit M2). Oncogene. 2019 Mar;38(13):2364-2379. PubMed PMID: 30518875.
Sun J, Cai X, Yung MM, Zhou W, Li J, Zhang Y, Li Z, Liu SS, Cheung ANY, Ngan HYS, Li Y, Dai Z, Kai Y, Tzatsos A, Peng W, Chan DW, Zhu W. miR-137 mediates the functional link between c-Myc and EZH2 that regulates cisplatin resistance in ovarian cancer. Oncogene. 2019 Jan;38(4):564-580. PubMed PMID: 30166592.
Tian T, Wang M, Zhu Y, Zhu W, Yang T, Li H, Lin S, Dai C, Deng Y, Song D, Li N, Zhai Z, Dai ZJ. Expression, Clinical Significance, and Functional Prediction of MNX1 in Breast Cancer. Mol Ther Nucleic Acids. 2018 Dec 7; 13:399-406. PubMed PMID: 30368216.
Tian T, Wang M, Lin S, Guo Y, Dai Z, Liu K, Yang P, Dai C, Zhu Y, Zheng Y, Xu P, Zhu W, Dai Z. The Impact of lncRNA Dysregulation on Clinicopathology and Survival of Breast Cancer: A Systematic Review and Meta-analysis. Mol Ther Nucleic Acids. 2018 Sep 7; 12:359-369. PubMed PMID: 30195774.
Sima N, Sun W, Gorshkov K, Shen M, Huang W, Zhu W, Xie X, Zheng W, Cheng X. Small Molecules Identified from a Quantitative Drug Combinational Screen Resensitize Cisplatin's Response in Drug-Resistant Ovarian Cancer Cells. Transl Oncol. 2018 Aug;11(4):1053-1064. PubMed PMID: 29982103.
Meng Y, Chen CW, Yung MMH, Sun W, Sun J, Li Z, Li J, Li Z, Zhou W, Liu SS, Cheung ANY, Ngan HYS, Braisted JC, Kai Y, Peng W, Tzatsos A, Li Y, Dai Z, Zheng W, Chan DW, Zhu W. DUOXA1-mediated ROS production promotes cisplatin resistance by activating ATR-Chk1 pathway in ovarian cancer. Cancer Lett. 2018 Aug 1; 428:104-116. PubMed PMID: 29704517.
Zhou W, Sun W, Yung MMH, Dai S, Cai Y, Chen CW, Meng Y, Lee JB, Braisted JC, Xu Y, Southall NT, Shinn P, Huang X, Song Z, Chen X, Kai Y, Cai X, Li Z, Hao Q, Cheung ANY, Ngan HYS, Liu SS, Barak S, Hao J, Dai Z, Tzatsos A, Peng W, Pei H, Han Z, Chan DW, Zheng W, Zhu W. Autocrine activation of JAK2 by IL-11 promotes platinum drug resistance. Oncogene. 2018 Jul;37(29):3981-3997. PubMed PMID: 29662190.
Tian T, Wang M, Zheng Y, Yang T, Zhu W, Li H, Lin S, Liu K, Xu P, Deng Y, Zhou L, Dai Z. Association of two FOXP3 polymorphisms with breast cancer susceptibility in Chinese Han women. Cancer Manag Res. 2018; 10:867-872. PubMed PMID: 29731666.
Wang M, Tian T, Ma X, Zhu W, Guo Y, Duan Z, Fan J, Lin S, Liu K, Zheng Y, Sheng Q, Dai ZJ, Peng H. Genetic polymorphisms in caveolin-1 associate with breast cancer risk in Chinese Han population. Oncotarget. 2017 Oct 31;8(53):91654-91661. PubMed PMID: 29207674.
Dai ZJ, Liu XH, Wang M, Guo Y, Zhu W, Li X, Lin S, Tian T, Liu K, Zheng Y, Xu P, Jin T, Li X. IL-18 polymorphisms contribute to hepatitis B virus-related cirrhosis and hepatocellular carcinoma susceptibility in Chinese population: a case-control study. Oncotarget. 2017 Oct 6;8(46):81350-81360. PubMed PMID: 29113394.
Lin S, Wang M, Liu X, Zhu W, Guo Y, Dai Z, Yang P, Tian T, Dai C, Zheng Y, Hu C, Wei L, Dai Z. Association of genetic polymorphisms in MIF with breast cancer risk in Chinese women. Clin Exp Med. 2017 Aug;17(3):395-401. PubMed PMID: 27844180.
Li Y, Li Z, Wu R, Han Z, Zhu W. And-1 is required for homologous recombination repair by regulating DNA end resection. Nucleic Acids Res. 2017 Mar 17;45(5):2531-2545. PubMed PMID: 27940557.
Tian T, Wang M, Zhu W, Dai ZM, Lin S, Yang PT, Liu XH, Liu K, Zhu YY, Zheng Y, Liu M, Dai ZJ. MiR-146a and miR-196a-2 polymorphisms are associated with hepatitis virus-related hepatocellular cancer risk: a meta-analysis. Aging (Albany NY). 2017 Jan 31;9(2):381-392. PubMed PMID: 28148887.
Vassilev A, Lee CY, Vassilev B, Zhu W, Ormanoglu P, Martin SE, DePamphilis ML. Identification of genes that are essential to restrict genome duplication to once per cell division. Oncotarget. 2016 Jun 7;7(23):34956-76. PubMed PMID: 27144335.
Hao J, de Renty C, Li Y, Xiao H, Kemp MG, Han Z, DePamphilis ML, Zhu W. And-1 coordinates with Claspin for efficient Chk1 activation in response to replication stress. EMBO J. 2015 Aug 4;34(15):2096-110. PubMed PMID: 26082189.
Gao L, Li D, Ma K, Zhang W, Xu T, Fu C, Jing C, Jia X, Wu S, Sun X, Dong M, Deng M, Chen Y, Zhu W, Peng J, Wan F, Zhou Y, Zon LI, Pan W. TopBP1 Governs Hematopoietic Stem/Progenitor Cells Survival in Zebrafish Definitive Hematopoiesis. PLoS Genet. 2015 Jul;11(7):e1005346. PubMed PMID: 26131719.
Hao J, Zhu W. Maintain Genomic Stability: Multitask of DNA Replication Proteins. Transcr Open Access. 2015;3(1). PubMed PMID: 29541652.
Jaramillo-Lambert A, Hao J, Xiao H, Li Y, Han Z, Zhu W. Acidic nucleoplasmic DNA-binding protein (And-1) controls chromosome congression by regulating the assembly of centromere protein A (CENP-A) at centromeres. J Biol Chem. 2013 Jan 18;288(3):1480-8. PubMed PMID: 23184928.
Li Y, Xiao H, de Renty C, Jaramillo-Lambert A, Han Z, DePamphilis ML, Brown KJ, Zhu W. The involvement of acidic nucleoplasmic DNA-binding protein (And-1) in the regulation of prereplicative complex (pre-RC) assembly in human cells. J Biol Chem. 2012 Dec 14;287(51):42469-79. PubMed PMID: 23093411.
Lee CY, Johnson RL, Wichterman-Kouznetsova J, Guha R, Ferrer M, Tuzmen P, Martin SE, Zhu W, DePamphilis ML. High-throughput screening for genes that prevent excess DNA replication in human cells and for molecules that inhibit them. Methods. 2012 Jun;57(2):234-48. PubMed PMID: 22503772.
Li Y, Jaramillo-Lambert AN, Yang Y, Williams R, Lee NH, Zhu W. And-1 is required for the stability of histone acetyltransferase Gcn5. Oncogene. 2012 Feb 2;31(5):643-52. PubMed PMID: 21725360.
Li Y, Jaramillo-Lambert A, Hao J, Yang Y, Zhu W. The stability of histone acetyltransferase general control non-derepressible (Gcn) 5 is regulated by Cullin4-RING E3 ubiquitin ligase. J Biol Chem. 2011 Dec 2;286(48):41344-41352. PubMed PMID: 21987584.
Zhu W, Lee CY, Johnson RL, Wichterman J, Huang R, DePamphilis ML. An image-based, high-throughput screening assay for molecules that induce excess DNA replication in human cancer cells. Mol Cancer Res. 2011 Mar;9(3):294-310. PubMed PMID: 21257818.
Zhu W, Depamphilis ML. Selective killing of cancer cells by suppression of geminin activity. Cancer Res. 2009 Jun 1;69(11):4870-7. PubMed PMID: 19487297.
Zhu W, Ukomadu C, Jha S, Senga T, Dhar SK, Wohlschlegel JA, Nutt LK, Kornbluth S, Dutta A. Mcm10 and And-1/CTF4 recruit DNA polymerase alpha to chromatin for initiation of DNA replication. Genes Dev. 2007 Sep 15;21(18):2288-99. PubMed PMID: 17761813.
Zhu W, Dutta A. Activation of fanconi anemia pathway in cells with re-replicated DNA. Cell Cycle. 2006 Oct;5(20):2306-9. PubMed PMID: 17102625.
Zhu W, Dutta A. An ATR- and BRCA1-mediated Fanconi anemia pathway is required for activating the G2/M checkpoint and DNA damage repair upon rereplication. Mol Cell Biol. 2006 Jun;26(12):4601-11. PubMed PMID: 16738325.
Senga T, Sivaprasad U, Zhu W, Park JH, Arias EE, Walter JC, Dutta A. PCNA is a cofactor for Cdt1 degradation by CUL4/DDB1-mediated N-terminal ubiquitination. J Biol Chem. 2006 Mar 10;281(10):6246-52. PubMed PMID: 16407252.
Zhu W, Abbas T, Dutta A. DNA replication and genomic instability. Adv Exp Med Biol. 2005; 570:249-79. PubMed PMID: 18727504.
Zhu W, Chen Y, Dutta A. Rereplication by depletion of geminin is seen regardless of p53 status and activates a G2/M checkpoint. Mol Cell Biol. 2004 Aug;24(16):7140-50. PubMed PMID: 15282313.
Zhu W, Rainville IR, Ding M, Bolus M, Heintz NH, Pederson DS. Evidence that the pre-mRNA splicing factor Clf1p plays a role in DNA replication in Saccharomyces cerevisiae. Genetics. 2002 Apr;160(4):1319-33. PubMed PMID: 11973290.
Zhu W, Li M, Zhao Y. [Analysis of expression of FMR-1 gene in male patients with fragile X syndrome using RT-PCR]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 1998 Feb 10;15(1):17-9. PubMed PMID: 9456366.
Industry Relationships and Collaborations
This faculty member (or a member of their immediate family) has reported a financial interest with the health care related companies listed below. These relations have been reported to the University and, when appropriate, management plans are in place to address potential conflicts.
- None