Mary Zhang (ga5554)

Oncology

• Defining the role of HDAC6 and USP10 in the DNA damage response, DNA repair, and cell death
• Elucidating the role of HDAC6 and USP10 in lung cancer initiation and progression in genetically-engineered mouse models
• Exploring the role of USP10 in anti-tumor immune responses
 

Dr. Zhang’s lab has a long-standing interest in the enzymes responsible for post-translational modifications with a particular interest in histone deacetylases (HDACs) and deubiquitinating enzymes (DUBs). Her lab was the first to show that HDAC6 harbors a novel ubiquitin E3 ligase activity and participates in the DNA damage response and DNA repair. Her lab was among the first to reveal that both HDAC6 and USP10 are associated with cisplatin sensitivity in lung and ovarian cancer. Her lab currently focuses on elucidating the role of HDAC6 and USP10 in lung cancer initiation, progression, the DNA damage response, DNA repair, and cell death using biochemical approaches as well as various cell lines and mouse models.

Allison V Mitchell, Ling Wu, C James Block, Mu Zhang, Justin Hackett, Douglas B Craig, Wei Chen, Yongzhong Zhao, Bin Zhang, Yongjun Dang, Xiaohong Zhang, Shengping Zhang, Chuangui Wang, Heather Gibson, Lori A Pile, Benjamin Kidder, Larry Matherly, Zhe Yang, Yali Dou, Guojun Wu. FOXQ1 recruits the MLL complex to activate transcription of EMT and promote breast cancer metastasis. Nature Communications 2022;13:6548. 

Hu C, Zhang M, Moses N, Hu CL, Polin L, Chen W, Jang H, Heyza J, Malysa A, Caruso JA, Xiang S, Patrick S, Stemmer P, Lou Z, Bai W, Wang C, Bepler G, Zhang XM. The USP10-HDAC6 axis confers cisplatin resistance in non-small cell lung cancer lacking wild-type p53. Cell Death Dis 2020:11:328.

Zhang M, Hu C, Moses N, Haakenson J, Xiang S, Quan D, Fang B, Yang Z, Bai W, Bepler G, Li GM, Zhang, X. HDAC6 regulates DNA damage response via deacetylating MLH1. J Biol Chem. 2019;294:5813-26.

Wu JY, Xiang S, Zhang M, Fang B, Huang H, Kwon OK, Zhao Y, Yang Z, Bai W, Bepler G, Zhang XM. Histone deacetylase 6 (HDAC6) deacetylates extracellular signal-regulated kinase 1 (ERK1) and thereby stimulates ERK1 activity. J Biol Chem. 2018;293:1976-93.

Shan P, Fan G, Sun L, Liu J, Wang W, Hu C, Zhang X, Zhai Q, Song X, Cao L, Cui Y, Zhang S, Wang C. SIRT1 Functions as a Negative Regulator of Eukaryotic Poly(A)RNA Transport. Curr Biol. 2017;27:2271-84.

Niu X, Zhao J, Ma J, Xie C, Edwards H, Wang G, Caldwell JT, Xiang S, Zhang X, Chu R, Wang Z, Lin H, Taub JW, and Ge Y. Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be overcome by combination with daunorubicin or cytarabine in AML cells. Clin Cancer Res 2016;22:4440-51. 

Zhang M, Hu C, Tong D, Xiang S, Williams K, Bai W, Li G-M, Bepler G, Zhang, X. Ubiquitin-Specific Peptidase 10 (USP10) Deubiquitinates and Stabilizes MutS Homolog 2 (MSH2) to Regulate Cellular Sensitivity to DNA Damage. J. Biol. Chem 2016;291:10783-91.

Fan G, Sun L, Shen P, Zhang X, Huan J, Zhang X, Li D, Wang T, Wei T, Zhang X, Gu X, Yao L, Xuan Y, Hou Z, Cui Y, Cao L, Li X, Zhang X, and Wang C. Loss of KLF14 triggers centrosome amplification and tumorigenesis. Nat Commun 2015;6:8450

Radhakrishnan R, Li Y, Xiang S, Yuan F, Yuan Z, Telles E, Fang J, Coppola D, Shibata D, Lane W S, Zhang Y, Zhang X*, and Seto E. Histone Deacetylase 10 Regulates DNA Mismatch Repair and May Involve the Deacetylation of MutS Homolog 2. J. Biol. Chem. 2015;290:22795-804.
 
Zhang M, Xiang S, Joo H-Y, Wang, L, Williams, K, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J., Li C, Gu L, Li G-M, Bai W, Wang H, Zhang X. HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutSα. Mol. Cell 2014:55:31-46.

Ph.D. (1998) U.T. M. D. Anderson Cancer Center, Houston, Texas 

CB7800Rigor and Reproducibility in Cancer Biology (Course Director)
CB7460 Mechanisms of Neoplasia: Alterations to Cellular Signaling-Protein Modification Signaling
CB7300 Biomarkers in Cancer
CB7220 Molecular Biology of Cancer Development
 

Associate Professor
Basic Science

Education
(1993-1998)  Ph.D. Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX
(1991-1993)  M.S. Biochemistry, University of Texas M.D. Anderson Cancer Center, Houston, TX
(1985-1989)  B.S. Biology, Beijing Normal University, Beijing, China

Postgraduate Training
(1998-2006)  Post-Doctoral Fellow, H. Lee Moffitt Cancer Center, University of South Florida College of Medicine, Tampa, FL

Faculty Appointments
(2015-Present)  Associate Professor (Research), Department of Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI
(2012-2015)  Associate Professor (tenured), Department of Pathology & Cell Biology, H. Lee Moffitt Cancer Institute, University of South Florida College of Medicine, Tampa, FL
(2006-2012)  Assistant Professor (tenure track), Department of Pathology & Cell Biology, H. Lee Moffitt Cancer Institute, University of South Florida College of Medicine, Tampa, FL

Hopsital and Other Professional Appointments
(2015-Present)  Member, Karmanos Cancer Institute
(2006-2015)  Member, H. Lee Moffitt Cancer Institute

(2014)  Faculty Outstanding Research Achievement Award, University of South Florida
(2011-2014)  Liz Tilberis Scholar
(2009-2011)  K30 Program Scholar
(2008-2010)  Dean's Academic Performance Award, Morsani College of Medicine
(2007)  Marsha Rivkin Scholar

CB 7300 F31- Special Topics in Cancer Biology - Grant Writing
CB 7460: Mechanisms of Neoplasia - Alteration to Cellular Signaling 
CB 7600: Applied Cancer Biostatistics
CB 7700: Recent Developments in Cancer Biology

Dr. Zhang’s lab has a long-standing interest in the role of histone deacetylases (HDACs) in lung cancer and chemoresistance. Her lab was among the first to reveal that HDAC6 is associated with cisplatin sensitivity in lung and ovarian cancer cell lines. Her team has also identified the extracellular signal-regulated kinase 1/2 (ERK1/2) as a modulator for HDAC6’s enzymatic activity. Most significantly, her group discovered a novel ubiquitin E3 ligase activity within HDAC6 and linked HDAC6 to DNA mismatch repair and DNA damage response. Currently, there are three ongoing projects in her lab: 1) To explore the mechanisms by which HDAC6 regulates lung cancer sensitivity to tyrosine kinase inhibitors (TKIs); 2) To elucidate how ubiquitin-specific peptidase 10 (USP10) governs cisplatin sensitivity via HDAC6; 3) To explore how HDAC6 regulates ERK1 function via deacetylation.

1. Niu X, Zhao J, Ma J, Xie C, Edwards H, Wang G, Caldwell JT, Xiang S, Zhang X, Chu R, Wang Z, Lin H, Taub JW, and Ge Y (2016) Binding of released Bim to Mcl-1 is a mechanism of intrinsic resistance to ABT-199 which can be overcome by combination with daunorubicin or cytarabine in AML cells. Clin Cancer Res (accepted)
2. Zhang M, Hu C, Tong D, Xiang S, Williams K, Bai W, Li G-M, Bepler G, Zhang, X. Ubiquitin-Specific Peptidase 10 (USP10) Deubiquitinates and Stabilizes MutS Homolog 2 (MSH2) to Regulate Cellular Sensitivity to DNA Damage. J. Biol. Chem (in press)
3. Radhakrishnan R, Li Y, Xiang S, Yuan F, Yuan Z, Telles E, Fang J, Coppola D, Shibata D, Lane WS., Zhang Y, Zhang X (co-corresponding author), and Seto E. (2015) Histone Deacetylase 10 Regulates DNA Mismatch Repair and May Involve the Deacetylation of MutS Homolog 2. J. Biol. Chem [Epub ahead of print]; PMID:26221039
4. Sun Y, Sun J, Lungchukiet P, Quarni W, Yang S, Zhang X, Bai W. (2015) Fe65 Suppresses Breast Cancer Cell Migration and Invasion through Tip60 Mediated Cortactin Acetylation. Sci Rep. 13;5:11529. doi: 10.1038/srep11529; PMID: 26166158
5. Kasiappan R, Sun Y, Lungchukiet P, Quarni W, Zhang X, Bai W. (2014) Vitamin D suppresses leptin stimulation of cancer growth through MicroRNA. Cancer Res. 74(21):6194-204; PMID: 25252917
6. Zhang M, Xiang S, Joo H-Y, Wang, L, Williams, K, Liu W, Hu C, Tong D, Haakenson J, Wang C, Zhang S, Pavlovicz RE, Jones A, Schmidt KH, Tang J, Dong H, Shan B, Fang B, Radhakrishnan R, Glazer PM, Matthias P, Koomen J, Seto E, Bepler G, Nicosia SV, Chen J., Li C, Gu L, Li G-M, Bai W, Wang H, Zhang X. (2014) HDAC6 deacetylates and ubiquitinates MSH2 to maintain proper levels of MutS. Mol. Cell 55(1):31-46; PMID:24882211
7. Sun Y, Kasiappan R, Tan J, Webb PL, Quarni W, Zhang X, Bai W. (2014) A novel function of the Fe65 neuronal adaptor in estrogen receptor action in breast cancer cells J. Biol. Chem 289(18):12217-31; PMID:24619425
8. Williams KA, Zhang M, Xiang S, Hu C, Wu JY, Zhang S, Ryan M, Cox AD, Der CJ, Fang B, Koomen J, Haura E, Bepler G, Nicosia SV, Matthias P, Wang C, Bai W, Zhang X (2013) Extracellular Signal-Regulated Kinase (ERK) phosphorylates histone deacetylase 6 (HDAC6) at Serine 1035 to stimulate cell migration. J. Biol. Chem 15;288(46):33156-70; PMID:24089523
9. Wang L, Xiang S, Williams KA, Dong H, Bai W, Nicosia, SV, Khochbin S, Bepler G, Zhang X. (2012) Depletion of HDAC6 enhances cisplatin-induced DNA damage and apoptosis in non-small cell lung cancer cells PLoS ONE 7(9):e44265. Epub 2012 Sep 5
10. Kasiappan R, Sheng Z, Tse AKA, Jinwal U, Tang J, Lungchukiet P, Sun Y, Kruk P, Nicosia SV, Zhang X, Bai W (2012) 1,25-Dihydroxyvitamin D3 suppresses telomerase expression and human cancer growth through microRNA-498. J. Biol. Chem 287(49):41297-309

www.ncbi.nlm.nih.gov/sites/myncbi/xiaohong.zhang.1/bibliography/43444405/public/