Zhigang C. Wang, PhD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 582-7353
Fax: (617) 632-3709


zhigang_wang@dfci.harvard.edu

Zhigang C. Wang, PhD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Assistant Professor, Surgery, Harvard Medical School
  • Assistant Professor, Cancer Biology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Dr. Wang’s major research interest is the functional genomics of breast and ovarian cancers and focuses on genomic sub-classification and novel target discovery in the two diseases. The major strategy of his research integrates the microgenomic/ human single nucleotide polymorphism (SNP) array, gene expression and exome-sequencing data in tumors and clinical outcome of the patients. He collaborated with the pathologists and GYN oncologists at the Brigham and Women’s Hospital and Dana-Farber to acquire SNP array datasets from four cohorts of breast and ovarian cancer. He with his colleagues profiled genome-wide chromosomal aberrations, particularly loss of heterozygosity (LOH), in tumors, identified the feature LOH profiles in triple-negative breast cancer, and sub-classfied ovarian cancer into three sub-groups with different treatment outcome. They developed a new approach to quantify allelic imbalance and LOH events in the tumor genome to predict response to chemotherapy in breast and ovarian cancer. He led a study using genome exome sequencing data and discovered the genome-wide burden of somatic mutation in ovarian cancer serves as a novel predictor for clinical treatment outcome in ovarian cancer with BRCA1/2 mutations. He plans to use these genomic approaches to study response to PARP inhibitors in two clinical trials. In another research field, he and his team completed an integrated genomic study and identified the important role of 8q22 amplification and the novel cancer genes LAPTM4B and YWHAZ in metastasis and chemotherapy resistance in breast cancer. The changes in intracellular drug distribution and autophagy activity were discovered as two mechanisms. He conducted a preclinical study whose objective is to overcome chemo-resistance utilizing a lysosomal tropic drug. The work opens a new avenue in the field of drug resistance in cancer and can be translated into clinical practice in the future. Using the same integrated genomic approach, he extends his study to investigate chromosomal alteration and genes associated with chemotherapy resistance in ovarian cancer. Recently he also serves as the head of the breast cancer tissue bank.

 

Publications

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  • Marquard AM, Eklund AC, Joshi T, Krzystanek M, Favero F, Wang ZC, Richardson AL, Silver DP, Szallasi Z, Birkbak NJ. Pan-cancer analysis of genomic scar signatures associated with homologous recombination deficiency suggests novel indications for existing cancer drugs. Biomark Res 2015; 3:9. PubMed
  • Birkbak NJ, Kochupurakkal B, Izarzugaza JM, Eklund AC, Li Y, Liu J, Szallasi Z, Matulonis UA, Richardson AL, Iglehart JD, Wang ZC. Tumor mutation burden forecasts outcome in ovarian cancer with BRCA1 or BRCA2 mutations. PLoS ONE 2013; 8:e80023. PubMed
  • Wang ZC, Birkbak NJ, Culhane AC, Drapkin R, Fatima A, Tian R, Schwede M, Alsop K, Daniels KE, Piao H, Liu J, Etemadmoghadam D, Miron A, Salvesen HB, Mitchell G, Defazio A, Quackenbush J, Berkowitz RS, Iglehart JD, Bowtell DD, , Matulonis UA. Profiles of Genomic Instability in High-Grade Serous Ovarian Cancer Predict Treatment Outcome. Clin Cancer Res 2012; 18:5806-5815. PubMed
  • Utermark T, Rao T, Cheng H, Wang Q, Lee SH, Wang ZC, Iglehart JD, Roberts TM, Muller WJ, Zhao JJ. The p110留 and p110硫 isoforms of PI3K play divergent roles in mammary gland development and tumorigenesis. Genes Dev 2012; 26:1573-86. PubMed
  • Kojima Y, Acar A, Eaton EN, Mellody KT, Scheel C, Ben-Porath I, Onder TT, Wang ZC, Richardson AL, Weinberg RA, Orimo A. Autocrine TGF-{beta} and stromal cell-derived factor-1 (SDF-1) signaling drives the evolution of tumor-promoting mammary stromal myofibroblasts. Proc Natl Acad Sci U S A 2010; 107:20009-14. PubMed
  • Tung N, Miron A, Schnitt SJ, Gautam S, Fetten K, Kaplan J, Yassin Y, Buraimoh A, Kim JY, Szasz AM, Tian R, Wang ZC, Collins LC, Brock J, Krag K, Legare RD, Sgroi D, Ryan PD, Silver D, Garber JE, Richardson AL. Prevalence and predictors of loss of wild type BRCA1 in estrogen receptor positive and negative BRCA1-associated breast cancers. Breast Cancer Res 2010; 12:R95. PubMed
  • Silver DP, Richardson AL, Eklund AC, Wang ZC, Szallasi Z, Li Q, Juul N, Leong CO, Calogrias D, Buraimoh A, Fatima A, Gelman RS, Ryan PD, Tung NM, De Nicolo A, Ganesan S, Miron A, Colin C, Sgroi DC, Ellisen LW, Winer EP, Garber JE. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 2010; 28:1145-53. PubMed
  • Li Y, Zou L, Li Q, Haibe-Kains B, Tian R, Li Y, Desmedt C, Sotiriou C, Szallasi Z, Iglehart JD, Richardson AL, Wang ZC. Amplification of LAPTM4B and YWHAZ contributes to chemotherapy resistance and recurrence of breast cancer. Nat Med 2010; 16:214-8. PubMed
  • Gewinner C, Wang ZC, Richardson A, Teruya-Feldstein J, Etemadmoghadam D, Bowtell D, Barretina J, Lin WM, Rameh L, Salmena L, Pandolfi PP, Cantley LC. Evidence that inositol polyphosphate 4-phosphatase type II is a tumor suppressor that inhibits PI3K signaling. Cancer Cell 2009; 16:115-25. PubMed
  • Valastyan S, Reinhardt F, Benaich N, Calogrias D, Szász AM, Wang ZC, Brock JE, Richardson AL, Weinberg RA. A pleiotropically acting microRNA, miR-31, inhibits breast cancer metastasis. Cell 2009; 137:1032-46. PubMed
  • Wang Y,Carlton VE,Karlin-Neumann G,Sapolsky R,Zhang L,Moorhead M,Wang ZC,Richardson AL,Warren R,Walther A,Bondy M,Sahin A,Krahe R,Tuna M,Thompson PA,Spellman PT,Gray JW,Mills GB,Faham M. High quality copy number and genotype data from FFPE samples using Molecular Inversion Probe (MIP) microarrays. BMC Med Genomics 2009; 2:8. PubMed
  • Cheng H, Liu P, Wang ZC, Zou L, Santiago S, Garbitt V, Gjoerup OV, Iglehart JD, Miron A, Richardson AL, Hahn WC, Zhao JJ. SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis. Sci Signal 2009; 2:ra35. PubMed
  • Lu X, Lu X, Wang ZC, Iglehart JD, Zhang X, Richardson AL. Predicting features of breast cancer with gene expression patterns. Breast Cancer Res Treat 2008; 108:191-201. PubMed
  • Harezlak J,Wu MC,Wang M,Schwartzman A,Christiani DC,Lin X. Biomarker discovery for arsenic exposure using functional data. Analysis and feature learning of mass spectrometry proteomic data. J Proteome Res 2008; 7:217-24. PubMed
  • Wang ZC, Buraimoh A, Iglehart JD, Richardson AL. Genome-Wide Analysis for Loss of Heterozygosity in Primary and Recurrent Phyllodes Tumor and Fibroadenoma of Breast using Single Nucleotide Polymorphism Arrays. Breast Cancer Res Treat 2006; 97:301-9. PubMed
  • Richardson AL, Wang ZC, De Nicolo A, Lu X, Brown M, Miron A, Liao X, Iglehart JD, Livingston DM, Ganesan S. X chromosomal abnormalities in basal-like human breast cancer. Cancer Cell 2006; 9:121-32. PubMed
  • Bentires-Alj M, Gil SG, Chan R, Wang ZC, Wang Y, Imanaka N, Harris LN, Richardson A, Neel BG, Gu H. A role for the scaffolding adapter GAB2 in breast cancer. Nat Med 2005; 12:114-21. PubMed
  • Wang ZC, Lin M, Wei LJ, Li C, Miron A, Lodeiro G, Harris L, Ramaswamy S, Tanenbaum DM, Meyerson M, Iglehart JD, Richardson A. Loss of heterozygosity and its correlation with expression profiles in subclasses of invasive breast cancers. Cancer Res 2004; 64:64-71. PubMed
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