Zhigang C. Wang, PhD
Assistant Professor, Department of Surgery, Harvard Medical School
Assistant Professor, Cancer Biology, Dana-Farber Cancer Institute
DF/HCC Program AffiliationBreast Cancer
Dr. Wang’s major research interest is the genomics of breast cancers. The goals of his research are to subclassify invasive breast cancers at genetic levels in combination with gene expression profiling, characterize the disease-associated genetic aberrations, and discover genes critical for the pathogenesis of breast cancers. The major strategy of his research integrates microgenomic/ human single nucleotide polymorphism (SNP) array and gene expression array analysis in human breast tumors, clinical outcome of the patients and functional characterization of the candidate genes in vitro and in vivo. Using microgenomic approach with Human SNP array, he and his colleagues discovered genetic instability and signature chromosomal alterations in a basal-like subset of sporadic breast cancers, similar to BRCA1 germline mutation-associated cancers. The observation provides the rationale for development of a new neo-adjuvant therapy targeting genetic instability for basal-like breast cancers. With high density SNP array analysis for both uniparental chromosomal loss and DNA copy number, he and his colleagues discovered frequent X chromosome isodisomy in sporadic basal-like and BRCA1-associated breast cancers, which indicates the potential role of duplication of active X chromosome in pathogenesis of breast cancers. Recently, he and his colleagues, using integrated genomic approach, discovered that 8q22 amplification is associated with early distant recurrence of breast cancers in patients received post-surgery chemotherapy. Using siRNA and gene transfection, they found the contribution of the novel cancer gene LAPTM4B and its neighbor gene YWHAZ on 8q22 to breast cancer resistance to the commonly used chemotherapeutic drug anthracyclines by induction of lysosomal distribution of drugs in tumor cells and inhibition of drug-induced cell death. The two genes were further found to be capable of prediction for the treatment resistance to anthracyclines in a clinical trial of breast cancer. He closely collaborates with Dr. Andrea Richardson in Pathology in their research and also with other investigators in two projects of DF/Harvard SPORE in Breast Caner. His major focus in these projects is using Affymetrix high density SNP array and molecular inversion probes (MIP) technologies to identify the patterns of chromosomal alterations and genetic instability associated with biology and treatment of BRCA1-associated and sporadic basal-like breast cancers, and metastasis in breast cancer patients. Recently, he extends his genomic research to ovarian cancer.
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