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Lin Zhang, M.D.

Harry Fields Research Professor
Department: Obstetrics and Gynecology

Contact information
University of Pennsylvania School of Medicine
421 Curie Blvd, Biomedical Research Building II/III
Lab: 1233~1237; Office: 1207
Philadelphia, PA 19104
Office: 215-573-4780
Fax: 215-573-7627
Lab: 215-573-7947
Post-Graduate Training
Postdoctoral Researcher, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, PA , 2000-2003.
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Description of Research Expertise

Our research has been focused on unraveling the molecular mechanisms underlying ovarian and breast cancers and developing innovative immunotherapies and targeted therapies for these diseases. Our early and ongoing research has focused on investigating the antitumor immune response and developing immunotherapy strategies specifically for ovarian cancer. We provided robust clinical evidence supporting the concept of immune surveillance in ovarian cancer (New England Journal of Medicine, 2003). We demonstrated that the tumor microenvironment promotes immune tolerance and angiogenesis through chemokines and regulatory T cells (Nature, 2011). Currently, our research aims to unravel the contribution of recurrent genomic alterations in both protein-coding and non-coding regions to tumorigenesis, with a specific emphasis on identifying therapeutic targets and combination strategies for treating ovarian and breast cancer. To achieve this, we have developed a novel computational approach that integrates large-scale genomic, functionomic, and pharmcologomic profiles. Our efforts have resulted in the creation of the Functional Cancer Genome data portal (FCG, http://fcgportal.org/home/), to functionally annotate cancer genomes (Cancer Cell, 2014, 2015, 2018; Nature Structural and Molecular Biology, 2016; Nature Cancer, 2021). Our research has revealed that genes encoding histone modification enzymes exhibit high-frequency recurrent genomic alterations in cancers, highlighting their potential as clinically actionable drug targets (Nature Communications, 2019; Cell Reports, 2020, 2022). Most recently, we have demonstrated the efficacy and tolerability of a combination treatment strategy known as "treatment-induced BRCAness" in both primary and acquired HR-proficient tumors (Science Translational Medicine, 2017). This innovative combination approach is currently undergoing evaluation in a phase 2 clinical trial and has shown promising treatment responses.

Noncoding RNAs in epigenetic regulation and DNA damage response.
We were one of the first laboratories to comprehensively characterize long noncoding RNA dysregulation in a large sample cohort. Through our multidimensional genomic analysis, we have made notable discoveries linking long noncoding RNA alterations to somatic copy number changes, promoter hypermethylation, and cancer risk-associated single nucleotide polymorphisms (SNPs). Using a genomic-guided genetic screening approach, our laboratory has identified several cancer-associated noncoding RNAs and extensively investigated their functions in epigenetic regulation and the DNA damage response.

Immunotherapy and targeted therapy for ovarian and breast cancer treatment.
Our early and ongoing research is dedicated to characterizing the antitumor immune response and developing innovative immunotherapy and targeted therapy strategies for cancer patients. Recently, utilizing a computational biology approach, our laboratory has conducted functional characterization of genomic alterations in druggable genes, including epigenetic regulatory genes, across various cancer types. This comprehensive analysis has led to the identification of novel therapeutic targets and the formulation of effective drug combination strategies. Notably, we have provided robust rationale for the "treatment-induced BRCAness" strategy in the treatment of both intrinsic and acquired HR-proficient cancers.

Functional characterization of the cancer genomes.
By employing a combination of multiple computational algorithms, our laboratory has developed a systems biology approach to integrate multi-dimensional and large-scale genomic profiles. This innovative approach has led to the creation of a publicly accessible database known as the Functional Cancer Genome data portal (FCG data portal). With the aim of aiding researchers in the analysis and visualization of cancer genomic data, we have released multiple genomic data sets through our FCG data portal, including the Cancer LncRNome Atlas (TCLA) and the Cancer Genetic Ancestry Atlas (TCGAA). These resources provide valuable tools for the scientific community to explore and unravel the complexities of cancer genomics.

Selected Publications

Zhang L, Conejo-Garcia JR, Katsaros D, Gimotty PA, Massobrio M, Regnani G, Makrigiannakis A, Gray H, Schlienger K, Liebman M N, Rubin SC, Coukos G: Intratumoral T cells, recurrence, and survival in epithelial ovarian cancer. New England Journal of Medicine 348(3): 203-13, Jan 2003.

Hu X, Feng Y, Zhang D, Zhao SD, Hu Z, Greshock J, Zhang Y, Yang L, Zhong X, Wang L-P, Jean S, Li C, Huang Q, Katsaros D, Montone KT, Tanyi JL, Lu Y, Boyd J, Nathanson KL, Li H, Mills GB, Zhang L: A Functional Genomic Approach Identifies FAL1 as an Oncogenic Long Noncoding RNA that Associates with BMI1 and Represses p21 Expression in Cancer. Cancer Cell 26(3): 344-57, Sep 2014.

Yan X, Hu Z, Feng Yi, Hu X, Yuan J, Zhao SD, Zhang Y, Yang L, Shan W, He Q, Fan L, Kandalaft LE, Tanyi JL, Li C, Yuan C-X, Zhang D, Yuan H, Hua K, Lu Y, Katsaros D, Huang Q, Montone K, Fan Y, Coukos G, Boyd J, Sood AK, Rebbeck T, Mills GB, Dang CV, Zhang L: Comprehensive Genomic Characterization of Long Non-coding RNAs across Human Cancers. Cancer Cell 28(4): 529-40, Oct 2015.

Zhang Y, He Q, HU Z, Feng Y, Fan L, Tang Z, Yuan J, Shan W, Li C, Hu X, Tanyi JL, Fan Y, Huang Q, Montone K, Dang CV, Zhang L: Long noncoding RNA LINP1 regulates repair of DNA double-strand breaks in triple-negative breast cancer. Nat Struct Mol Biol 23(6):522-30, Apr 2016.

Yang L, Zhang Y, Shan W, Hu Z, Yuan J, Pi J, Wang Y, Fan L, Tang Z, Li C, Hu X, Tanyi JL, Fan Y, Huang Q, Montone K, Dang CV, Zhang L: Repression of BET activity sensitizes homologous recombination-proficient cancers to PARP inhibition. Sci Transl Med 26:9(400), Jul 2017.

Yuan J, Hu Z, Mahal B, Zhao S, Kensler K, Pi J, Hu X, Wang Y, Jiang J, Zhang Y, Li C, Zhong X, Montone K, Guan G, Tanyi J, Fan Y, Xu X, Long M, Morgan M, Zhang Y, Zhang R, Sood A, Rebbeck T, Dang C, Zhang L: Integrated analysis of genetic ancestry and genomic alterations across cancers. Cancer Cell 34(4):549-560.e9, 2018.

Zhongyi Hu, Junzhi Zhou, Junjie Jiang, Jiao Yuan, Youyou Zhang, Xuepeng Wei, Nicki Loo, Yueying Wang, Yutian Pan, Tianli Zhang, Xiaomin Zhong, Meixiao Long, Kathleen Montone, Janos Tanyi, Yi Fan, Tian-Li Wang, Ie-Ming Shih, Xiaowen Hu, Lin Zhang: Genomic characterization of genes encoding histone acetylation modulator proteins identifies therapeutic targets for cancer treatment. Nature Communications Page: Feb 13;10(1):733. doi: 10.1038/s41467-019-08554-x. 2019.

Shan W, Yuan J, Hu J, Jiang J, Wang Y, Loo N, Fan L, Tang Z, Zhang T, Xu M, Pan Y, Lu J, Long M, Tanyi LJ, Montone KT, Fan Y, Hu X, Zhang Y, Zhang L.: Systematic characterization of recurrent genomic alterations in cyclin-dependent kinases reveals potential therapeutic strategies for cancer treatment. Cell Reports 32 (2), 107884, 2020.

Hu Z, Yuan J, Long M, Jiang J, Zhang Y, Zhang T, Xu M, Fan Y, Tanyi JL, Montone KT, Tavana O, Chan HM, Hu X, Vonderheide RH, Zhang L: The Cancer Surfaceome Atlas integrates genomic, functional and drug response data to identify actionable targets. Nat Cancer 2(12):1406-1422, Dec 2021.

Jiang J, Yuan J, Hu Z, Zhang Y, Zhang T, Xu M, Long M, Fan Y, Tanyi JL, Montone KT, Tavana O, Vonderheide RH, Chan HM, Hu X, Zhang L.: Systematic illumination of druggable genes in cancer genomes. Cell Rep 38: 110400, Feb 2022.

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Last updated: 09/14/2023
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