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.