Description of Research Expertise

Our research efforts have been focused on the characterization of molecular mechanisms and the development of novel therapies for cancer by a combination of computational and molecular biology approaches. We reported that long non-coding RNAs exhibit genomic alterations with high frequency in cancer (Cancer Cell 2014, and Cancer Cell 2015). We developed novel strategies to target DNA repair pathways in combination with inhibition of certain long non-coding RNA or epigenetic regulators to treat breast and ovarian cancer (Nature Structural and Molecular Biology 2016, Science Translational Medicine 2017, and Cell Reports 2020). Recently, by integrating large-scale and multi-dimensional genomic profiles, we developed a Functional Cancer Genome data portal (FCG data portal: http://52.25.87.215/home/) to functionally annotate TCGA genomic profiles. Examples include annotations on the relationship between genetic ancestry and genomic alteration (Cancer Cell 2018) and genomic alterations in epigenetic regulatory genes (Nature Communications 2019, and Cell Reports 2022). Our early and still ongoing research is directed towards investigating the antitumor immune response and developing immunotherapy strategies for ovarian cancer. Our studies provided strong clinical evidence to support the concept of immune surveillance in ovarian cancer (New England Journal of Medicine 2003, and Nature Cancer 2021).

1. Noncoding RNAs in epigenetic regulation and DNA damage response.
We comprehensively characterized long noncoding RNA dysregulation in a large sample cohort. Our multidimensional genomic analysis revealed that long noncoding RNA alterations are associated with somatic copy number changes, promoter hypermethylation, and cancer risk-associated 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.

2. Functional characterization of the cancer genomes.
Through a combination of multiple computational algorithms, we developed a systems biology approach to integrate multi-dimensional and large-scale genomic profiles. A publicly accessible database, the Functional Cancer Genome data portal (FCG data portal), has been developed by our laboratory. To assist researchers with analyzing and visualizing TCGA genomic data, multiple genomic data sets have been released via our FCG data portal (FCG data portal: http://52.25.87.215/home/), including the Cancer LncRNome Atlas (TCLA), and the Cancer Genetic Ancestry Atlas (TCGAA).

3. Immunotherapy and targeted therapy for women’s cancer.
Our early and still ongoing research focuses on characterizing the antitumor immune response and on developing new immunotherapy strategies for patients with ovarian cancer. We investigated the correlation between T lymphocyte infiltration and patient survival, providing strong evidence to support the concept of immune surveillance. Recently, using a computational biology approach, our laboratory functionally characterized genomic alterations of the druggable genes, such as epigenetic regulatory genes, across multiple cancer types. We identified novel therapeutic targets and drug combination strategies. For example, we provided rationale for the clinical application of BET inhibitor in combination with PARP inhibitor for cancer treatment.

4. Genomic alterations of microRNA genes in cancer.
We provided experimental documentation of genome-wide microRNA copy number alterations in cancer. Our laboratory has extensively investigated microRNA-based diagnosis and treatment strategies for patients with cancer. We reported that microRNA expression signatures are informative for cancer diagnosis, prognosis, classification, and clinical prediction, and that selected microRNAs can serve as therapeutic targets for cancer treatment.

5. The heterochronic pathway in embryonic stem cell differentiation and cancer development.
We showed strong connections between the heterochronic pathway and tumorigenesis in ovarian and breast cancers. Heterochrony describes the phylogenetic variation in the relative timing of major developmental events between related species. Our laboratory reported that LIN28 promotes tumorigenesis by regulating differentiation and controlling the cell cycle. A nanoparticle-based let-7 replacement therapy has recently been developed in our laboratory.