Research
Our research focuses on the following four areas:
1. AI-driven bioinformatic tool development
Our group has developed several widely used bioinformatics resources, including The Cancer Proteome Atlas (TCPA), The Atlas of Noncoding RNA in Cancer (TANRIC), the Functional Annotation of Somatic Mutations in Cancer (FASMIC) and DrBioRight. TCPA serves as the official site for The Cancer Genome Atlas (TCGA) functional proteomic data, while TANRIC has become a leading tool for studying long noncoding RNAs (lncRNAs) in cancer. DrBioRight, a pioneering natural language processing (NLP)/artificial intelligence (AI) platform for cancer omics data, anticipated the development of large language models like ChatGPT. Collectively, these tools have been utilized by >200,000 researchers from >100 countries, greatly advancing the field of cancer bioinformatics.
2. Characterization of tumor-intrinsic vulnerabilities for precision oncology
Our group has made significant contributions to identifying driver somatic alterations and combination therapies. Our team developed an efficient functional genomics approach that combines high-throughput mutant construction, cell viability assays and drug response assays, resulting in the annotation of the functional effects of >1,000 mutations and 100 gene fusions (). Using reverse-phase protein array (RPPA)-based functional proteomics approaches, our studies have led to the discovery of synthetic lethality pairs and combined therapies targeting adaptive signaling rewiring (; ; ).
3. Characterization of tumor-microenvironment vulnerabilities for cancer immunotherapy
Our group has conducted disease-focused, clinically-oriented studies using single cell and spatially resolved techniques. We uncovered an unexpected role of tumor-intrinsic SIRPA in promoting sensitivity to anti-PD-1/PD-L1 therapy in melanoma (). Our team also characterized the immune microenvironment of gastric signet-ring cell carcinoma, revealing key modulators of immune resistance (). Our recent work on the tumor microenvironment in high-grade serous ovarian cancer under PARP inhibition has paved the way for new clinical trials of combination therapies targeting eTreg cells ().
4. RNA modification in cancer development and therapy
Our group is pioneering the study of A-to-I RNA editing in cancer. Our systematic analyses have characterized the A-to-I RNA editing landscape in human cancers, revealing that RNA editing may introduce as many amino acid changes in cancer cells as somatic mutations (; ; ). These studies have added a new dimension to our understanding of proteomic and genomic diversity in cancer, and this research was named the Signaling Breakthrough of the Year by Science Signaling. Our team has explored therapeutic opportunities related to RNA editing, including edited miR-379-5p as an apoptosis-inducing therapeutic () and ADAR1-deficient macrophages for effective immunotherapy (). These findings have been highlighted in Cancer Discovery, Nature Reviews Cancer, and Trends in Cancer.