Research

Hypoxia is associated with resistance towards radiation and chemotherapy. As tumors grow, they can sense the oxygen tension and reprogram critical pathways that are important for cancer cell survival and therapy resistance. One of examples is through upregulation of hypoxia inducible factor a (HIFa) and activation of HIF signaling downstream pathways. We are interested in studying the oxygen-sensing pathway and how they contribute to the development of tumors as well as therapeutic resistance. One of the central players in this pathway is prolyl hydroxylase (EglN1, 2 and 3), a family of iron- and 2-oxoglutarate-depedent dioxygenases. EglNs can hydroxylate HIFa on critical proline residues, which will trigger von Hippel-Lindau (VHL)-associated E3 ligase complex binding and lead to HIFa degradation. Our lab currently studies hypoxia, prolyl hydroxylase, and VHL signaling in cancer, especially breast and renal cell carcinomas.

Our Mission

We are at the forefront of discovering novel mechanisms driving cancer development and progression. Our lab combines cutting-edge technologies with innovative thinking to tackle some of the most challenging questions in cancer biology. We're particularly focused on understanding and targeting aggressive cancers like triple-negative breast cancer and kidney cancer, where new therapeutic approaches are urgently needed.

Research Themes and Achievements

1. Novel Cancer Mechanisms and Therapeutic Targets

Clear Cell Renal Cell Carcinoma (ccRCC)

  • VHL-Regulated Pathways: Discovered novel mechanisms controlling gene expression and tumor progression 

    • Identified VHL's role in m6A-dependent gene expression (J Clin Invest, 2024)

    • Characterized JMJD6-DGAT1 signaling in lipid metabolism (Mol Cell, 2022)

    • Uncovered ZHX2 as a critical oncogenic driver (Science, 2018)

  • Therapeutic Vulnerabilities: Identified novel therapeutic targets 

    • Found DCLK2-TBK1 as an oncogenic signaling axis (Mol Cell, 2024)

    • Discovered TBK1 as a synthetic lethal target (Cancer Discovery, 2020)

    • Identified SFMBT1 as a new oncogenic driver (Mol Cell, 2020)

Triple Negative Breast Cancer (TNBC)

  • Metabolic Regulation: Uncovered critical metabolic dependencies 

    • Identified BBOX1 as a therapeutic target (Cancer Discovery, 2020)

    • Developed integrated metabolic profiling approaches (Cancer Research, 2021)

    • Characterized ZHX2-HIF1 oncogenic signaling (eLife, 2021)

2. Protein Modifications in Cancer

Protein Hydroxylation

  • EglN2 Pathway: Pioneered understanding of prolyl hydroxylation in cancer 

    • Discovered EglN2's role in cyclin D1 regulation (Cancer Cell, 2009)

    • Identified FOXO3a regulation mechanism (Genes & Development, 2014)

    • Uncovered EglN2's control of mitochondrial function (EMBO J, 2015)

Deubiquitination Mechanisms

  • Novel Regulatory Pathways: Identified key protein stability controls 

    • Characterized USP13-ZHX2 axis (PNAS, 2022)

    • Discovered USP37-HIF2α regulation (PNAS, 2020)

3. Epigenetic Regulation and Gene Expression

  • Chromatin Modifications: Made groundbreaking discoveries in histone regulation 

    • Identified novel histone H3 proline 16 hydroxylation (Nature Genetics, 2022)

    • Uncovered chromatin oxygen sensing mechanisms

    • Integrated epigenetic and metabolic regulation

Research Environment

Our dynamic research team is dedicated to:

  • Making groundbreaking discoveries in cancer biology

  • Training the next generation of cancer scientists

  • Fostering a collaborative and supportive learning environment

  • Translating scientific findings into therapeutic opportunities