Assistant Professor, Department of Molecular Medicine, School of Medicine
Member, Immune Oncology Program, Case Comprehensive Cancer Center
Research Information
Research Interests
My research focuses on dissecting the cellular and molecular mechanisms driving cancer development, inflammation, and tumor progression to identify novel therapeutic targets and strategies. A central theme of my work is understanding how Transforming Growth Factor-β (TGF-β) signaling and mechanosensitive pathways regulate immune cell fate, malignant transformation, and metastasis.
Research Projects
1. T-Cell Signaling, Intestinal Inflammation, and Colitis-Associated Cancer (CAC)
- We discovered that small-molecule triterpenoids (e.g., dietary celastrol) suppress CAC development by disrupting T-cell TGF-β signaling, identifying 15-PGDH as a key molecular target. We also demonstrated that loss accelerates CAC via memory T-cell expansion.
- Recently, we uncovered that the mechanosensitive ion channel Piezo1 in T cells is essential for antitumor immunity and the maintenance of effector memory T cells (). While Piezo1 deficiency heightens in vitro cytokine production, it impairs in vivo pathogenicity in inflammatory bowel disease (IBD).
- We will define how Piezo1 integrates mechanical and cytokine signals to control T-cell pathogenicity, aiming to design precise immunotherapies for IBD beyond broad immunosuppression.
2. TGF-β Signaling, c-Myc Stability, and Targeted Therapy in Osteosarcoma (OS)
- We demonstrated that targeted inhibition of TGF-β type I receptor (via Vactosertib) suppresses OS cell proliferation and significantly reduces established pulmonary metastases in vivo.
- We identified c-Myc as a key downstream effector upregulated by TGF-β in metastatic OS. These findings directly supported Vactosertib’s FDA Orphan Drug Designation (2021), Fast-Track IND approval (2023), and an ongoing international Phase Ib/II clinical trial (NCT05588648) across 21 sites.
- We will investigate the post-translational mechanisms governing c-Myc protein stability in metastatic OS to overcome therapeutic resistance and remodel the immunosuppressive tumor microenvironment.