Research Projects

Necroptosis is a crucial regulated cell death mechanism in cancer biology, eliciting strong adaptive immune responses to defend against tumor progression. However, it can also promote tumorigenesis and cancer metastasis by promoting an immunosuppressive tumor microenvironment. The role of the necroptosis pathway in the progression of oral squamous cell carcinoma (OSCC) is not fully explored. Recent data shows that approximately 50% of necrosis in tumors occurs through necroptosis. Preliminary data also showed upregulation of necroptosis in OSCC in mice, and treatment with RIPK-1 inhibitor attenuated cancer progression. This study aims to understand the functional role and therapeutic potential of the necroptosis pathway in OSCC progression. The main experiments involve studying the expression of necroptosis pathway markers in human OSCC, generating mouse oral cancer cells deficient in RIP-1 and RIP-3, evaluating the effect of depletion of RIP1 and RIP3 on OSCC progression in mice, understanding the impact of RIP1 and RIP3 on various cancer-associated pathways, and treating mice bearing OSCC with RIP1, RIP3 inhibitors as monotherapy or in combination with checkpoint inhibitors. The proposed study will provide proof of concept and mechanistic explanation for targeting necroptosis in OSCC, help understand the therapeutic potential of necroptosis inhibition in OSCC progression, and identify molecular pathways regulated by RIP1 and RIP3 in the context of OSCC pathogenesis through transcriptome analysis.