Research Projects

Chemoresistance is a major cause of treatment failure in oral squamous cell carcinomas (OSCC), with chemotherapeutic regimens like cisplatin, 5FU, and Docetaxel (TPF) being used. Despite initial positive responses, tumors gradually acquire resistance, leading to continued growth and metastatic disease. To overcome drug resistance, reprogramming resistant cells to undergo drug-induced cell death is necessary. Kinases, which regulate various carcinogenesis phenotypes, play a crucial role in regulating these kinases. A preliminary study performed a CRISPR-based kinome screening of 840 kinases in docetaxel resistance cells to identify potential kinases driving docetaxel resistance. Never in mitosis gene A (NIMA)-related kinase 9 (NEK9) was identified as a top hit, and knocking out NEK9 sensitizes chemoresistant OSCC lines to docetaxel. The study aims to validate the findings and explore the potential mechanism by which NEK9 regulates chemoreistance in OSCC. Additionally, a NEK9-based kinase assay will be performed to screen small molecules that inhibit NEK9 kinase activity, potentially restoring docetaxel-mediated cell death in OSCC. The efficacy of NEK9 inhibitors and docetaxel will be evaluated in preclinical animal models.