Research Summary

Genomic instability is a major driving force for tumorigenesis. I am interested in mechanistic molecular studies of proliferation and cell death defects in cancers, partnered with translational studies to identify targeted therapies to modulate the cellular responses to DNA damage and increase cancer treatment efficacy. The proposed research leverages my extensive studies of DNA damage repair in multiple cancer types, as well as my more recent explorations into the role of an emerging oncogene, MTDH. Overexpressed in many solid tumors, MTDH is associated with poor prognosis, metastasis, and resistance to many therapies. My team recently made the novel discovery that MTDH acts as an RNA binding protein to alter translation of many transcripts. This project is focused on MTDH regulation of a subset of these RNA species, specifically the Fanconi anemia DNA repair proteins. We will investigate how MTDH controls mRNA processing including pre-mRNA splicing, nuclear export and translation. These exciting studies will have implications for the many cancers that overexpress MTDH and are resistant to platinum agents. The current focus of my work is to understand molecular mechanisms of MTDH in Fanconi Anemia Repair Pathway to Mediate Drug Resistance.