Grant: Project Grant

Cancer, the primary cause of death in our country, initiates through genetic mutations, particularly in DNA repair enzymes like PALB2 and BRCA2. This contributes to genome instability, a characteristic of cancer. While conventional treatments like radiotherapy or chemotherapy induce DNA damage in cancer cells, they have drawbacks, such as causing mutations in healthy cells. Consequently, there's a need for smarter, more efficient approaches in personalized medicine to combat cancer. Success in designing personalized therapies depends on a deep molecular understanding of genetic abnormalities and comprehensive characterization of DNA repair mechanisms. Our research program focuses on two main aspects: the fundamental exploration of DNA repair pathways and the investigation of strategies to manipulate these pathways for therapeutic purposes. The initial two objectives aim to unravel the poorly understood functions of PALB2 and shed light on the consequences of specific mutations in this tumor suppressor. Understanding how PALB2 maintains genome stability during cell division will help design strategies to inhibit its function. The third goal seeks immediate translational outcomes by identifying novel synthetic lethal pathways and inhibitors of PARP and polymerase theta to enhance cancer cell killing in PALB2-deficient cells.