Lindsey Aubuchon

Program: Cancer Biology

Current advisor: Priyanka Verma, PhD

Undergraduate university: University of North Carolina-Wilmington, 2022

Enrollment year: 2022

Research summary
Targeting ALC1 ATPase activity as a new synthetic lethal approach for BRCA-mutant cancers

Germline mutations in BReast CAncer genes 1/2 (BRCA1/2) significantly increase lifetime risk for the development of various cancer types. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been developed for the treatment of BRCA-mutant cancers; however, the emergence of resistance and severe side effects can occur with the use of these therapies. Therefore, the identification of new therapeutic targets for the treatment of BRCA-mutant cancers are desperately needed to improve treatment options for patients. Genetic depletion of Amplified in Liver Cancer 1 (ALC1) has been previously shown to hypersensitize BRCA-mutant cells to PARPi therapy. Interestingly, my preliminary experiments have shown that loss of ALC1 ATPase activity independent of PARPi leads to decreased viability of BRCA-mutant cancer cells. This highlights that targeting ALC1 ATPase activity can be a new synthetically lethal strategy for BRCA-mutant cancers. My project aims to define mechanistic insights into why ALC1 ATPase loss is synthetic lethal with BRCA-deficiency. Additionally, I will conduct a deep mutational scanning approach to identify key residues that allosterically regulate ATPase activity of ALC1. Together, these studies with provide a strong foundation to develop a new and potent therapeutic strategy for combating BRCA-mutant cancers.

Graduate publications