Matthew Weitzman Laboratory

Led by Matthew D. Weitzman, PhD, researchers in the Weitzman Laboratory are investigating the molecular relationships between viral infection and cellular DNA damage response (DDR) pathways, as well as studying their contribution to genome instability and cellular transformation/tumorigenesis. The goal of the research in this laboratory is to identify and characterize virally-induced changes that dysregulate DDR pathways, promote genome instability and lead to transformation of normal cells to malignant ones. 

Ongoing studies in the Weitzman Laboratory demonstrated that dysregulation of the human apolipoprotein-B mRNA editing catalytic polypeptide-like (APOBEC3) family of cytidine deaminases can result in mutations and genome instability that could possibly induce cellular transformation of normal cells. Studies found that overexpression of the APOBEC3 family member A3A, induced DNA breaks, activated the DDR and led to cell cycle arrest. Recent work suggests that upregulation of APOBEC3 activity in tumor cells could provide an opportunity for targeted therapy.

Research currently underway in the lab addresses the exact mechanism(s) by which APOBEC3 activity is regulated and how aberrant activity could contribute to human cellular transformation and tumorigenesis. Also, studies are planned to determine if APOBEC3-induced mutations render cancer cells more sensitive to therapeutic agents that block host DNA repair machinery.

Other studies in the Weitzman Laboratory are examining molecular mechanisms by which human viruses harness or inactivate fundamental processes involved in DNA replication and DNA repair. They are focused on ways that viruses manipulate cellular signaling networks, with an emphasis on targets for viral E3 ubiquitin ligases that alter DNA repair pathways and could contribute to our understanding of human cellular transformation and oncogenesis.

Future studies in the Weitzman Laboratory will continue to focus on virus-induced dysregulation of DDR pathways and their contribution to genome instability.