2019 Grantee: Xiaochun Yu, MD, PhD
Beckman Research Institute of the City of Hope
Research Project: Targeting dePARylation for Pancreatic Cancer Treatment
Award: 2019 Pancreatic Cancer Action Network Translational Research Grant
Award Period: July 1, 2019 – June 30, 2021
Dr. Yu received his MD from Beijing Medical University in China and PhD from Kurume University in Japan. He did research fellowship training at Mayo Clinic from 2002 to 2006. Dr. Yu established his laboratory at University of Michigan Medical School in 2006. From 2006 to 2015, Dr. Yu was promoted from assistant professor to full professor. In 2015, Dr. Yu moved to City of Hope.
The research interests from Dr. Yu’s laboratory focus on DNA damage repair and its role in tumor suppression. His group not only examines the underlying molecular mechanism but also translates the basic research findings into clinical cancer treatment. Dr. Yu has received several awards such as American Cancer Society Research Scholar, Department of Defense Era of Hope Scholar and Leukemia and Lymphoma Society Research Scholar.
Normal cells in the body, including ductal cells and acinar cells of the pancreas, encounter DNA damage on a daily basis. However, healthy cells have precise mechanisms to repair damage to DNA. Genetic mutations can stop DNA damage repair (DDR), which causes genomic instability and can lead to tumor formation. Thus, a subset of pancreatic cancer is defective in DDR.
Recently, accumulated evidence shows that drugs called PARP inhibitors, which block a process called poly(ADP-ribosyl)ation, selectively kill tumor cells with DDR defects, such as mutations in BRCA 1 or 2 or similar-acting proteins. Several PARP inhibitors have been approved by the FDA for the treatment of advanced breast cancer and ovarian cancer with BRCA mutations.
However, the efficacy of PARP inhibitors in pancreatic cancer treatment remains elusive. One of the reasons is that currently available PARP inhibitors may not be able to fully shut down poly(ADP-ribosyl)ation-mediated DDR in pancreatic cancer cells. However, based on Dr. Yu and his team’s preliminary studies, they find dePARylation is a key event during DDR. Thus, in this application, they plan to characterize the role of dePARylation in DDR and develop a novel chemotherapeutic approach to target dePARylation for pancreatic cancer treatment.