2019 Grantee: Yilun Liu, 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. Liu is a professor and associate chair in the department of cancer genetics & epigenetics. She received her BS from Massachusetts Institute of Technology (MIT) in 1995 and her PhD in molecular biophysics & biochemistry from Yale University in 2000, where she held a four-year Howard Hughes Medical Institute Predoctoral Fellowship. Following her PhD, she was awarded an American Cancer Society Postdoctoral Fellowship and Breast Cancer Campaign (UK) Postdoctoral Fellowship to pursue her postdoctoral training at Clare Hall Laboratories of Cancer Research UK. Following an assistant professorship in the department of therapeutic radiology at Yale University School of Medicine from 2006-2011, she joined City of Hope as an associate professor and associate chair in 2011 and was appointed full professor in 2018.
Her research has been focusing on understanding how dysfunctions in DNA replication, transcription and DNA repair contribute to genomic instability that leads to cancer and premature aging. Dr. Liu’s work has also been recognized by her appointment to multiple National Institutes of Health (NIH) study sections and a history of successful extramural funding. In addition to leading an active research laboratory, Dr. Liu is also serving as the Vice Dean of the Irell & Manella Graduate School of Biological Sciences at City of Hope.
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. Liu and her 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.