2021 Grantee: Aditi Jain, PhD
Thomas Jefferson University
Research Project: Targeting BARD1 in Pancreatic Ductal Adenocarcinoma
Award: 2021 Pancreatic Cancer Action Network Career Development Award
Award Period: July 1, 2021 – June 30, 2023
Dr. Jain is currently a Research Instructor within the Department of Surgery at Thomas Jefferson University. In 2007, she completed her undergraduate studies in Pharmacy at University of Delhi, India. In 2008, she moved to United States to pursue her PhD in Pharmaceutical Sciences with a focus in Cancer Biology at Idaho State University in Pocatello, Idaho. Dr. Jain later completed two postdoctoral fellowships, one at University of Kentucky and a second in the laboratory of Dr. Jonathan Brody, a two-time PanCAN grantee, at Thomas Jefferson University. During her postdoctoral training in Dr. Brody’s laboratory, Dr. Jain became interested in studying DNA repair proteins in pancreatic cancer.
Since her appointment as a Research Instructor in 2020, she has been working in the Jefferson Pancreas, Biliary and Related Cancer Center, and in the newly founded Pancreatic Cancer Research Institute (PCRI). Dr. Jain’s current research involves understanding the role of BARD1 (BRCA1-Associated Ring Domain 1) in pancreatic cancer growth, progression and therapy resistance with a focus on targeting this protein and potentially uncovering novel therapeutic strategies for this deadly disease.
Over the last 50 years, only marginal improvement in patient outcomes have been achieved, and despite tremendous research efforts, available therapeutic options for pancreatic cancer patients remain unsatisfactory. This underscores a huge unmet need for better and more effective therapies. Deleterious mutations in DNA repair genes like BRCA1/2 offer new therapeutic opportunities that have been recently explored with the use of PARP inhibitors and platinum-based chemotherapies. Although promising for a subset of pancreatic cancer patients, the relative rarity of BRCA defects in pancreatic cancer limits the application of these promising strategies.
Therefore, exploring DNA repair targets beyond BRCA1/2 is crucial. Dr. Jain and her research team’s goal is to target BARD1 (BRCA1-Associated Ring Domain 1), a DNA repair protein that functions with BRCA1 and evaluate how targeting BARD1 enhances sensitivity of pancreatic cancer cells to DNA damaging drugs, like PARP inhibitors and platinum drugs and others, with the hope to find novel therapeutic combinations for deadly pancreatic cancers. They also aim to understand a novel mechanism of BARD1’s regulation in pancreatic cancer that has not been yet explored. For this proposal, the team will utilize mouse models of pancreatic cancer, pancreatic cancer cell lines, patient-derived samples and DNA damage drug libraries.
Conceptually, this study is of importance since pancreatic cancer cells are highly reliant on DNA repair proteins to survive and evade effects of chemotherapy, and Dr. Jain proposes to tap into this vulnerability by targeting BARD1. Accomplishment of these studies will not only establish BARD1 as a therapeutic target in pancreatic cancer and unravel novel combinatorial strategies for the treatment of these deadly pancreatic cancers, but also enhance understanding of an important mode of gene regulation of this target. The overarching goal of this proposal is to find novel therapeutic combinations which hold promise for improving patient outcomes.