The Jain laboratory team's work is focused on understanding the role of DNA repair proteins in pancreatic ductal adenocarcinoma (PDAC) progression and therapy resistance, with a long term aim to potentially uncover novel therapeutic strategies for this deadly disease.
Role of BARD1 in Pancreatic Ductal Adenocarcinoma (PDAC) Progression & its Mechanism of Regulation
Pancreatic ductal adenocarcinomas (PDAC) are, in general, genetically unstable and highly reliant on DNA repair proteins for survival and evasion from chemotherapeutic exposure. Our lab is particularly interested in understanding the role of DNA repair proteins, specifically BARD1 (BRCA1-Associated-Ring-Domain-1) in PDAC progression and how targeting this protein either alone or in combination with other therapies could prove beneficial for PDAC treatment. We are interested in understanding how BARD1 protects cancer cells from DNA damage and whether it imparts drug resistance. We are also interested in understanding downstream signaling pathways regulated by BARD1 in pancreatic cancers with a hope to uncover novel therapeutic strategies targeting this protein. For our studies, we routinely utilize molecular and cell biology techniques, RNA-sequencing, and animal models of PDAC.
Resistant Mechanisms of PARPi Therapy/Platinums
Poly (ADP ribose) polymerase (PARP) is a DNA repair enzyme that also plays a role in inflammation, regulation of cell death, transcription and modulation of post-transcriptional gene expression. In 2019, olaparib (PARPi) was approved as a maintenance therapy for metastatic PDAC harboring mutations in BRCA1/2. However, emergence of drug resistance is a concern. Our research is focused on elucidating these resistance mechanisms in PDAC using biochemical, molecular and cell biology tools. We have created acquired PARPi resistant models and also have access to patient derived cell line models to conduct our studies.
July 14, 2021