GRANTEE: Rohit Chandwani, MD, PhD
Memorial Sloan-Kettering Cancer Center
Research Project: The Epigenetic Plasticity of Pancreatic Adenocarcinoma
Award: 2016 Pancreatic Cancer Action Network – AACR Pathway to Leadership Grant
Award Period: July 1, 2016 – June 30, 2021
A native of New York, Dr. Chandwani attended college at Harvard University, graduating magna cum laude with a degree in economics. He then went on to medical school at Yale University, followed by residency training in general surgery at Columbia University Medical Center. During residency, Dr. Chandwani completed his PhD at The Rockefeller University, studying chromatin end epigenetics in the immune system. After completion of surgical residency, Dr. Chandwani joined the surgical oncology fellowship program at Memorial Sloan-Kettering Cancer Center, where he was named chief fellow and now remains as a postdoctoral fellow in the laboratory of Dr. Steven Leach. Dr. Leach also received a research grant from the Pancreatic Cancer Action Network and is the chair of our Scientific and Medical Advisory Board.
The most common form of pancreatic cancer, pancreatic ductal adenocarcinoma, was named to reflect the longstanding hypothesis that pancreatic tumors arise from ductal cells within the pancreas. However, increasing recent evidence has suggested that pancreatic tumors actually arise from a different cell type, called acinar cells, which take on ductal-like characteristics through a process called acinar-ductal metaplasia (ADM).
Surprisingly, the genetic sequence of the DNA in cells that have undergone ADM is not different from the original acinar cells. Therefore, Dr. Chandwani proposes that cells are subject to “epigenetic” changes that lead to their transition from acinar to ductal subtypes. Epigenetics refers to the physical structure, packaging and location of DNA and its interacting protein partners. Epigenetics directly affects the timing and expression of genes without changing the DNA sequence itself. To further strengthen Dr. Chandwani’s hypothesis, recent studies have identified frequent mutations altering the activity of proteins involved in epigenetic regulation in pancreatic cancer cells.
The first goal of Dr. Chandwani’s project is to assess the structure of the epigenetic DNA/protein machinery in acinar and ductal cells of the pancreas. He and his research team will next identify epigenetic changes that occur as normal cells of the pancreas are transformed to precancerous (pancreatic intraepithelial neoplasm, or PanIN) and cancerous states. Finally, Dr. Chandwani and his colleagues will look at the mutations of proteins involved in epigenetic regulation of pancreatic cancer cells, with the goal of determining whether their activity can be blocked as a therapeutic strategy.