Research Abstract
The Nissim Lab seeks to understand the signaling and epigenetic changes occurring in the earliest stages of cancer initiation in order to pioneer the first interception strategy for pancreatic cancer. Cancer interception seeks to actively interfere with the earliest events in cancer development in order to prevent progression to more heterogeneous and intractable disease. Effective interception strategies have yet to be identified for most cancers.
Towards this mission, our team leverages zebrafish and mouse models, developmental biology, gene discovery in hereditary cancer patient families seen at DFCI, and integrative transcriptomic, proteomic, and CUT&RUN technologies to answer these questions:
• What are the signaling and epigenetic processes that maintain normal cell identity?
How are these processes disrupted by cancer-initiating mutations?
And, can we reinforce the processes that maintain cell identity to counter pancreatic cancer formation?
• What are the causes of hereditary pancreatic cancer? Families with as many as five cases of pancreatic cancer are suspicious for a heritable etiology, but the genetic basis is not known in most families. While rare, these families offer precious insights into why pancreatic cancer forms. The DFCI Cancer Genetics clinic is an international referral center for such unsolved cancer families. Beginning with families encountered in Dr. Nissim’s clinic, the lab seeks to discover and characterize new causes of hereditary pancreatic cancer.
• GWAS have implicated pathways that modulate pancreatic cancer risk, but underlying mechanisms are not known. Can these pathways be targeted for pancreatic cancer prevention? In particular, the lab is studying the GWAS hit NR5A2, a nuclear receptor that can be pharmacologically targeted, as a potential target for pancreatic cancer prevention.
Dr. Sahar Nissim, MD, PhD, is a physician-scientist who trained at HMS, BWH, and DFCI. For more information about the lab, visit nissimlab.org or email snissim@bwh.harvard.edu.