Lab
Nissim Lab
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Statement of Research Interest
Pancreatic cancer is one of the most deadly cancers, with notoriously ineffective treatment options. Our research group leverages developmental biology, genetic discovery in hereditary pancreatic cancer families, transcriptomic and proteomic approaches, and pre-clinical studies in zebrafish and mouse models to characterize novel determinants of cancer initiation and develop strategies for prevention and treatment of pancreatic cancer.
In about 10% of cases, pancreatic cancer occurs as multiple cases in a single family, raising suspicion of a hereditary cause. The explanation for most of these families has not been identified. Finding and understanding the genetic basis of “unsolved” pancreatic cancer families can help identify who is at risk and should have surveillance in the family. More broadly, understanding how a single inherited mutation leads to pancreatic cancer can gives us precious clues into why the cancer happens and new strategies for treatment and prevention. To address this need, the Nissim Lab has developed a research pipeline for discovery, validation, and characterization of new genetic causes of hereditary pancreatic cancer. By whole genome sequencing analysis, we can identify inherited mutations associated with pancreatic cancer in multiple family relatives. To validate the causality of these mutations in cancer, we assess how these mutations impact cancer risk in zebrafish populations. To characterize these novel cancer pathways, we interrogate function in the context of zebrafish pancreas development in conjunction with unbiased transcriptomic and proteomic approaches. As a proof-of-principle, we recently identified the cause of pancreatic cancer in a previously-unsolved family with 5 cases, validated the causality of this mutation in zebrafish populations, and discovered that the mutation alters the intracellular trafficking of KRAS (Nissim et al., Nature Genetics, 2019). We are now exploring the therapeutic potential of targeting this pathway in pancreatic cancer.
Sitting at this intersection of longitudinal care of hereditary pancreatic cancer families in the clinic, genome analysis, and zebrafish cancer models at the lab bench, our research group is well-positioned to continue making pivotal discoveries that will advance our understanding and management of pancreatic cancer.
In about 10% of cases, pancreatic cancer occurs as multiple cases in a single family, raising suspicion of a hereditary cause. The explanation for most of these families has not been identified. Finding and understanding the genetic basis of “unsolved” pancreatic cancer families can help identify who is at risk and should have surveillance in the family. More broadly, understanding how a single inherited mutation leads to pancreatic cancer can gives us precious clues into why the cancer happens and new strategies for treatment and prevention. To address this need, the Nissim Lab has developed a research pipeline for discovery, validation, and characterization of new genetic causes of hereditary pancreatic cancer. By whole genome sequencing analysis, we can identify inherited mutations associated with pancreatic cancer in multiple family relatives. To validate the causality of these mutations in cancer, we assess how these mutations impact cancer risk in zebrafish populations. To characterize these novel cancer pathways, we interrogate function in the context of zebrafish pancreas development in conjunction with unbiased transcriptomic and proteomic approaches. As a proof-of-principle, we recently identified the cause of pancreatic cancer in a previously-unsolved family with 5 cases, validated the causality of this mutation in zebrafish populations, and discovered that the mutation alters the intracellular trafficking of KRAS (Nissim et al., Nature Genetics, 2019). We are now exploring the therapeutic potential of targeting this pathway in pancreatic cancer.
Sitting at this intersection of longitudinal care of hereditary pancreatic cancer families in the clinic, genome analysis, and zebrafish cancer models at the lab bench, our research group is well-positioned to continue making pivotal discoveries that will advance our understanding and management of pancreatic cancer.
Lab Members