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The Impact of MEN1, DAXX, ATRX, and PTEN in Pancreatic Neuroendocrine Cancer Pathogenesis
Dr. Wong's laboratory specializes in integrating genomic information with relevant mouse models to study novel treatments with the ultimate goal of moving new treatments into clinical trials for patients.
Previous CFCF-funded researchers discovered mutations in the genes ATRX and DAXX among tumors from patients with non-functioning pancreatic neuroendocrine tumors. Despite these exciting and promising findings, the precise role of ATRX and DAXX in neuroendocrine tumor development is yet to be understood and treatments exploiting these findings have yet to be developed. Furthermore, researchers do not have the research tools, including mouse models, they need to develop new therapies for patients.
In this project Dr. Wong will create the mouse models necessary to determine the impact of recently identified mutations in neuroendocrine tumor development. Next Dr. Wong will conduct experiments using his mouse models to identify the cellular pathways that are deregulated as a result of these mutations. Any pathways identified represent potentially new and novel therapeutic targets for treatment of patients with neuroendocrine tumors.
Dana-Farber Cancer Institute
Kwok-Kin Wong M.D., Ph.D.
- Create mouse models to determine the impact of the genes: MEN1, DAXX, ATRX, and PTEN in pancreatic neuroendocrine tumor development.
- Determine the epigenetic and expression profiles of the mouse pancreatic islet cells derived from these mouse models.
The roles of several genes found to be frequently mutated in non-familial pancreatic neuroendocrine cancer are mostly unknown. In this project, Dr. Wong's laboratory will introduce these mutations specifically in mouse pancreatic cells and study how these mutations might cause neuroendocrine tumors to develop.
This project will: generate models to test new, targeted therapies for patients; and identify genes and pathways that can be targeted to develop new therapies for patients.