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Mouse Model Project Using Forward Genetics
"The development of more effective treatment regimens for patients with carcinoid metastasis and carcinoid syndrome has been hampered by the lack of effective in vivo models, which recapitulate the disease process in humans." - Dr. David Tuveson
Dr. Tuveson's laboratory will use their expertise in forward genetics and mouse cancer modeling to mutagenize enterochromaffin cells, enteroendocrine cells found in the digestive and respiratory tracts, to both generate models of carcinoid cancer and simultaneously identify genes and pathways that promote carcinoid cancer formation.
The lack of model systems that accurately recapitulate the behavior of neuroendocrine cancers has long been a significant hurdle to developing targeted treatments for patients. This project has the promise to create faithful animal models; therefore, eliminating one of the barriers to treatment development.
Cold Spring Harbor Laboratory
David Tuveson M.D., Ph.D.
- To generate the first accurate mouse models of neuroendocrine tumors
- To identify genes and pathways that cause neuroendocrine tumor formation following transposon-mediated mutagenesis in adult enterochromaffic cells
Patients with neuroendocrine tumors (including carcinoid) have few therapeutics options besides surgery and investigational agents, and this is a frustrating reality in my clinical practice when I encounter such patients. Currently, there is no suitable animal model that recapitulates the human diseases to allow the development of new medical interventions for neuroendocrine tumors. Also, the cause of neuroendocrine cancer has been difficult to establish from previous studies of clinical specimens. In this application, I proposed to develop mouse models of neuroendocrine cancer by taking advantage of a new method of generating tumor models with "jumping genes" that are called transposons. Any neuroendocrine tumors that develop in such mice will then be studied to quickly determine the genes that cause neuroendocrine tumors, and this information will both be useful to determine the cause of neuroendocrine tumors and to establish reproducible models of neuroendocrine tumors for the field. This proposal will involve the training of a new physician scientist to facilitate the development of an independent neuroendocrine cancer specialist.
This project will generate models researchers need to test potential new therapies for patients, identify genes and pathways that are involved in neuroendocrine tumor development, and allow a young physician scientist to pursue a career in neuroendocrine tumor research.