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Seung Kim, M.D., Ph.D. - Stanford University
Associate Professor in Developmental Biology at Stanford University
"We propose to generate mouse models of carcinoid using conditional genetics. These mouse lines will permit investigation of tumor pathogenesis and create tumor-derived cell lines. Collectively these novel reagents will facilitate genomic, physiologic, and pharmacologic studies of carcinoid."
The study and treatment of human diseases has benefited enormously from the development of animal disease models, but such models are lacking for the classic form of human carcinoid. Thus, we are motivated to create new carcinoid models using the mouse, a laboratory animal for which powerful genetic tools have been developed. Carcinoid tumors are neuroendocrine (NE) tumors, and prior studies have revealed that the Tag oncogene is sufficient to produce NE tumors at multiple sites in mice. By activating the Tag oncogene only in neuroendocrine cells of the gastrointestinal and pulmonary tracts, we aim to direct tumor formation at specific locations where carcinoids are known to develop. Our strategies for producing carcinoid in mice would allow us to control the timing and location of tumor formation. Creation of these mice should be useful for isolating carcinoid cells, which will facilitate studies of tumor cell genetics and physiology. These cells and the mice should prove valuable for identifying signals that regulate carcinoid growth, and for testing candidate compounds for activity in arresting carcinoid tumors.
Dr. Kim explored the use of mice to reconstruct tumors resembling carcinoids with a goal to produce a carcinoid cell line. His strategy was based on prior successful creation of tumors and tumor cell lines from a variety of mouse hormonal cells in the intestines and pancreas. He used a genetic approach based on the idea that carcinoid likely originates from specific intestinal cells producing the TPH gene. Thus far, Dr. Kim has not produced useful tumors or tumor cell lines resembling carcinoid, but is continuing this approach, even after cessation of funding from CFCF.