This proposal is a revision of a Physician Scientist Award. The objective of the program is to provide the applicant with a structured educational experience in molecular biology that will train her for independent career in academic medicine. Her developing knowledge and laboratory experience will be applied to the isolation and characterization of the Gorlin syndrome gene, a probable tumor suppressor that is important in normal embryogenesis and development. Her sponsor, Dr. Allen Bale, is an Assistant Professor in the department of Genetics with a long standing interest in cancer predisposition syndromes and the role of cancer related genes in development. The program has been divided into two phases according to the guidelines for the K11 award program and will be completed over a period of five years. The didactic program of Phase I will include laboratory meetings, lectures in the Department of Genetics, and formal course work on statistical genetics, cytogenetics, molecular biology of eukaryotic cells, developmental biology, and advance topics in molecular genetics. Her research during this phase will include screening a chromosome 9 microdissected library for new STRs mapping to the Gorlin syndrome region, tumor deletion mapping with the new probes, and construction of a YAC contig of the region. The transition from Phase I to Phase II will consist of an oral exam and formal presentation of research progress to the advisory committee. During Phase II the great bulk of the applicant's time will be spent in the laboratory, and emphasis will be placed on developing self confidence and independence in the use of sophisticated scientific methodology. She will continue to construct a YAC contig and isolate candidate cDNAs from the contig, as well as isolated expressed sequences from the microdissected library. Ultimately she will test the candidate genes by analyzing their expression in tumor and normal tissue and searching for mutations in Gorlin syndrome patients.
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