I propose to continue our studies of the myb oncogene and its role in carcinogenesis. In particular, we will further mutate the v- myb oncogene of the avian myeloblastosis virus (AMV) in order to produce altered froms of p48v-myb with which to test the correlation between leukemogenesis and various physical and chemical properties of this protein. We will determine the mechanism by which p48v-myb trans-regulates the expression of other genes, as recently discovered in my laboratory. We will also determine the requirements for leukemogenic activation of the c- myb proto-oncogene by constructing and biologically testing avian retroviruses expressing p75c-myb or altered forms of this protein. In addition we will attempt to identify myb-related genes in lower eukaryotes which are genetically more tractable than birds and mammals. We will also study the comparative moleculaR physiology of myb-related genes in flies and plants. My immediate goals are to continue to pursue a full-time career in cancer research using the latest techniques of molecular and cell biology. This career development award will provide salary support which will free me from clinical, administrative, and teaching responsibilities which I might otherwise have to undertake to support may salary during this critical period in my career. I have operated an independent laboratory studying the myb oncogene for almost three years now and have build a solid core of personnel and equipment to conduct this research. Because I am a """"""""hands on"""""""" principal investigator who spends most of my time physically in the laboratory such salary support is especially important to me. I am currently proposed for a tenure-track appointment as an Assistant Professor of Pathology at the UCSD Medical School effective July 1, 1989, and hope in the long-term to continue my career as a cancer researcher at this institution because of the excellent scientific environment and opportunities for collaboration at UCSD itself, the Salk Institute, La Jolla Cancer Research Foundation and Scripps Clinic and Research Foundation.
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