C-myc deregulation is implicated in the pathogenesis of many tumors. One goal of the proposal is to investigate the non-structural, reversible deregulation of c-myc expression in a murine model system and to determine its importance to human carcinogenesis. An equally important goal is to foster the developing scientific abilities and independence of the applicant. To achieve the first goal, a logical series of experiments based on preliminary data from a model system, has been proposed. In the model system, chronic expression of activated ras is associated with non- structural, reversible deregulation of c-myc. Therefore, the investigation's specific aims are: 1) to identify the molecular mechanism(s) by which c-myc deregulation occurs in the model system; 2) to identify the molecular mechanism(s) by which reversion occurs; 3) to determine the importance of both deregulation and reregulation to human tumors; 4) to begin to investigate the role played by activated ras in non-structural c-myc deregulation. To achieve the second goal, an enthusiastic, dedicated and capable applicant is fortunate to be situated in an outstanding training position. The applicant, who had no experience with basic research prior to the research component of her hematology/ oncology fellowship, has, in a relatively short time, acquired many of the skills required to be a successful and productive scientist, and has demonstrated her commitment to a career with a substantial research component. To become fully independent and compete successfully for research grants, however, she needs additional training, including a mentor who can provide close supervision and a stimulating environment. The sponsor has an excellent record of scientific achievement, both in terms of his own investigations and his ability and commitment to train junior personnel. The laboratory is stimulating and productive. The institution is committed to support basic research in general and this applicant in particular. Awarding a CIA to this applicant would, in the short term, increase our knowledge of c- myc's role in tumorigenesis. In the long term it is likely to increase our understanding of oncogenes and tumor development more generally as the applicant establishes a career as a productive and independent cancer biologist.
