The candidate seeks five years of funding for two career development objectives. The first is for the acquisition of additional skills and training in biostatistics and in the pathophysiology and molecular biology of colorectal cancer along with additional professional, career-development training. The second is for the conduct of a research program in insulin resistance, the IGF axis, and colorectal cancer using data from a wide range of different research projects. The candidate will assemble an advisory committee from among senior faculty colleagues at the University of Minnesota with highly distinguished records of professional achievement in their respective fields with whom he will meet regularly for the purposes of receiving both scientific and professional guidance. The scientific program will focus on three primary research questions: 1. the role chronic hyperinsulinemia and related elements of the metabolic syndrome in the etiology of colorectal cancer, 2. the relationships between the dynamic interactions of the various elements of the IGF axis and the cellular processes involved in colorectal carcinogenesis, and 3. the manner by which the interplay of specific aspects of diet and exercise, through their relationships to obesity, promotes insulin resistance and disturbs the dynamics of the IGF axis. The candidate will explore these hypotheses using five separate research projects. Principal among these are the Polyp Prevention Trial, a multi-centered, randomized trial from which the candidate has serum measures of insulin, glucose, IGF-I, and IGFBP-3 concentrations from 750 participants at three time points in the study;and the CONCeRN Trial, a screening study with a large etiologic component to investigate how a variety dietary and lifestyle factors are related to prevalence of colorectal adenomas. From the CONCeRN Trial the candidate has questionnaire data, serum, DNA, and tissue biopsies from approximately 900 asymptomatic women with complete colonoscopy results. The University of Minnesota provides an excellent environment in which the candidate can pursue both his career development goals and his research objectives through work on these research projects with colleagues at both the University and the National Cancer Institute.
