Jeffrey R. Smith, MD, PhD


Associate Professor, Department of Medicine; Division of Genetic Medicine

Research Description

Our research group investigates genetic predisposition to cancer, with parallel goals of elucidating causality and contributing to personalized medicine. We apply state-of-the-art genomics technology and custom bioinformatics in large-scale projects of breast and prostate cancer. We have also contributed genomics tools for the zebrafish model organism. The breast cancer project is a collaborative study with Dr. William Dupont to determine genetic causes of breast cancer within the Nashville Breast Cohort (NBC) and additional breast cancer study populations. The NBC is a cohort of 8000 women with benign forms of breast disease who have been followed for over two decades for the development of invasive breast cancer. The cohort enables investigation of genetic, epidemiologic, and pathologic factors in the progression of premalignant breast lesions to invasive breast cancer. Our prostate cancer project investigates genetic causes of familial prostate cancer. Prostate cancer has the largest heritable risk of all common cancers, but relatively little is known about the underlying genetic etiology. The study population is comprised of 1000 prostate cancer cases with a family history the disease, and 1000 controls without any personal or family history of prostate cancer (comparing those in the extremes of the distribution of genetic load for prostate cancer). A third project has developed genetic mapping resources for the zebrafish vertebrate model organism. We identified 1.2 million SNPs, developed a high-resolution genetic map, and characterized the diversity and ancestry of common strains. As an example of the utility of the resource, we demonstrated that sex determination in zebrafish is a complex trait, not involving sex chromosomes.