This K24 application has two broad goals: mentoring junior investigators in patient-oriented research, and expanding a research program in the genetics and prevention of gastrointestinal cancers. The candidate, Sapna Syngal, MD, MPH, is an Associate Professor of Medicine at Harvard Medical School, with dual appointments in the Population Sciences Division of Dana Farber Cancer Institute and the Gastroenterology Division at Brigham and Women's Hospital. She has established a track record at supporting and advancing the careers of physicians pursuing patient-oriented research in gastroenterology and cancer genetics. Her current group of mentees includes five junior faculty members, who currently have NIH research awards or are planning to apply for a NIH grant in the next few months, and four post-doctoral research fellows who are involved in active patient-oriented research projects. Dr. Syngal is also an active faculty member of a variety of NIH training grants, including a T32 in Gastroenterology, a T32 in Genetics, and a R25 in Cancer Outcomes - these training grants will continue to lead to an increasing number of post-doctoral fellows who need close supervision, guidance and mentorship. Dr. Syngal's research program consists of studies that evaluate the impact of human cancer genetics and early detection methods on patient care. These studies use a variety of clinical research designs, including genetic epidemiology, development of clinical prediction models as well as clinical trials. Ongoing projects include (1) Study of optimal methods of identification and management of patients with hereditary colorectal cancer syndromes; (2) The study of novel biomarkers involved in esophageal and colorectal carcinogenesis; (3) Search for the gene for pancreatic cancer; and (4) Study of the optimal management of patients with Li-Fraumeni syndrome. Dr. Syngal is currently the Principal Investigator of an RO1 award and co-investigator on several other multi-center NIH grants. Over the past several years, Dr. Syngal has established herself as a national leader on hereditary colorectal cancer syndrome and a valued mentor for junior investigators interested in pursuing a career in patient-oriented research. PUBLIC HEALTH RELEVANCE: Dr. Syngal's research program continues to provide essential data on phenotypic correlates of inherited mutations, assist in gene-finding endeavors, as well as define the optimal management of individuals at high risk for the development of gastrointestinal cancers. It also contributes to the increasing pool of trained clinical researchers in the field of gastrointestinal cancers and cancer genetics.