The mission of the Center for Cancer Research Development is to coalesce and foster outstanding, interactive, laboratory-based cancer research centered on the Molecular and Cellular Pathogenesis of Cancer. To this end, three program projects, each with two subprojects will be initiated in year one along with four pilot projects, the latter supported by funds from Rhode Island Hospital/Academic Medical Center (RIH/AMC). The goal will be to develop program projects in four different but related themes, into interactive research groups composed of at least 3 junior investigators supported by peer reviewed grants. This will be accomplished by establishing and perpetuating an intellectually dynamic training environment in which junior investigators will create and disseminate new knowledge and clinical applications and with the guidance of senior faculty mentors, build nationally competitive, independent, but interactive research programs. The investigators will utilize common model systems and state-of-the-art core facilities in administration, career development, proteomics and molecular pathology to 1) discover mechanisms leading to neoplasia and 2) develop clinical applications resulting from this knowledge. The six subprojects, mentored by a team of seven senior faculty including the PI and Co-PI, target programmatic themes in gastrointestinal cancer, developmental proteins and intracellular signaling pathways. A fourth theme in viral mechanisms of carcinogenesis is represented by pilot projects funded by the institution. The proposal represents a strategic partnership in which RIH/AMC will commit significant resources to supplement those requested in this application to build cohesive strength in basic cancer research that complements existing strengths in clinical cancer treatment, outreach, and prevention. The long-term goal of this support is to achieve NCI designation as a Comprehensive Cancer Center. Guidance for the Center will be provided by teams of Internal and External Advisors and Consultants including a Translational Research Group together with a carefully considered plan of training, evaluation and succession. The end result will be a Cancer Research Center of investigators with significant programmatic strengths and translational impact.