Five years of funding are requested to further develop a Center of Biomedical Research Excellence at Kansas University Medical Center with a focus on Nuclear Receptors and their Role in Liver Health and Disease. Five talented new faculty who share this research interest were selected with the goal of helping them become funded, independent investigators. A PI, co-PI, an internal advisory committee of experienced senior faculty and an external advisory committee of prominent scientists have been assembled to mentor them to this goal. The Center will also help provide infrastructure and equipment to supplement the research environment. Ultimately, through the achievement of these initial goals, the final long-range goal is the submission of a program project grant application. An important feature of this Proposal is that for each initial junior faculty member, two co-mentors have been assigned and individual mentoring plans and timetables have been developed. Central features of the mentoring plans include ongoing critical evaluation of the research project by the mentors and IAC, semiannual conferences with EAC members, and special training on statistics, manuscript and grant writing, and teaching. The first 6 junior faculty assigned to this COBRE have competed successfully for independent NIH R01-type research support. The same is expected of the present junior faculty. Once the present junior faculty are funded externally, they will financially rotate off the grant to make room for addition of new junior faculty members. Another important feature of the Proposal is to maintain 4 research Cores to provide additional research support for the Center's faculty. These cores include an administrative Core as well as Cores in the areas of biospecimen, histopathology, analytical, and sequencing. In summary, the outstanding combination of scientific talent, existing research environment, and new core facilities ensure that this proposed Center will further foster the development of a thematic multidisciplinary research center, to enhance the ability of new investigators to compete independently for complementary NIH and other external peer-reviewed support, and to strengthen existing biomedical research infrastructure at KUMC.