Dr. Khalili is an established investigator and mentor as evidenced by her high-quality patient-oriented research, mentoring activities of young investigators, and her institutional leadership roles in research mentoring. Her long-term career objectives are: 1) to support and train early clinical investigators to transition to independent careers in multidisciplinary research, 2) to enhance effectiveness of research mentors to better meet the needs of their mentees, and 3) to lead efforts in better understanding of mechanisms of host and environmental interactions important to pathogenesis and progression of liver disease. During the next project period, she will use initial successes of the last project period to further expand her research and mentoring program, thereby increasing the pool of new investigators that successfully transition to independence. Dr. Khalili's multidisciplinary research program supported by continuous extramural funding will serve as the platform for providing mentorship for junior investigators from different disciplines. Moreover, she plans to lead national training efforts to enhance research mentor and mentee self-efficacy and mentee productivity especially among underrepresented groups in biomedical sciences. In the next project cycle she will capitalize on the rich academic environment of UCSF and its Clinical and Translational Sciences Institute resources to train mentees from different disciplines to enable them to compete successfully for mentored career development and independent awards in patient-oriented research. While the value of mentoring has been well-established, better understanding of which components of mentoring are most impactful on mentee success and implementing these strategies in training mentors are also critical to their young investigator career development. Dr. Khalili will use her leadership role in the UCSF Mentor Training Program to advance mentor training approaches through evaluation and program enhancement that build capacity of research mentors to effectively mentor young investigators and especially those from underrepresented backgrounds. Insulin resistance is an important contributor to negative impact of chronic liver diseases on human health and adipose tissue dysfunction has emerged as important to pathogenesis of liver disease. During the first project period, we gained insights into host, alcohol, and viral interactions influencing pathogenesis of abnormal glucose metabolism. The research plan for the next project period will extend these investigations to evaluate the influence of alcohol on adipose-tissue liver axis using chronic hepatitis C as a model of a common liver disease with high rates of adverse metabolic outcomes and in utilizing validated and direct measurements of insulin resistance in adipose tissue in at-risk populations. This research plan and resources from Dr. Khalili's ongoing research activities will provide mentoring and training opportunities for new and junior clinical investigators in patient-oriented multidisciplinary research in liver disease. The continuation of this award will allow Dr. Khalili to achieve these mentorship and research goals.