PROJECT SUMMARY/ABSTRACT: Jerry Zifodya, MD, MPH plans to develop an independent research career as a physician-scientist, focused on improving the understanding and outcomes of lung disease in sub-Saharan Africa. The objective of the proposed career development award is to provide necessary training in research methods to facilitate Dr. Zifodya’s transition to independent research. The mentorship available at Tulane University (TU), the University of Washington (UW), and the Kenyan Medical Research Institute (KEMRI) are outstanding. He will continue his work under the mentorship of Drs. Jay Kolls (TU), David Horne (UW), and Kristina Crothers (UW). Collaborators and mentors on his multi-disciplinary research team span the disciplines of tuberculosis (TB) research in Kenya (Dr. Videlis Nduba, KEMRI), global HIV epidemiology (Dr. Patricia Kissinger, TU), TB immunology (Dr. Thomas Hawn, TU), advanced statistics (Dr. Sudesh Srivastav, TU) and bioinformatics (Dr. Yu-Ping Wang, TU). To complement the support from his mentors, Dr. Zifodya will augment his MPH with advanced coursework at the internationally renowned TU School of Public Health & Tropical Medicine and TU Biomedical Sciences Graduate Program. TB is the leading opportunistic infection and primary cause of morbidity and mortality worldwide for people with HIV. Even with adequate treatment of TB, up to half of all persons with pulmonary TB develop post-TB lung disease (PTLD), which is defined by chronic respiratory abnormality after pulmonary TB. The underlying mechanisms of PTLD are unclear. There is a critical need to define the long-term trajectory of PTLD and identify host clinical, immunological, and genetic risk factors. The overall objectives for this proposal are to identify (i) clinical host factors and (ii) host inflammatory and immunological factors that predict PTLD. In preliminary studies we have shown PTLD to be common and associated with elevated inflammatory markers. We hypothesize that upregulation of inflammatory and immune activation pathways after pulmonary TB predicts PTLD and is skewed by HIV (dependent on degree of immunocompromise). We will test these hypotheses in a longitudinal cohort of Kenyan adults with TB with the two specific aims: 1: Determine host characteristics associated with pulmonary function decline and PTLD over 2 years of follow-up in Kenyan adults with and without HIV. 2: Determine whether transcriptomic responses in activated PBMCs can predict impaired pulmonary function and PTLD. This award will provide essential research training in the conduct of longitudinal studies in a low resource setting, measurement and analysis of biomarkers, and interpretation and integration of immunologic data. With the support of this K23, the research and training plan that Dr. Zifodya has devised will assist him in achieving his long-term goal of becoming an independent investigator.