The overarching goal of my research program is to understand the molecular mechanisms of immune surveillance mediated by tissue-resident memory T cells that patrol the mucosal barrier of the lungs to control infectious diseases and cancers. My laboratory is best recognized for its contributions to the cell biology and biochemistry of MHC and MHC-like CD1d molecules. These molecules play important roles in protein and lipid antigen presentation and, thereby, control T cell and natural killer T (NKT) cell biology, respectively. In recent years, our research focus has turned toward harnessing what we have learnt in basic immunology to augment immune reaction through vaccine and adjuvant design to prevent or treat microbial infections and cancer, deathly diseases that ail humankind: We recently reported a strategy for CD8+ T cell-targeted vaccine design to identify targets that confer protective immunity against poxvirus disease (J. Clin. Invest. 123: 1976— 1987;; 2013). Using this model, we have elucidated the mechanisms of induction, maintenance and action of tissue resident memory (Trm) CD8+ T cells and how Trm cells impart lung/pulmonary mucosal immunity (Cell Rep 16: 1800;; 2016). New work supported by the Research Career Scientist and the VA Merit will refine the above strategies to devise ways to identify, characterize and develop vaccine candidates against tuberculosis. Aims of this project are, (a) to identify T cell epitopes that will protect against pulmonary M tuberculosis infection in a preclinical humanized mouse model;; (b) to identify globally protective epitopes that cross MHC restriction barriers;; and (c) to characterize nanoparticle-based delivery systems for intracellular STING- targeted adjuvant and antigen delivery. Hence, as a Research Career Scientist, I hope to identify T cell epitopes that will protect against tuberculosis and devise ways to enhance immunological memory at the lung mucosal surfaces by vaccinating with subunit vaccines and intracellular adjuvants. This outcome will impact clinical management of tuberculosis as well as other respiratory infectious diseases and cancers. My research program was developed through numerous collaborations with investigators at the VA, the University Affiliate, the NIH, and at national and international institutions. I have published over 120 articles, several in top-tier journals. These works have been cited over 9,700 times, and have an h-index of 48 and an i10-index of 93. Significantly, our research has been continuously supported by federal grants over the last 20+ years and by a VA Merit Award over the last four years. In sum, I am well-poised to serve our Veterans as a Research Career Scientist. Through this appointment, I hope to enhance research in vaccines and vaccine delivery mechanisms that will utilize T cell epitopes. The emerging vacc...