This application presents a 3-year predoctoral support structure for the training and research experience of the applicant, Mr. Ian Mathews, centered around identifying and characterizing small molecule mediators of cancer immunotherapy outcomes. Through a detailed training plan under sponsor Dr. Sonia Sharma and co-sponsor Dr. Mohit Jain, the applicant will pursue enrichment in human metabolomics, large scale biostatistics, tumor immunology, academic networking skills, and scientific rigor and ethics. Uniquely positioned between the University of California San Diego (Dr. Jain) and the La Jolla Institute for Allergy and Immunology (Dr. Sharma), this proposal interrogates a multidisciplinary academic niche. This highly specialized breadth of experiences, with dedicated guidance from both sponsor and co-sponsor, allows for the applicant?s enrichment as few other graduate student experiences can provide. Both mentors have a proven track record of collaboration and publication, a proven track record with academic trainees, and are resolutely dedicated to supporting the applicant in the pursuits of this proposal and his greater academic career. The applicant aims to 1) validate several newly identified predictive and dynamically regulated small molecule metabolites detected in biosamples from human immune checkpoint inhibitor patients; these metabolites strongly associate with the development of immune related adverse events (irAEs) in the patients, and 2) determine the functional role of these molecules in setting of deleterious chronic inflammation similar to the phentoypes of the patients. In pursuit of these goals, the applicant will utilize state-of-the-art, high throughput techniques in liquid chromatography-mass spectrometry (Jain), as well as novel, clinically relevant models of irAE inflammation and anti-tumor immunity (Sharma). Taken together, these training experiences, direct and fulfilling mentor relationships, and innovative research designs will serve as an invaluable foundation for the applicant?s future post-doctoral academic career.
Using a powerful unbiased technique called state of the art, untargeted metabolomics, this proposal aims to measure and identify small molecule metabolites associated with immune related adverse events (irAE) in solid tumor cancer patients undergoing cancer immunotherapy in the form of immune checkpoint inhibitors. This proposal will identify novel small molecules that may serve as biomarkers of irAE incidence and modulators of immunotherapy-derived autoimmunity without limiting therapeutic efficacy.!This F31 award will provide for the applicant an unparalleled research and training experience, under the invested and dedicated guidance of Dr. Sonia Sharma (primary sponsor) and Dr. Mohit Jain (co-sponsor).