Lipid signaling in cardiac development and disease

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PROJECT SUMMARY This proposal contains a detailed five-year training program for mentored career development of a underrepresented minority in biomedical research, with a focus on cardiovascular disease and lipid signaling. The Applicant has completed training in cardiovascular development and stem cell biology and is proposing a research direction specifically designed to provide additional essential training for his transition towards an independent academic research career. Through the career and scientific plans contained in this proposal, the Applicant aims to leverage his prior training in stem cell biology and cardiac development, with newly acquired skills in mass spectrometry-based lipidomics, large-dataset analysis, high-content screening and cardiovascular disease models within a well-structured and mentored scientific environment, in order to understand the eicosanoid changes that occur in cardiomyocytes during heart development and disease. A joint mentorship has been established between Dr. Mohit Jain, an expert physician-scientist at the University of California San Diego with expertise in metabolomics, systems analysis and genomics, and Dr. Ju Chen, a world expert in stem cell biology, cardiac physiology and disease, to foster the Applicant's scientific and career development. Dr. Jain's and Dr. Chen's laboratories will provide an excellent environment for the applicant, with state-of-the-art infrastructure, analytical skills and innumerable resources required to obtain the necessary training. Both Dr. Jain and Dr. Chen have a proven track record of mentorship, including young investigators transitioning to faculty positions or as independent researchers. The Applicant has put together an expert academic advisory committee of distinguished scientists and clinicians from UCSD and external research communities to guide and complement each other's scientific expertise. Furthermore, the Applicant has also enlisted the advisory support of Dr. Mark Lawson, from UCSD, for training in equity and integration of minorities underrepresented in biomedical sciences. The central goals of this proposal are to 1) investigate activation of the eicosanoid pathway during cardiac stem cell differentiation and heart development, 2) identify specific eicosanoid species that drive cardiomyocyte differentiation, and 3) explore the contribution of eicosanoid signaling pathways in heart failure. The Applicant will utilize an innovative mass spectrometry- based eicosanoid profiling platform, together with in vitro high-content analysis tools, systems analysis, state- of-the art stem cell differentiation techniques and in vivo mouse models of heart development and cardiac disease. These aims will serve to integrate discovery approaches and hypothesis-driven research. The experience obtained from the proposed training and career development will serve as the basis for the Applicant's independent career as scientist.