Cardiomyopathies are serious medical conditions with significant morbidity and mortality. This proposal provides a mechanism for achieving an immediate career goal of expanding the candidate's scientific skills to the fields of mouse genetics and energy metabolism and for continuing his interests in cardiomyopathies. The candidate has a Ph.D. in molecular genetics. He is an Assistant Clinical Professor in Pediatrics, Division of Medical Genetics. He has a long-standing and continued interest in a career in academics and in the etiology of human genetic diseases. He has pursued relevant clinical and research training with a long term goal of contributing to the understanding of the molecular mechanisms of human development anddisease pathogenesis. Through the utilization of the mouse model system in the analysis of cardiogenesis and metabolism, the candidate will thereby obtain tools to gain greater insight into similar human conditions. Research will focus on one type of cardiomyopathy, noncompaction of the ventricular myocardium, and mitochondrial dysfunction. As the mitochondrion is essential for cardiogenesis and function by providing energy and regulating apoptosis, mitochondrial dysfunction may play an essential role in disease pathogenesis. The goal is to understand the pathophysiological mechanism of this condition using an animal model and studies in patients.
The specific aims i nclude: (1) examining cardiac-specific mitochondrial pathophysiology in mice deficient in the adenine nucleotide translocator isoform 2 (Ant2), a key mitochondrial membrane protein and (2) identifying the specific gene causing the condition on human chromosome 11. These studies will provide valuable insight into cardiomyopathies leading to a greater understanding of the underlying pathophysiology. The environment in which this study will be performed is well-suited for facilitating the applicant's career development plan as the Department of Pediatrics and the Center for Molecular and Mitochondrial Medicine and Genetics at UCI provides the candidate with expertise in the areas of mouse genetics, mitochondrial metabolism, developmental biology, advanced imaging microscopy and interdepartmental collaborations. Through the combination of supervised research, scientific exchange and selected coursework, the applicant will obtain the training necessary for a successful transition to an independent investigator.
