Modeling mitochondrial disease mutations in cardiovascular systems.

My research program defines how mitochondrial genome structure, stability, and signaling govern tissue-specific function and dysfunction. My group established core principles of nucleoid biology, showing how TFAM compacts mitochondrial DNA (mtDNA) into nucleoids and uncovering the unexpected structural complexity of mammalian mtDNA. This work revealed how mtDNA is packaged, maintained, and destabilized under stress, and led to mechanisms by which mtDNA instability drives cardiometabolic and neurodevelopmental disease. My laboratory now applies these principles in human iPSC-derived tissues to determine how mitochondrial defects evolve into tissue-level failure, including cardiomyocyte dysfunction driven by mtDNA depletion and signaling pathways that shape neurodevelopment. I direct the Center for Metabolism and Mitochondrial Medicine (C3M) and chair the UMDF Scientific and Medical Advisory Board.