Our laboratory studies how energy metabolism and cellular substrate preference can regulate cell function and fate. Much of our interest centers on mitochondria, organelles chiefly responsible for energy transduction but also involved in biosynthesis, ion and metal homeostasis, redox balance, and signal transduction. Rather than focus on a specific disease or pathology, our work focuses on general mechanisms of metabolic control. Methodologically, we integrate bioenergetics, metabolomics and stable isotope tracing, and live cell imaging to characterize mitochondrial metabolism in response to physiologically relevant stimuli and drug candidates.
Mitochondrial remodeling during macrophage activation
Profound metabolic changes occur hand-in-hand with activation of macrophages, innate immune cells responsible for a remarkable breadth of processes such as pathogen elimination, antigen presentation, debris clearance, and wound healing. Our work seeks to define precisely how mitochondrial metabolism directly affects innate immunity, and exactly which features of macrophage activation are controlled by this metabolic reprogramming.
How metabolic flexibility can control cell physiology
It is now clear that altering flux through specific metabolic pathways, without changing bioenergetic rates per se, can have substantial impacts on physiological and disease processes as varied as oncogenesis, heart failure, immune cell activation, and neuronal excitability. Our work seeks to understand how shifting the nutrient preference away from oxidation of glucose and towards that of amino acids, fatty acids, and ketone bodies can adjust cell and tissue physiology in the context of neurodegeneration and heart failure.
Assay development and experimental guides
Hand-in-hand with academic work, we also develop new and accessible methods for energy metabolism research. Additionally, we aim to help others design experiments and interpret data with methods-focused roadmaps and perspectives.
