Timothy Wai

The research focus of the lab is to understand the complex interplay of mitochondrial dynamics and metabolism in health and disease. Mitochondria are essential organelles whose morphology varies tremendously across cell types and tissues. Balanced fusion and fission events shape mitochondria to meet metabolic demands and to ensure removal of damaged organelles. The dynamism of mitochondria is highlighted by the dramatic changes in morphology they undergo in response to metabolic inputs. Mitochondrial fragmentation occurs in response to nutrient excess and cellular dysfunction and has been observed in cardiovascular and neuromuscular disorders, cancer, and obesity. The morphology of mitochondria is inextricably linked to its many essential functions in the cell and we are interested in understanding the relationship between mitochondrial shape changes and metabolism in the context of acquired and inborn human diseases Objectives. Mitochondria are essential organelles whose morphology varies tremendously across cell types. The physiological relevance of mitochondrial morphology and the mechanisms that regulate mitochondrial dynamics in vivo are poorly understood. We seek to: • Identify the metabolic signals that balance mitochondrial fusion and fission • Define the molecular mechanisms of stress-induced fission • Design strategies aimed at re-balancing mitochondrial dynamics in vivo • Translate our experimental findings to acquired and inborn human diseases Strategy. Our research strategy builds upon frontier science in the areas of cell biology and biochemistry of mitochondria. We apply this knowledge to preclinical animal models and cellular models derived from patient biopsies to address fundamental translational knowledge gaps in rare genetic diseases of metabolism as well as common acquired age-associated diseases which include cardiovascular disease, cancer, and neurodegeneration.