Molecular Physiology Lab
The Molecular Physiology Laboratory studies how sub-cellular pathways and molecular functions in tissues influence whole-body metabolism, and vice-versa. The group leverages a wide array of cell, molecular, and physiology techniques to address questions relevant to metabolic health and to diseases such as type 2 diabetes and obesity. Working in a multidisciplinary, collaborative environment, the team applies tools such as metabolomics, microbiome analysis, and animal models to gather a broader picture of physiological function. Clinical studies include controlled feeding experiments, fitness intervention and monitoring whole-body and molecular physiology during acute exercise and fatigue.
By understanding the fundamental biology and regulatory systems that define metabolic health, the Lab aims to provide the evidence base needed to craft effective strategies to thwart disease and improve health and development of children and adults.
Exercise, Metabolic Health, and Gut Microbiome
Regular physical activity is clearly associated with reduced disease burden and improved overall health and development. Yet, the specific molecular factors involved in this association remains to be fully elaborated. By studying blood and muscle interstitial fluid metabolomics at rest and during exercise, under a variety of conditions in rodents and humans, the Lab has discovered that (a) improved metabolic health and fitness are coincident with changes in the circulating concentrations of gut bacteria-derived metabolites (xenometabolites), presumably via host-to-bacteria signals that regulate microbial ecology; (b) despite intervention that improves fitness, body weight and insulin sensitivity, exercise-associated blood markers of incomplete fat combustion (medium-chain acylcarnitines) remain equivalent—this indicates that regardless of metabolic health status, inefficiencies in fat oxidation are inherent to exercise; (c) muscle interstitial fluid metabolomics revealed hundreds of metabolites sensitive to exercise in rats and humans, many of which are detected in the fluid but not the blood. The findings point to several potential muscle exertion/fatigue signaling molecules and revealed global metabolism shifts in muscle during exercise.
Muscle Lipid Trafficking
The specific means by which fatty acids and their derivatives are trafficked and sequestered in muscle are not fully known. The fate of lipids in myocytes has profound importance to understanding fundamental principles around fat oxidation and lipotoxicity; the latter is implicated in driving insulin resistance and muscle dysfunction. The Molecular Physiology team has characterized fatty acid and acylcarnitine binding to the oxygen carrier myoglobin, a novel mechanism by which oxidative metabolism, fat combustion, and lipid accumulation could be linked and regulated. Current studies are examining how manipulation of the myoglobin system impacts muscle health and function.