Clair L. Crewe, PhD

Assistant Professor, Cell Biology and Physiology | Endocrinology, Metabolism and Lipid Research

Research Interest

Metabolic Regulation

Category(ies) of Research


Descriptor of Research

My research has focused on understanding extracellular vesicle (EV)-mediated signaling during homeostatic and pathologic metabolic regulation. Crosstalk between adipocytes and cells within the adipose tissue (AT) microenvironment directs healthy tissue expansion in response to overnutrition. In contrast, the inability to coordinate these inter-cellular signals during nutrient stress results in AT hypoxia, inflammation, and fibrosis, all of which contribute to metabolic disturbances in obesity and type 2 diabetes. My work has uncovered the existence of an expansive EV-mediated signaling network within the AT proper, and from the adipose tissue to other organs. This mainly adipocyte-derived EV population consists of exosome-like vesicles that carry proteins, RNAs and lipid species that can modulate a variety of signaling pathways in recipient cells. For example, we have recently demonstrated that adipocytes undergoing mitochondria-specific energetic stress, as in the obese condition, release small EVs (sEVs) containing mitochondrial particles that are respiration-competent but oxidatively damaged. These EV-enclosed mitochondria enter circulation and incorporate into the cardiomyocyte mitochondrial network resulting in transient mitochondrial dysfunction and free radical production. This is not a pathological process but, instead, results in a robust adaptation of the heart to combat this adipocyte sEV-imposed stress. Through this adaptive mechanism a single injection of sEVs from palmitate-stressed adipocytes limits cardiac ischemia/reperfusion injury, a common pathology in human obesity. The focus of my future
research is to determine how the various cargo of adipocyte EVs, like mitochondria, signal between cells within the adipose tissue and between adipose tissue and distal organs to modulate metabolism in obesity.