Our research is focused on understanding extracellular vesicle (EV)-mediated signaling during homeostatic and pathologic metabolic regulation using adipose tissue as a model system. EVs are nanosized vesicles released from cells that carry proteins, RNAs and lipid species that can modulate a variety of signaling pathways in recipient cells. Adipose tissue is an ideal organ to study EV signaling as it is highly dynamic, requiring cross talk between multiple cell types to expand or contract in response to changes in nutrient availability. The health of the adipose tissue directly influences systemic metabolism. We study how EVs signaling within the tissue during physiological and pathological expansion and how they signal from adipose tissue to other organs. Understanding this form of inter-cellular communication promises to reveal fundamental nodes of metabolic regulation and thereby provide entirely new targets for pharmacological treatment of obesity, type 2 diabetes, and related comorbidities.
We are generating mouse lines to manipulate EV production in the cell-type and inducible way. These mice allow us to assess the effects of endogenous EVs on cellular and whole-body metabolism. We use state of the art instrumentation to characterize EVs from cell and tissue culture from both mice and humans.
We are committed to studying the translation of our findings to human disease. Through collaborations with physician scientists at WashU we can test our hypotheses in primary human cells.
We study how adipocyte stress-induced EV production and cargo selection is regulated. We are particularly interested in the decision of the cell to package pieces of damaged mitochondria into EVs (mitovesicles). Our previous work has found these adipocyte-derived mitovesicles are released from palmitate-stressed adipocytes and enter circulation. These traveling mitochondria are taken up by cardiomyocytes where alter redox signaling (Crewe et. al. Cell Metabolism. 2021).
Our work has uncovered the existence of EV-mediated signaling within the adipose tissue in vivo (Crewe et. al. Cell. 2018). We have determined that the adipocyte – endothelial EV transfer represents the most robust and exclusive EV signaling axis in adipose tissue. Our current work is focused on determining how these signaling events in the adipose tissue effect expansion and health of the tissue in the obese state.
Our studies, and others, have demonstrated that adipose-derived EVs can have a significant effect on systemic metabolism in obesity (Crewe et. al. Diabetes. 2022). We are interested in determining how adipocyte EVs influence comorbid disease progression in obesity, particularly cardiovascular disease.