Aaron Petrey Lab - Research | Pathology | University of Utah Health

Our Research

Q: How do hyaluronan (HA) cables mediate inflammatory pathologies?

HA is an abundant molecule on the surface of cells that acts as an interface with the external environment. During inflammation, HA becomes increased and modified into cable-like structures that play a central role in mediating immune cell recruitment in several inflammatory disease states. Current work is determining the molecular mechanisms by which HA cables are regulated in endothelial, epithelial, and bone marrow mesenchymal cells. We are also investigating how HA-receptors present on immune cells and platelets become activated upon recognition of this novel cell-surface HA complex.

Q: How do platelet HA receptors mediate thromboinflammation?

In patients with Inflammatory Bowel Disease (IBD), HA cables present on the surface of microvascular endothelial cells act to recruit platelets and immune cells to sites of tissue damage. Platelets from IBD patients are deficient in a key enzyme required to degrade HA (HYAL-2), leading to impaired regulation of vascular HA and formation of microthrombi. Current work is determining how HA receptors regulate platelet function and mediate platelet aggregation and coagulation. This work will define how platelets recognize HA and lead to the development of new therapies useful for treating inflammation and thrombosis.

Q: How do HA-fragments contribute to humoral responses?

In response to severe inflammation seen in critical illnesses such as sepsis and COVID-19, HA becomes released from vascular surfaces and circulates as small pro-inflammatory fragments. These HA fragments are increased up to 30-times the normal levels found in healthy individuals and can function as damage associated molecular patterns capable of stimulating gene expression and altering cell behavior. Current work is determining how HA fragments alter signaling pathways in immune and endothelial cells during disease.