Dr. Alex St. John Receives Two Research Grants; UW RRF and NIH K08

Dr. Alexander St. John recently received funding for two different projects:

He received a 1-year, $40k UW Royalty Research Fund (RRF) Grant for his project titled "Understanding Microcirculatory Obstruction in Critical Illness."

Trauma is a major cause of morbidity and mortality. Trauma-induced coagulopathy (TIC) is a common and deadly complication of injury that leads to impaired blood clotting ability. TIC is associated with decreased and heterogeneous microvascular blood flow, which could account for organ dysfunction sometimes seen after trauma. The causes of TIC and microvascular blood flow derangement are unknown, but a likely candidate lies in the adhesive glycoprotein von Willebrand factor (VWF), which is released by cells lining the inner lumen of blood vessels in response to inadequate oxygen delivery, which occurs in severe trauma. In several other disease states, rampant VWF release and microclot formation lead to microvascular obstruction and bleeding abnormalities. This project will characterize the changes in microcirculation that occur after trauma and test the effects of two agents used to treat VWF accumulation in other disease states on the microcirculation in a rat model of polytrauma. The effects of those agents will clarify whether VWF plays a role in this disease process.

Dr. St. John also received a 5-year, $780k NIH K08 Grant for his project titled: "Dysregulation of Platelet-von Willebrand Factor Interaction in Trauma-Induced Coagulopathy."

The overall goal of this project is to improve the outcomes of injured patients with trauma-induced coagulopathy (TIC) by performing a detailed investigation of the mechanisms underlying this disorder. Trauma is a major cause of morbidity and mortality, and hemorrhage is the leading cause of potentially preventable death. TIC is a common complication of serious injury that impairs normal hemostasis and contributes to hemorrhage. Two prominent features of TIC are platelet dysfunction and derangement of microvascular blood flow. The causes of these abnormalities are not known, but preliminary data suggest several possible contributors, including the release of hyperadhesive von Willebrand factor (VWF) and actin, as well as alterations to platelet surface receptors. This project includes a set of experiments to elucidate the underlying causes of the platelet and microvascular changes of TIC. It aims to characterize the defects in VWF-platelet adhesion, the alterations of platelet surface receptors, and the effects of agents that modulate these pathways on clinical outcomes using a rat model of TIC. Ultimately, this project will fill critical knowledge gaps in the pathophysiology of TIC.

Congratulation, Dr. St. John!