Endotheliopathy and Lung Injury after Trauma
Trauma-induced endothelial cell damage (“endotheliopathy”) leading to organ failure is a major cause of morbidity and mortality after injury. The endothelial glycocalyx is a layer of proteoglycans and glycosaminoglycans that serves as a key regulator of endothelial permeability and barrier function. Damage to the glycocalyx occurs in response to the proinflammatory milieu of injury, which is a key factor of trauma-induced endotheliopathy. In trauma patients, circulating levels of shed glycocalyx constituents correlate with injury severity and mortality. Preclinical studies have demonstrated that glycocalyx damage correlates with lung injury after trauma, but the mechanisms responsible for glycocalyx shedding are poorly understood. Our goal is to elucidate mediators of trauma-related endotheliopathy that regulate glycocalyx damage.
Glycocalyx-Mediated Mechanotransduction Signaling during Hemorrhage and Resuscitation
The endothelial glycocalyx functions as a mechanosensor and transducer that regulates endothelial cell behavior in response to changes in hemodynamic environment. During traumatic hemorrhage, the glycocalyx is damaged, which we believe leads to impaired mechanosignaling and a dysregulated endothelial response to subsequent changes in vascular forces caused by fluid resuscitation. Our goal is to understand the role of glycocalyx-mediated mechanosignaling in regulating endothelial barrier function during hemorrhage and resuscitation in order to develop targeted resuscitative therapies that may prevent endotheliopathy and organ damage.
Lung Injury and Massive Transfusion with Stored Blood Products
Early management of hemorrhagic patients with red blood cell (RBC) transfusions is life-saving, although many preclinical and clinical studies indicate that massive transfusion for treatment of traumatic hemorrhagic shock increases the risk of secondary end-organ injury and infection. In particular, acute lung injury (ALI) leading to the acute respiratory distress syndrome (ARDS) is a common morbidity following severe trauma, and risk of ALI/ARDS after traumatic injury is estimated to increase by 6% with each unit of transfused blood. Our goal is to understand the causal relationship between traumatic hemorrhage, transfusion products and ALI in order to aid in the development of novel therapies to improve trauma outcomes.