Advancing Trauma and Critical Care Research
Traumatic injury is the leading cause of death among individuals aged 1-44, resulting in more potential life years lost than cancer, heart disease, and HIV combined. While early deaths from trauma often stem from massive hemorrhage or severe traumatic brain injury, delayed mortality is frequently due to complications such as organ failure, infection, and thromboembolic events. These complications arise from underlying dysfunctions in coagulation and inflammatory responses, processes that are intricately linked and drive preventable deaths in trauma-related cases and other critical illnesses.
Our lab, led by Dr. Christopher Barrett, is dedicated to investigating the molecular and cellular regulators of inflammation and coagulation in trauma, critical illness, and surgical diseases. We conduct both basic science and translational research to improve diagnostic and therapeutic strategies, bridging the gap between laboratory discoveries and clinical applications.
Our Research Focus
We explore multiple facets of trauma and critical care medicine, with ongoing projects that include:
- Trauma Bleeding Adjuncts: Studying the role of tranexamic acid as both a pro- and anti-inflammatory agent in traumatic injury through a plasminogen-activator dependent mechanism.
- Complement Activation in Injury: Investigating how the complement system is activated after trauma and hemodynamic shock, potentially leading to inflammatory organ failure.
- Organ Healing Mechanisms: Understanding the impact of bleeding adjunct therapies on liver regeneration, as the liver, the most commonly injured solid organ in trauma, relies on healing signals from proteins such as hepatocyte growth factor, which share evolutionary links with the fibrinolysis system.
- Neutrophil Protease Effects on Coagulation: Characterizing how inflammatory neutrophil proteases alter coagulation and fibrinolysis pathways by targeting key proteins such as plasminogen and fibrinogen, thereby influencing clot formation and breakdown.
- Fibrinolysis Resistance in Infections and Retained Blood: Investigating how infections and retained blood in the chest, often due to pneumonia or trauma, drive resistance to fibrinolysis therapy with tissue plasminogen activator and deoxyribonuclease, necessitating invasive surgical interventions.
Translational Research and Clinical Trials
We have a strong track record in developing novel therapeutic approaches and conducting clinical trials, including:
- The STARS Trial: A Phase IIa multicenter randomized trial evaluating systemic fibrinolysis with tissue plasminogen activator for treating severe respiratory failure (Barrett et al, CHEST 2022, PMID 34592318).
- The STAT Trial: A Phase II randomized trial assessing the efficacy of aspirin and rosuvastatin in reducing thromboembolic complications in critically ill trauma patients (Barrett et al, Blood Coagulation and Fibrinolysis 2023, PMID 37942744).
- Novel Diagnostic Assays: Development and validation of a rapid clinical diagnostic assay to detect fibrinolysis perturbations in severely injured patients (Barrett et al, J Trauma Acute Care Surg 2020, PMID 33230046).
- Ongoing Investigations: Several other diagnostic and therapeutic studies are currently in various stages of design and implementation, aiming to translate laboratory findings into clinical applications.
Through our integrative research approach, we are committed to improving patient outcomes in trauma and critical care by uncovering new biological mechanisms, identifying therapeutic targets, and advancing innovative treatments to the bedside.