Understanding the Biological Response to Trauma

The biological response to trauma is a complex, dynamic process involving the immune system, coagulation pathways, platelets, and endothelial function. Our lab investigates how traumatic injury disrupts homeostasis and initiates a cascade of dysregulated inflammatory and thrombotic responses. Key work has explored immune cell activation, including macrophage polarization and mobilization, platelet dysfunction, and endothelial interactions that contribute to systemic effects beyond the site of injury. Our work in this area is highly translational and aims to bridge the gap between basic science and clinical application using trauma patient blood samples.

Research has demonstrated that trauma can provoke maladaptive hemostatic responses such as trauma-induced coagulopathy (TIC), which is associated with poor outcomes and increased mortality. Using in vivo models, clinical data, and specialized microfluidic devices, the lab has shown how altered platelet function, persistent von Willebrand factor multimer presence, and reduced ADAMTS13 activity exacerbate thromboinflammation. These insights help us understand clinical findings such as non-surgical bleeding, thrombotic microangiopathies, and end-organ damage following trauma.

Our work extends to central nervous system trauma, where the lab has studied platelet dysfunction in traumatic brain injury and the persistent inflammatory milieu it creates. The interplay between coagulation factors, cellular responses, and the injured endothelium remains a key research axis. These findings set the foundation for therapeutic strategies that modulate interactions between hemostasis and the immune system to improve outcomes in critically injured patients.

Understanding the Effect of Transfusion Processes on Blood Products

Modern transfusion practices are critical in trauma care, yet there is limited understanding of how storage, processing, and product manipulation affect blood component efficacy. The lab has studied the impact of various factors, such as cold storage, agitation, leukoreduction, and apheresis collection platforms, on platelet and plasma function. These studies have informed optimal handling techniques to preserve hemostatic potential while reducing complications associated with storage lesions and reduced metabolic integrity.

Work in this area includes evaluating key processing methods like pathogen reduction and the production of plasma supernatants from late-storage whole blood. These approaches aim to retain coagulation function and enhance shelf life while maintaining safety. The lab has also contributed to understanding how transfusion timing, dose, and product composition influence outcomes in patients with hemorrhagic shock, particularly through studies of low-titer group O whole blood use in both pediatric and adult trauma populations.

By applying both bench and clinical research methodologies—including viscoelastic assays and metabolomic profiling—the lab has helped define a more nuanced picture of what constitutes "high-quality" transfusion products. These findings support the broader goal of personalized transfusion strategies, where product selection is based not only on blood type compatibility but also on functional performance tailored to patient needs.

Creating New Blood Product Solutions

To address limitations of traditional transfusion therapy such as availability, shelf life, and immunogenicity, the lab is developing synthetic and bioengineered blood products. SynthoPlate is a leading example, designed to mimic platelet function through targeted nanoparticles that promote hemostasis at injury sites. Studies have shown SynthoPlate enhances clot formation and reduces bleeding in preclinical models, demonstrating its promise as a field-deployable hemostatic agent for military and civilian trauma settings.

This effort extends beyond SynthoPlate to the conceptual development of other bioinspired products. Research focuses on nanoparticle design, surface ligand optimization, and in vivo efficacy testing to ensure these agents replicate critical features of natural hemostasis. By bypassing reliance on donor-derived components, these products aim to reduce risk of transfusion reactions and allow for scalable, long-term storage—essential for austere or mass casualty environments.

The lab collaborates across disciplines including biological and biomedical engineering and materials science to optimize these technologies. Continued work in this area focuses on regulatory pathways, combination therapies (e.g., pairing synthetic platelets with antifibrinolytics), and real-world deployment models. These products hold the potential to revolutionize trauma care and fill gaps where traditional transfusion products fall short.

Mediators & Therapies for Thromboembolism

Thromboembolic disease is driven by the pathological intersection of thrombosis and inflammation. The lab’s work in this area focuses on uncovering the cellular and molecular mediators of clot formation and resolution, particularly in the setting of trauma, stroke, and critical illness. Key players such as platelets, neutrophils, and von Willebrand factor (VWF) are studied in detail to understand how they contribute to thrombus initiation, stabilization, and resolution. Advanced microfluidic models are leveraged to visualize these processes under physiologic flow, enabling real-time assessment of clot dynamics and cellular interactions.

A major translational effort centers on therapeutically targeting VWF, a critical mediator of arterial thrombosis. One study uses a microfluidic model of arterial occlusion to evaluate BB-031, an aptamer that selectively blocks the VWF-A1 domain. This inhibitor demonstrated superior thrombus clearance and reduced re-occlusive platelet deposition compared to conventional fibrinolytics like Alteplase and Tenecteplase, even when administered hours after occlusion. These findings highlight a paradigm shift in ischemic stroke treatment: from fibrinolysis to anti-adhesive therapies that prevent sustained occlusion and secondary thrombus growth.

The lab’s broader vision includes developing precision therapies that can modulate thromboinflammatory processes without impairing necessary hemostasis. This includes profiling patient-specific coagulation signatures using thrombin generation assays and viscoelastic testing, and identifying which individuals may benefit from agents like BB-031. By bridging mechanistic insights with therapeutic development, this work offers hope for safer and more effective treatment of thromboembolic disease—especially in settings where conventional anticoagulants and thrombolytics fall short.

Last Updated May 17, 2025