My lab focuses on understanding the mechanisms of Hemostasis, Inflammation, and Thrombosis following Trauma and hemorrhagic shock with a translational focus in these areas as well as Transfusion medicine and Surgical outcomes (HIT3S Lab). Uncontrolled hemorrhage is the leading cause of preventable death in trauma, which accounts for nearly 10% of annual mortality worldwide. Over 25% of severely injured patients will present with impaired coagulation which increases morbidity and mortality. Although it is well known that trauma results in a profound inflammatory response driven by innate immune activation, the mechanisms of this acute coagulopathy of trauma are poorly understood. Our lab has recently discovered a potential link between sterile inflammation and impaired coagulation through expression of the innate immune receptor, toll-like receptor 4 (TLR4) and the endogenous danger signal, high mobility group box 1 (HMGB1), on platelets. We now seek to understand the regulation of innate immune signaling on platelets and are testing multiple drug targets to attenuate platelet dysfunction and prevent thrombotic complications following trauma. We have multiple ongoing studies investigating the mechanisms of venous thromboembolic events (VTE) as well as microvascular thrombosis. The lab is presently pursuing the role of platelet derived microparticles and exosomes in trauma and VTE.
We also have a dedicated interest in the development of a synthetic platelet for hemostasis after injury in collaboration with Anirban SenGupta, PhD, as well as the design of novel, platelet directed drug delivery systems. The lab collaborates closely with local and international platelet and coagulation experts. We are also co-lead investigators for the University of Pittsburgh effort in the NIH/DOD funded Trans-Agency Consortium for the study of Trauma Induced Coagulopathy (TACTIC) along with Dr. Brian Zuckerbraun. This multi-disciplinary collaboration combines international experts in platelet biology, coagulopathy, cellular imaging, and innate immune signaling to create a team well suited to this complex problem. The laboratory is supported by the National Institute for General Medical Sciences (NIGMS), the National Heart Lung and Blood Institute (NHLBI), BARDA, and the Vascular Medicine Institute at the University of Pittsburgh, as well as private industry.
Clinical research by the group focuses on surgical outcomes in trauma, transfusion medicine, and emergency general surgery. Examples on ongoing projects include the investigation of outcomes in non-trauma massive transfusion; determination of the significance of thrombocytopenia in the ICU, as well as the design of a scoring system to predict massive transfusion protocol activation in the setting of non-trauma massive hemorrhage. The lab actively participates in 2 Department of Defense (DoD) randomized clinical trials in trauma and transfusion as well as translational analysis of outcomes in TACTIC. Finally, we have an industry sponsored prospective observational trial to investigate the role of thromboelastography in the management of patients on novel direct oral anticoagulants (DOACs).
Clinical Research Group
NW632 UPMC Montefiore
Publications from the Neal Lab can be viewed through PubMed.