Education & Training
- Medical School – University of Pittsburgh – MD
- Residency – University of Pittsburgh – General Surgery
- Fellowship – University of Pittsburgh – Surgical Critical Care
- Post-Doctoral – University of Pittsburgh – Inflammation and Innate Immunity
NIH Grants: R35
I am a surgeon-scientist with a clinical practice consisting of trauma, emergency general surgery, and surgical critical care as well as a translational research interest in coagulopathy in the setting of injury. My basic science laboratory focuses on understanding the mechanisms of hemostasis and coagulation following trauma and hemorrhagic shock with a specific interest in the impact of sterile inflammation on platelet function. 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 the expression of the innate immune receptor, toll-like receptor 4 (TLR4) and the endogenous danger signaling molecule, high mobility group box 1 protein (HMGB1) on platelets, with deranged signaling leading to microvascular thrombosis and organ injury. We are testing multiple drug targets for regulating innate immune signaling and attenuating platelet dysfunction following trauma. The lab has multiple collaborations studying immunothrombosis in various disease states including cancer and sickle cell anemia. We also have an interest in targeted platelet therapy and have begun to devise novel platelet-specific nanotechnology for drug delivery. We have a multi-disciplinary collaboration combining international experts in platelet biology, coagulopathy, cellular imaging, nanotechnology, biomedical engineering, and innate immune signaling.
- Vogel S, Bodenstein R, Chen Q, Feil S, Feil R, Rheinlaender J, Schäffer TE, Bohn E, Frick JS, Borst O, Münzer P, Walker B, Markel J, Csanyi G, Pagano PJ, Loughran P, Jessup ME, Watkins SC, Bullock GC, Sperry JL, Zuckerbraun BS, Billiar TR, Lotze MT, Gawaz M, Neal MD. Platelet derived HMGB1 is a critical mediator of thrombosis. Journal of Clinical Investigation. 2015 Dec 1;125(12):4638-54
- Dyer MR, Chen Q, Haldeman S, Yazdani H, Hoffman R, Loughran P, Tsung A, Zuckerbraun BS, Simmons RL, Neal MD. Deep vein thrombosis in mice is regulated by platelet HMGB1 through release of neutrophil-extracellular traps and DNA. Sci Reports. 2018 Feb 1;8(1):2068.
- Dyer MR, Hickman D, Luc N, Haldeman S, Loughran P, Pawlwoski C, Gupta AS, Neal MD. Intravenous administration of synthetic platelets (SynthoPlate) in a mouse liver injury model of uncontrolled hemorrhage improves hemostasis. J Trauma Acute Care Surg. 2018 Jun;84(6):917-923.
- Zhou H, Deng M, Liu Y, Yang C, Hoffman R, Zhou J, Loughran PA, Liao H, Scott MJ, Neal MD*, Billiar TR*. Platelet HMGB1 is Required for Efficient Bacterial Clearance in Intra-abdominal Bacterial Sepsis. Blood Adv 2018 Mar 27;2(6):638-648 *co-senior and corresponding author
- Etchill EW, Rosengart MRR, McDaniel LM, Myers SP, Raval JS, Triulzi DJ, Peitzman AB, Sperry JL, Neal MD. Should all massive transfusion patients be treated equally? An analysis of massive transfusion ratios in the non-trauma setting. Crit Care Med. 2017 Aug;45(8):1311-1316.
- Sperry JL, Guyette FX, Brown JB, Yazer MH, Triulzi DJ, Early-Young BJ, Adams PW, Daley BJ, Miller RS, Harbrecht BG, Claridge JA, Phelan HA, Witham WR, Putnam AT, Duane LM, Alarcon LH, Callaway CW, Zuckerbraun BS, Neal MD, Rosengart MR, Forsythe RM, Billiar TR, Yealy DM, Peitzman AB, Zenati MS, for the PAMPer study group. Prehospital Air Medical Plasma Following Trauma and Hemorrhagic Shock: Results of the PAMPer Cluster Randomized Trial. New England Journal of Medicine. 2018 Jul 26;379(4):315-326