Diversity Supplement to R35 - Mechanistic Elucidation and Targeted Therapy of Organ Injury and Inflammation following Trauma

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Project Summary/Abstract from the Parent Grant (R35 to Matthew Neal): Multiple organ dysfunction syndrome (MODS) is a leading cause of death after severe trauma, which is a leading cause of mortality worldwide. MODS is thought to be a consequence of a vicious cascade of excessive inflammation and coagulation abnormalities but remains incompletely understood. The overarching goal of our research is to understand how trauma leads to organ injury through inflammation and clotting of blood vessels, or immunothrombosis. Our research focus is the central role of platelet function in driving immunothrombosis after trauma. We propose to tackle the following key knowledge gaps in the field: 1) Understand the cellular mechanisms leading to micro-thrombotic organ injury in survivors after trauma 2) Unravel the immune and inflammatory consequences of modern trauma resuscitation 3) Design targeted interventions for post-traumatic organ injury and thrombosis Project Summary/Abstract for the Diversity Research Supplement: The career development focus of this diversity research supplement is to foster the continuous effort of inclusion of faculty from under represented groups by increasing diversity in the Department of Surgery at the University of Pittsburgh and the University of Pittsburgh Medical Center. Dr. Mota Alvidrez as a Hispanic junior faculty member is a perfect candidate for this supplement as a very promising physician scientist that brings his expertise to this research team. His inclusion as a diverse individual will also focus in developing further his expertise in platelet biology/function, immunothrombosis and endothelial damage using state of the art microfluidic system assessment. Inclusion of Dr. Mota Alvidrez as faculty in our department aims to foster the success of the project but also by increasing diversity in faculty appointments particularly by the addition of highly determined and strong-driven individuals as Dr. Mota Alvidrez. The research supplement aims to develop Dr. Mota Alvidrez independent research program by growing the mechanisms outlined in the parent grant with his own independent research development plan. He has an amazing mentoring team with an outlined 5-year plan that will allow ample time for faculty development, data analysis, mentoring and grantsmanship for him to secure independent funding to build his research program and laboratory. The proposed research supplement for Dr. Mota Alvidrez will focus on expanding the scope of the key challenges in the parent grant outlined above. The scientific scope will add novel hypothesis-driven experimental studies from the exciting preliminary plan from Dr. Mota Alvidrez to promote the development of his independent research program focusing in immunothrombosis. Dr. Mota Alvidrez research will fill knowledge gaps in the field of immunothrombosis in trauma while advancing the needle in post-injury care. He proposes to study deeper into the endothelial damage post trauma by evidencing platelet receptor shedding, particularly GPIb, leading to thrombocytopenia. His work will evaluate how dysfunctional platelets leads to platelet sequestration and microthrombi formation by evaluating the A2 domain in von Willbrand factor as a key mediator of multimer formation in this process.