This K-23 award will provide an opportunity for Dr. Watkins to develop as an independent scientific investigator in the field of clinical and translational research, investigating the risk factors, and potentially causal factors, which explain the relationship between blood transfusion and trauma-associated acute lung injury (ALI). This will be accomplished through an integrated curriculum consisting of coursework in epidemiology and biostatistics;intensive mentoring by local experts in the complications of severe trauma, ALI biology, and transfusion medicine;and practical experience in designing, conducting, and interpreting a clinical research project. Dr. Watkins will use this award to become an independently funded clinical investigator with skills in advanced multivariate statistical methods and in the design of clinical and transitional studies which include planned biologic sampling strategies necessary for biomarker discovery and future gene expression studies. Moreover, he will gain an ability to design and implement clinically focused projects which translate basic science advances into clinical practice, and also translate observed clinical associations into new basic science studies focusing on organ injury mechanisms. This will lead to a successful independent research career focused on understanding the clinical and biologic role of blood transfusion in the development of trauma-associated ALI and other trauma-related organ dysfunction. The primary scientific goal of this proposal is to determine the role of blood product storage time and cell-derived microparticles in the development of trauma-associated ALI. To achieve this goal Dr. Watkins will: I.) establish the relationship between the storage time of transfused red blood cells and the development of trauma-associated ALI in severely injured patients requiring transfusion, II.) compare the quantity of cellderived microparticles within donor blood that is transfused to patients who subsequently develop, versus do not develop, trauma-associated ALI, and III.) obtain blood samples from a well-defined, severely injured trauma patient phenotype and: A.) use these samples to determine the associations between circulating cellderived microparticles, transfusion, and trauma-associated ALI, and B.) establish an RNA repository from circulating leukocytes which will be archived for future studies aimed at identifying gene expression patterns associated with blood transfusion and with trauma-associated ALI.
This project has important implications for those with severe trauma. The identification of potentially causal and modifiable factors important to the development of ALI could translate into novel biomarkers or new blood product storage, processing, or transfusion guidelines. The goal of the microparticle studies is to reveal novel mechanisms of disease, opening new avenues for basic study. Finally, the identification of modifiable factors showing promise in preventing trauma-associated ALI could be tested as interventions in future randomized clinical trials.
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