Role of RAGE in Transfusion Mediated Acute Lung Injury

University Of Pennsylvania, Philadelphia PA

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Abstract

DESCRIPTION (provided by applicant): This proposal describes a 5 year training program for a career in investigative medicine in Pulmonary Diseases with the long term goal of establishing a research program within the field of acute lung injury. The applicant has finished a fellowship in Pulmonary, Allergy and Critical Care Medicine at the University of Pittsburgh and is currently completing a research fellowship at the University of Pennsylvania. She is currently conducting research in transfusion-mediated acute lung injury, a common problem in the critically ill population. The research focus of this proposal is to elucidate some of the mechanisms by which stored erythrocytes induce lung injury during systemic inflammatory states. The central hypothesis of the proposal is that transfused RBC's directly activate pulmonary endothelial cells and neutrophils through the receptor for advanced glycation endproducts (RAGE) causing lung injury. In Specific Aim 1, the role of RAGE in endothelial cell activation induced by banked human RBCs will be defined. In Specific Aim 2, the effects of stored RBCs on neutrophil function in vitro and in vivo will be studied. In Specific Aim 3, the mechanisms by which stored RBCs induce lung injury during endotoxemia will be explored using mouse models. The training component of this proposal includes formal coursework, participation in a rich environment of post-doctoral lectures and seminars in lung diseases, acquisition of advanced laboratory techniques, and individual mentoring. This project will take place under the supervision of Dr. Steven Albelda who is the Director of Lung Research and Vice-chief of the Division of Pulmonary, Allergy and Critical Care Medicine at Penn. He has mentored over 60 trainees. In addition, an advisory committee of distinguished scientists will provide experimental assistance, intellectual guidance, and career advice throughout the duration of this award.