Candidate: The goal of the principal investigator is to become an independently funded surgical scientist who translates basic immunology into solutions for the most challenging problems in severe burns and trauma. The principal investigator has a strong preliminary record, having completed a N1H-NRSA trauma training fellowship and published a number of scientific manuscripts. The proposal, designed for long-term scientific success, outlines a specific training plan that includes didactic work, technical workshops, direct laboratory supervision, ethics, and professional development in applied basic science research. Environment: UNC-CH has a strong academic tradition and a commitment to training clinician scientists. The school has a number of core facilities, including the Lineberger Cancer Center and the Program in Molecular Biology and Biotechnology specifically designed to support the development of clinician scientists. Dr. Jeffrey A. Frelinger, PhD, Chair, Department of Microbiology and Immunology, the mentor for this proposal, has a long track record of scientific success and is committed specifically to the scientific development of the principal investigator. All required laboratory equipment, resources, expertise, and office space necessary for successful completion of this proposal will be available to the principal investigator. The Department of Surgery is absolutely committed to the scientific development of the principal investigator and his firm commitment to spend 75% of his time on this proposal. Research: The goal of this proposal is to determine the CD8+ T cell response to burn injury. CD8+ T cells, increasingly recognized as an important regulator of the immune response, have a poorly understood response to burn injury. Preliminary data reveals that while the CTL alloresponse to burn injury is impaired, the phenotype of activated CD8+ T cells suggests an exaggerated proinflammatory response. The hypothesis of this proposal is that the CD8+ T cell response to burn injury is pleiotropic and the mechanism for this response is altered CD8+ T cell activation. The principal investigator will use a variety of advanced cellular immunologic techniques to determine the phenotype and function of CD8+ T cells after burn injury. In addition, the mechanisms of CD8+ T cell activation will be investigated, specifically how the host environment and the cytokine environment influence the CD8+ T cell response to burn injury.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Clinical Investigator Award (CIA) (K08)
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Study Section
Surgery, Anesthesiology and Trauma Study Section (SAT)
Program Officer
Somers, Scott D
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University of North Carolina Chapel Hill
Schools of Medicine
Chapel Hill
United States
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Cairns, Bruce A; Barnes, Carie M; Mlot, Stefan et al. (2008) Toll-like receptor 2 and 4 ligation results in complex altered cytokine profiles early and late after burn injury. J Trauma 64:1069-77;discussion 1077-8
Maile, Robert; Pop, Shannon M; Tisch, Roland et al. (2006) Low-avidity CD8lo T cells induced by incomplete antigen stimulation in vivo regulate naive higher avidity CD8hi T cell responses to the same antigen. Eur J Immunol 36:397-410
Buchanan, Ian B; Maile, Robert; Frelinger, Jeffrey A et al. (2006) The effect of burn injury on CD8+ and CD4+ T cells in an irradiation model of homeostatic proliferation. J Trauma 61:1062-8
Maile, Robert; Barnes, Carie M; Nielsen, Alma I et al. (2006) Lymphopenia-induced homeostatic proliferation of CD8+ T cells is a mechanism for effective allogeneic skin graft rejection following burn injury. J Immunol 176:6717-26
Fair, Jeffrey H; Cairns, Bruce A; Lapaglia, Michael A et al. (2005) Correction of factor IX deficiency in mice by embryonic stem cells differentiated in vitro. Proc Natl Acad Sci U S A 102:2958-63