This proposal is to provide the Principal Investigator, Dr. Timothy Schacker, a secure funding base to sustain a strong patient oriented research program that has, as an integral component, mentorship of junior faculty and fellows in all aspects of patient oriented research. Dr. Schacker is an excellent candidate for this award for several reasons. Throughout his career he has focused on pathogenesis and natural history based studies of Herpes Simplex Virus and HIV-1 that are exclusively patient oriented. He has both a strong publication and funding record for his research and has earned a reputation for successfully recruiting patients into complex and complicated protocols. In addition, Dr. Schacker is very active in the mentoring of young physicians in patient oriented research and clinical medicine. He is a founding faculty member of the Masters in Clinical Research program at the University of Minnesota, is actively involved with fellows and residents in the design and implementation of their own patient oriented research questions, and teaches in the year 1 and 2 Medical School curriculum. Recently he developed a unique forum for rapid response training of physicians in the recognition and treatment of infectious agents related to bioterrorism and is a Co-Investigator in a proposal to establish a regional center of excellence on this topic. Through this proposal Dr. Schacker will have sufficient resources to continue to build his patient oriented research program that examines the contribution of HIV-1 induced inflammation of lymphatic tissues to the immunopathogenesis of HIV-1 disease and, in addition, have protected time to provide more opportunities for mentoring junior faculty and fellows by integrating them into this program of research. The goals of the research proposal are to determine if analysis of architectural damage to the lymph node by fibrosis accurately predicts the degree of immunologic reconstitution with anti-HIV therapy and if this damage is reversible using novel therapeutic strategies.
|Estes, Jacob D; Reilly, Cavan; Trubey, Charles M et al. (2015) Antifibrotic therapy in simian immunodeficiency virus infection preserves CD4+ T-cell populations and improves immune reconstitution with antiretroviral therapy. J Infect Dis 211:744-54|
|Schacker, Timothy W; Bosch, Ronald J; Bennett, Kara et al. (2010) Measurement of naive CD4 cells reliably predicts potential for immune reconstitution in HIV. J Acquir Immune Defic Syndr 54:59-62|
|Brenchley, J M; Knox, K S; Asher, A I et al. (2008) High frequencies of polyfunctional HIV-specific T cells are associated with preservation of mucosal CD4 T cells in bronchoalveolar lavage. Mucosal Immunol 1:49-58|
|Brenchley, Jason M; Paiardini, Mirko; Knox, Kenneth S et al. (2008) Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. Blood 112:2826-35|
|Skarda, David E; Taylor, Jodie H; Chipman, Jeffrey G et al. (2007) Inguinal lymph node biopsy in patients infected with the human immunodeficiency virus is safe. Surg Infect (Larchmt) 8:173-8|
|Li, Qingsheng; Schacker, Timothy; Carlis, John et al. (2004) Functional genomic analysis of the response of HIV-1-infected lymphatic tissue to antiretroviral therapy. J Infect Dis 189:572-82|
|Brenchley, Jason M; Schacker, Timothy W; Ruff, Laura E et al. (2004) CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract. J Exp Med 200:749-59|