The Pathology Core has a unique team of investigators with the professional expertise to assist with the design and implementation of the unique vaccine strategies proposed. The Core Director, Dr. Altman, is a veterinary pathologist and laboratory animal veterinarian. He will coordinate tissue collection, presevation, sample preparation, and distribution. Additional, he will assist in the intrepatation of tissue changes and biomarkers. The Co-Director, Dr. Nadji, is a surgical pathologist with expertise in diagnostic and predictive biomarkers. He has developed unique procedures which will be extremely important in identifing the molecular and cellular mechanisms involved in the immune responses. The techniques proposed including immunohistochemistry and in situ hybridization are highly sensitive in identification of cellular changes. The procedures utilized will preserve macromolecules in tissue traditionally achieved by immediate freezing. The Research lnvestigator, Dr. Datar, is the Co-Director of the UM Biomedical Nanotechnology Institute and an experienced molecular biologist with many years of experience in gene expression analysis of fresh and archival tissues. He will lead the Laser Capture Microdissection procedues which are critical to the research projects in this proposal. Lay Summary: This project is targeted to use two novel vaccine strategies in a Rhesus monkey model of SIV infection to understand the molecular and cellular mechanisms that provide protection against this disease. State-of-the art-techniques and procedures will be utilized to characterize changes at critical time points after infection. The information obtained will help to develop an effective HIV vaccine for humans.
It is extremely important the new vaccine strategies be developed to implement effective vaccines for HIV. SIV studies in rhesus monkey are an excellent approach to understanding the cellular and molecular mechanisms in developing these vaccines. The novel approaches outlined in this proposal will provide valuable information in developing a vaccine for HIV.
|McCormack, Ryan M; Lyapichev, Kirill; Olsson, Melissa L et al. (2015) Enteric pathogens deploy cell cycle inhibiting factors to block the bactericidal activity of Perforin-2. Elife 4:|
|McCormack, Ryan M; de Armas, Lesley R; Shiratsuchi, Motoaki et al. (2015) Perforin-2 is essential for intracellular defense of parenchymal cells and phagocytes against pathogenic bacteria. Elife 4:|
|Hatfield, Stephen M; Kjaergaard, Jorgen; Lukashev, Dmitriy et al. (2015) Immunological mechanisms of the antitumor effects of supplemental oxygenation. Sci Transl Med 7:277ra30|
|Selinger, Christian; Strbo, Natasa; Gonzalez, Louis et al. (2014) Multiple low-dose challenges in a rhesus macaque AIDS vaccine trial result in an evolving host response that affects protective outcome. Clin Vaccine Immunol 21:1650-60|
|Newman, Robert G; Dee, Michael J; Malek, Thomas R et al. (2014) Heat shock protein vaccination and directed IL-2 therapy amplify tumor immunity rapidly following bone marrow transplantation in mice. Blood 123:3045-55|
|Gonzalez, Louis; Strbo, Natasa; Podack, Eckhard R (2013) Humanized mice: novel model for studying mechanisms of human immune-based therapies. Immunol Res 57:326-34|
|Fields, K A; McCormack, R; de Armas, L R et al. (2013) Perforin-2 restricts growth of Chlamydia trachomatis in macrophages. Infect Immun 81:3045-54|
|Schreiber, Taylor H; Wolf, Dietlinde; Bodero, Maria et al. (2012) T cell costimulation by TNFR superfamily (TNFRSF)4 and TNFRSF25 in the context of vaccination. J Immunol 189:3311-8|
|Xiao, Yanping; Motomura, Seiichi; Deyev, Vadim et al. (2011) TNF superfamily member 13, APRIL, inhibits allergic lung inflammation. Eur J Immunol 41:164-71|