Our laboratory investigates the regulation of anti-viral immune responses. A major focus of the laboratory is cytotoxic CD8+ T cells, which can kill other cells and play an important role in controlling viral infections. The signaling requirements for the generation of effector and memory cytotoxic CD8+ T cells are being investigated. Strategies to block infection and inflammation from viruses are also being investigated.
Human immunodeficiency virus (HIV)-related studies: A number of approaches are being taken in the lab to understand and characterize the function of HIV-specific CD8+ T cells in patients with HIV infection and to elucidate their costimulation and cytokine requirements for maximal functionality. We are investigating the mechanisms that contribute to the functional impairment of HIV-specific CD8+ T cells. What drives chronic immune activation, an important factor for disease progression in HIV infection, is also a focus of our research efforts.
The preclinical development of novel microbicides is being carried out in the laboratory. Novel dual action microbicides that prevent HIV infection while reducing inflammation are being investigated. These microbicides are potent inhibitors of HIV virus but also inhibit Type I IFN production while exhibiting no toxicity. In vitro studies are examining the efficacy of these compounds, their stability and their ability to withstand pH transition.
The cytokine network of acute SIV infection is being investigated. Studies with SIV-infected non-human primates are investigating the mechanism by which cytokines that increase during acute SIV infection can control host-virus equilibrium and disease progression in animals. These studies have established a novel model by which viral set point can be altered, and this may allow us to further investigate what controls viral set point in animals.
CD8+ T cell Immunity: Using a model of Influenza type A virus and Listeria monocytogenes infection in mice, we are investigating the in vivo regulation and costimulation requirements of cytotoxic anti-viral CD8+ T cell responses. The roles of cytokines and costimulation molecules in the generation and regulation of primary, secondary, and memory anti-viral CD8+ T cell responses are being examined. The role of microRNA such as miR-155 in the development of CD8+ T cell responses is being examined. Finally, how dendritic cells initiate and regulate cytotoxic CD8+ T cell responses is also being explored.
Influenza type A virus studies
Pathogenesis: What pathogenic mechanisms are at action during influenza virus infection is poorly understood. We are investigating the mechanisms that underlie the morbidity associated with influenza virus infection and are dissecting the triggers that lead to inflammation and disease. Signaling molecules such as PI3 kinase isoforms are being investigated for their role in pathogenesis. An understanding of the pathogenic process may allow us to develop novel treatments for pandemic and seasonal influenza virus infections.
Vaccine development: Vaccines that elicit CD8+ T cell responses against influenza virus have the potential to act as "universal" vaccines that provide broad protection against multiple strains of influenza virus. For this purpose we are developing novel vaccine approaches that potently stimulate a CD8+ T cell response against influenza virus and may reduce the morbidity and mortality of potential pandemic and seasonal strains of influenza virus infection.
Selected Publications: (See all Peter Katsikis's publications in PubMed.)
"A new mechanism of gene regulation mediated by noncoding RNA"
Turner M, and PD Katsikis
J. Immunol., 189: 3-4, 2012.
"The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point?"
Katsikis PD, Mueller YM and Villinger F.
PLoS Pathogens, e1002055, 2011.
"Dendritic cells and CD28 costimulation are required to sustain virus-specific CD8+ T cell responses during the effector phase in vivo"
Dolfi DV, Duttagupta PA, Boesteanu AC, Mueller YM, Oliai C, Borowski, AB and Katsikis PD
Journal of Immunology, 186: 4599–4608, 2011.
"Biopolymer encapsulated live influenza virus as a universal CD8+ T cell vaccine against influenza virus"
Boesteanu AC, Babu NS, Wheatley MA, Papazoglou ES and Katsikis PD
Vaccine, 29: 314–322, 2010.
"Phosphorothioate 2′ deoxyribose oligomers as microbicides that inhibit human immunodeficiency virus type 1 (HIV-1) infection and block Toll-like receptor (TLR) 7/9-triggering by HIV-1"
Fraietta JA, Mueller YM, Do H. D, Holmes VM, Howett MK, Lewis MG, Boesteanu AC, Alkan SS and Katsikis PD
Antimicrob. Agents Chemother., 54: 4064-4073, 2010.
"CD8+ cell depletion of SHIV89.6P-infected macaques induces CD4+ T cell proliferation that contributes to increased viral loads"
Mueller YM, Do HD, Boyer JD, Kader M, Mattapallil JJ, Lewis MG, Weiner DB, and Katsikis PD
Journal of Immunology, 183: 5006-5012, 2009
"Memory T cells require CD28 costimulation to remember"
Boesteanu AC and Katsikis PD
Seminars in Journal of Immunology, 21:69–77, 2009
"IL-15 treatment during acute SIV infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses"
Mueller YM, Duc DH, Altork SR, Artlett CM, Gracely EJ, Katsetos CD, Legido A, Villinger F, Altman JD, Brown CR, Lewis MG, and Katsikis PD
Journal of Immunology 180: 350-360, 2008.
"Memory CD8+ T cells require CD28 costimulation"
Borowski AB, Boesteanu AC, Mueller YM, Carafides C, Altman JD, Jennings S. R, and P.D. Katsikis
Journal of Immunology 179: 6494-6503, 2007.
"Probing the 'labyrinth' linking the innate and adaptive immune systems"
Katsikis PD, Schoenberger SP, and B Pulendran.
Nature Immunology 8: 899-901, 2007.
"Early Establishment and Antigen Dependence of Simian Immunodeficiency Virus-Specific CD8+ T-Cell Defects"
Mueller YM, Petrovas C, Do DH, Altork SR, Fischer-Smith T, Rappaport J, Altman JD, Lewis M. G, and P.D. Katsikis
Journal of Virology, 81: 10861-10868, 2007.
"Increased mitochondrial mass characterizes the survival defect of HIV-specific CD8+ T cells"
Petrovas C, Mueller YM, Dimitriou ID, Altork SR, Banerjee A, Sklar P, Mounzer KC, Altman JD, and Katsikis PD
Blood, 109: 2505-2513, 2007.
"IL-15 increases effector memory CD8+ T cells and NK cells in SIV-infected macaques"
Mueller Y. M, Petrovas C, Bojczuk P, Dimitriou ID, Beer B, Silvera P, Villinger F, Cairns JS, Gracely E, Lewis MG, and Katsikis PD
Journal of Virology,79: 4877-4885, 2005.
"IL-15 enhances survival and function of HIV-specific CD8+ T cells"
Mueller YM, Bojczuk P, Witek J, Altman JD, and Katsikis PD
Blood, 101: 1024-1029, 2003.
"In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses"
Halstead SE, Mueller YM, Altman JD, and Katsikis PD
Nature Immunology, 3: 536-541, 2002.