Peter D. Katsikis MD, PhD
Professor and Head of the Department of Immunology
Infection and Immunity Research Group (IIG)
+31-107044188 (Administrative Assistant)
Erasmus MC, University Medical Center
Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Infection and Immunity Research Group (IIG)
Our research group investigates immunity to pathogens and tumors. A major focus are cytotoxic CD8+ T lymphocytes (CTL), cells which can kill other cells and play an important role in controlling viral infections and cancer. An important goal of this research program is to elucidate the signaling and molecular requirements for the generation of successful effector and memory CTL and to understand why these cells fail in certain chronic infections and cancer.
To understand the molecular pathways that control of CTL responses, we study the signaling requirements and gene regulation networks that enable successful CTL responses. Through manipulation of gene expression and signal regulation pathways via genetically modified and conditional knock out animals, we aim to identify those mechanisms that contribute to successful clearance of viral infections. Current studies in our laboratory utilizing animal models that employ influenza virus and Listeria monocytogenes infections and mouse tumor models to characterizing the role of post-transcriptional gene expression regulation in CTL immunity. A rapid in vitro CTL exhaustion method has been developed to facilitate the testing of exhaustion reversal strategies.
Another central aim of our research is to understand why CTL fail in HIV infection and how to eliminate the latent HIV reservoir. Studies in our laboratory focus on understanding how CTL immunity develops and is regulated during acute HIV infection and what molecular and signaling pathways are affected in HIV-specific CTL during the chronic phase of HIV infection. The ultimate goal of this research is to discover novel means of restoring maximal functionality within these antiviral cells. To identify CTL enhancing targets, we are using retroviral vectors to screen for post-transcriptional gene expression regulators that can enhance CTL immunity in vitro and in vivo. These studies are being carried out in anti-viral CTL from both mice and HIV-infected patients. Strategies to reactivate HIV from latently infected cells and kill these cells via innate or adaptive immune responses are being explored together within a larger consortium of Cure researchers at Erasmus MC and beyond.
A third area of research is developing potent peptide-based vaccines for cancer. The goal of these studies are to develop personalized vaccines that efficiently target the neoantigens present in each patient’s tumors by combining novel neopeptide prediction algorithms and adjuvants with nanoparticles. These studies involve a large international and national collaboration of experts.
- Peter Katsikis M.D., Ph.D., Professor, Group leader
- Yvonne Mueller Ph.D., Assistant Professor
- Manzhi Zhao, PhD student
- Caoimhe Kiernan, Postdoctoral Scientist
- Melisa Castro Eiro, Postdoctoral Scientist
- Inge Brouwers-Haspels, Research Assistant
- Marjan van Meurs, Research Assistant
Hancock A, Stairiker CJ, Boesteanu AC, Monzón-Casanova E, Lukasiak S, Mueller YM, Stubbs A, Garcia-Sastre A, Turner M, Katsikis PD: Transcriptome analysis of infected and bystander type 2 alveolar epithelial cells during influenza A virus infection reveals in vivo Wnt pathway downregulation.
J. Virol. 92. pii: e01325-18, 2018
Palstra RJ, De Crignis E, Roling M, van Steveren T, Kan TW, van Ijcken W, Mueller YM, Katsikis PD, Mahmoudi T: Allele-specific long distance regulation of IL-32 confers susceptibility to HIV-1 infection.
Science Advances 4: e1701729, 2018
Stelekati E, Chen Z, Manne S, Kurachi M, Ali M, Lewy K, Cai Z, Hope JL, Fike A, Katsikis PD, Wherry EJ: Long-term persistence of exhausted CD8 T cells in chronic infection regulated by microRNA-155.
Cell Rep. 23:2142-2156, 2018
Gracias DT, Boesteanu AC, Fraietta JA, Hope JL, Carey AJ, Mueller YM, Kawalekar OU, Fike A, June CH, Katsikis PD: Phosphoinositide 3-Kinases p110δ isoform regulates CD8+ T cell responses during acute viral and intracellular bacterial infections.
J. Immunol. 196:1186-98, 2016
Carey AJ, Gracias DT, Thayer JL, Boesteanu AC, Kumova OK, Mueller YM, Hope JL, Fraietta JA, van Zessen DBH, Katsikis PD: Impaired CD8+ T cell responses to Influenza infection in neonatal mice are due to the immature TCR repertoire.
J. Immunol. 196:2602-13, 2016
Acute exposure to ZnO nanoparticles induces autophagic immune cell death.
Johnson BM, Fraietta JA, Gracias DT, Hope JL, Stairiker CJ, Patel PR, Mueller YM, McHugh MD, Jablonowski LJ, Wheatley MA, Katsikis PD.
Nanotoxicology. Nov 7:1-12, 2014
Bystander Chronic Infection Negatively Impacts Development of CD8 T Cell Memory.
Stelekati E, Shin H, Doering TA, Dolfi DV, Zeigler CG, Beiting D, Liboon J, Wolski D, Katsikis PD, Shen H, Roos DS, W. Haining WN, Lauer G, Wherry EJ.
Immunity 40:801-13, 2014
Abasic phosphorothioate oligomers inhibit HIV-1 reverse transcription and block virus transmission across polarized ectocervical organ cultures.
Fraietta JA, Mueller YM, Lozenski KL, Ratner D, Boesteanu AC, Hancock AS, Lackman-Smith C, Zentner IJ, Chaiken IM, Chung S, LeGrice SF, Snyder BA, Mankowski MK, Jones NM, Hope JL, Gupta P, Anderson SH, Wigdahl B, Katsikis PD.
Antimicrob Agents Chemother. 58:7056-71, 2014
Type I interferon upregulates Bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection.
Fraietta JA, Mueller YM, Yang G, Boesteanu AC, Gracias DT, Do DH, Hope JL, Kathuria N, McGettigan SE, Lewis MG, Giavedoni LD, Jacobson JM, Katsikis PD.
PLoS Pathog. 9:e1003658, 2013
The microRNA miR-155 controls CD8(+) T cell responses by regulating interferon signaling.
Gracias DT, Stelekati E, Hope JL, Boesteanu AC, Doering TA, Norton J, Mueller YM, Fraietta JA, Wherry EJ, Turner M, Katsikis PD.
Nat Immunol. 14:593-602, 2013.
A new mechanism of gene regulation mediated by noncoding RNA.
Turner M, Katsikis PD.
J Immunol. 189:3-4, 2012
The Inflammasome and Caspase-1 Involvement in Systemic Sclerosis Fibroblasts Mediates Fibrosis and Myofibroblast Differentiation.
Artlett CA, Sassi-Gaha S, Rieger JL, Boesteanu AC, Feghali-Bostwick CA, Katsikis PD.
Arth. Rheum 63:3563-74, 2011
4th Aegean Conference on the Crossroads between Innate and Adaptive Immunity.
Schoenberger SP, Pulendran B, Katsikis PD.
Nat Immunol. 13:7-10, 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, Katsikis PD.
J. Immunol. 186:4599–4608, 2011
Katsikis PD, Mueller YM, Villinger F.
The cytokine network of acute HIV infection: a promising target for vaccines and therapy to reduce viral set-point?
PLOS Pathogens 7: e1002055, 2011
IL-15 treatment during acute simian immunodeficiency virus (SIV) infection increases viral set point and accelerates disease progression despite the induction of stronger SIV-specific CD8+ T cell responses.
Mueller YM, Do DH, Altork SR, Artlett CM, Gracely EJ, Katsetos CD, Legido A, Villinger F, Altman JD, Brown CR, Lewis MG, Katsikis PD.
J Immunol. 180:350-60, 2008
Memory CD8+ T cells require CD28 costimulation.
Borowski AB, Boesteanu AC, Mueller YM, Carafides C, Altman JD, Jennings SR, Katsikis PD.
J. Immunol. 179:6494-6503, 2007
Interleukin-15 increases effector memory CD8+ t cells and NK Cells in simian immunodeficiency virus-infected macaques.
Mueller YM, Petrovas C, Bojczuk PM, Dimitriou ID, Beer B, Silvera P, Villinger F, Cairns JS, Gracely EJ, Lewis MG, Katsikis PD.
J Virol. 79:4877-85, 2005
IL-15 enhances survival and function of HIV-specific CD8+ T cells.
Mueller YM, Bojczuk PM, Halstead ES, Kim AH, Witek J, Altman JD, Katsikis PD.
Blood. 101:1024-9, 2003
In vivo stimulation of CD137 broadens primary antiviral CD8+ T cell responses.
Halstead ES, Mueller YM, Altman JD, Katsikis PD.
Nat Immunol. 3:536-41, 2002
Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells.
Mueller YM, De Rosa SC, Hutton JA, Witek J, Roederer M, Altman JD, Katsikis PD.
Immunity. 15:871-82, 2001