Peter D. Katsikis MD, PhD
Professor and Head of the Department of Immunology
Infection and Immunity Research Group (IIG)
p.katsikis@erasmusmc.nl
+31-107044188 (Administrative Assistant)
Erasmus MC, University Medical Center
Dr. Molewaterplein 40, 3015 GD Rotterdam, The Netherlands
Yvonne M. Müller, PhD
Assistant Professor
Department of Immunology
Infection and Immunity Research Group (IIG)
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, understand why these cells fail in certain chronic infections and cancer, and find treatments or vaccines to improve such immunity.
To understand the molecular pathways that control of CTL responses, we study the signaling requirements and gene regulation networks that enable successful CTL responses. Our laboratory utilizes animal models that employ influenza virus and Listeria monocytogenes infections and mouse tumor models to decipher the regulation in CTL immunity. A rapid in vitro CTL exhaustion method has been developed to facilitate the testing of exhaustion reversal strategies and this has led to the identification of a number of compounds that can improve anti-tumor immunity.
Another central aim of our research is to understand why CTL fail in HIV infection and how to eliminate the latent HIV reservoir. This latent HIV reservoir persists in patients even after many years of viral suppression with highly active antiretroviral therapy. Strategies to reactivate HIV from latently infected cells and to kill these cells via innate or adaptive immune responses are being explored together within a larger consortium of Cure researchers at Erasmus MC (EHEG) and beyond. Our team is developing specific reagents that can kill cells in which HIV has awakened from its latent state.
A third area of research in our laboratory is the development of 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 neopeptide and adjuvants. Novel adjuvants that induce potent T cell immunity against neopeptides are being developed and testing in animals. By combining such adjuvants with neopeptides we generate cancer vaccines that are tested in tumor models.
Finally, we are part of the EU-funded ImmunAID international consortium with the focus of performing translational research on systemic autoinflammatory diseases (SAID). This consortium has recruited the largest cohort of non-monogenic SAID patients from throughout Europe and is generating unique multiomic data. Our laboratory is generating unique datasets by performing microRNA, mRNA and proteomics analysis on Immune subsets in the blood of these patients. The goal is to discover biomarkers that can assist in diagnosis and treatment of these patients.
Group members
- Peter Katsikis
- Yvonne Mueller
- Kou Hioki, Postdoctoral Scientist
- Gennaro Iaconis, Postdoctoral Scientist
- Ling Li, PhD student
- Inge Brouwers-Haspels, Research Assistant
- Marjan van Meurs, Research Assistant
- Danique Laport, Research Assistant
- Iris van Zuijen, Research Assistant
- Renske den Dekker, Research Assistant
- Kevin de Vos, Research Assistant
- Marlous Wildemans, Research Assistant
- Harm de Wit, Research Assistant
Past members since 2018:
- Manzhi Zhao, PhD student
- Caoimhe Kiernan, Postdoctoral Scientist
- Melisa Castro Eiro, Postdoctoral Scientist
- Merel Wilmsen, Research Assistant
- Tamara van Wees, Research Assistant
- Tessa Alofs, Research Assistant
Selected Publications
(See all publications for Peter Katsikis in Pubmed)
Katsikis PD, Ishii KJ, Schliehe C: Challenges in developing personalized neoantigen cancer vaccines.
Nat Rev Immunol. Oct 2. doi: 10.1038/s41577-023-00937-y. 2023
Castro Eiro MD, Hioki K, Li L, Wilmsen MEP, Kiernan CH, Brouwers–Haspels I, van Meurs M, Zhao M, de Wit H, Grashof DGB, van de Werken HJG, Mueller YM, Schliehe C, Temizoz B, Kobiyama K, Ishii KJ, Katsikis PD: TLR9 plus STING agonist adjuvant combination induces potent neopeptide T cell immunity and improves immune checkpoint blockade efficacy in a tumor model.
Journal of Immunology (In press)
Vietsch EE, Latifi D, Verheij M, van der Oost EWA, de Wilde RF, Haen R, van den Boom AL, Koerkamp BG, Doornebosch PG, van Verschuer VMT, Ooms AHAG, Mohammad F, Willemsen M, Aerts JGJV, Krog RT, de Miranda NFCC, van den Bosch TPP, Mueller YM, Katsikis PD, van Eijck CCHJ: B cell immune profiles in dysbiotic vermiform appendixes of pancreatic cancer patients.
Frontiers in Immunology 2023, DOI 10.3389/fimmu.2023.1230306
Li L, Zhao M, Kiernan CH, Castro Eiro MD, van Meurs M, Brouwers-Haspels I, Wilmsen MEP, Grashof DGB, van de Werken HJG, Hendriks RW, Mueller YM, Katsikis PD: Ibrutinib directly reduces CD8+T cell exhaustion independent of BTK.
Front Immunol. 14:1201415, 2023.
Zhao M, Li L, Kiernan CH, Castro Eiro MD, Dammeijer F, van Meurs M, Brouwers-Haspels I, Wilmsen MEP, Grashof DGB, van de Werken HJG, Hendriks RW, Aerts JG, Mueller YM, Katsikis PD: Overcoming immune checkpoint blockade resistance in solid tumors with intermittent ITK inhibition.
Sci Rep. 13:15678, 2023
Wahadat MJ, van Tilburg SJ, Mueller YM, de Wit H, Van Helden-Meeuwsen CG, Langerak AW, Gruijters MJ, Mubarak A, Verkaaik M, Katsikis PD, Versnel MA, Kamphuis S: Targeted multiomics in childhood-onset SLE reveal distinct biological phenotypes associated with disease activity: results from an explorative study.
Lupus Sci Med. 10:e000799, 2023
Prins HAB, Crespo R, Lungu C, Rao S, Li L, Overmars RJ, Papageorgiou G, Mueller YM, Stoszko M, Hossain T, Kan TW, Rijnders BJA, Bax HI, van Gorp ECM, Nouwen JL, de Vries-Sluijs TEMS, Schurink CAM, de Mendonça Melo M, van Nood E, Colbers A, Burger D, Palstra RJ, van Kampen JJA, van de Vijver DAMC, Mesplède T, Katsikis PD, Gruters RA, Koch BCP, Verbon A, Mahmoudi T, Rokx C: The BAF complex inhibitor pyrimethamine reverses HIV-1 latency in people with HIV-1 on antiretroviral therapy.
Sci Adv. 9:eade6675, 2023
Jongkees MJ, Geers D, Hensley KS, Huisman W, GeurtsvanKessel CH, Bogers S, Gommers L, Papageorgiou G, Jochems SP, den Hollander JG, Schippers EF, Ammerlaan HSM, Bierman WFW, van der Valk M, Berrevoets MAH, Soetekouw R, Langebeek N, Bruns AHW, Leyten EMS, Sigaloff KCE, van Vonderen MGA, Delsing CE, Branger J, Katsikis PD, Mueller YM, de Vries RD, Rijnders BJA, Brinkman K, Rokx C, Roukens AHE: Immunogenicity of an Additional mRNA-1273 SARS-CoV-2 Vaccination in People With HIV With Hyporesponse After Primary Vaccination.
J Infect Dis. 227:651-662, 2023
Kumova OK, Galani IE, Rao A, Johnson H, Triantafyllia V, Matt SM, Pascasio J, Gaskill PJ, Andreakos E, Katsikis PD, Carey AJ: Severity of neonatal influenza infection is driven by type I interferon and oxidative stress.
Mucosal Immunol. 15:1309-1320, 2022
Hensley KS, Jongkees MJ, Geers D, GeurtsvanKessel CH, Mueller YM, Dalm VASH, Papageorgiou G, Steggink H, Gorska A, Bogers S, den Hollander JG, Bierman WFW, Gelinck LBS, Schippers EF, Ammerlaan HSM, van der Valk M, van Vonderen MGA, Delsing CE, Gisolf EH, Bruns AHW, Lauw FN, Berrevoets MAH, Sigaloff KCE, Soetekouw R, Branger J, de Mast Q, Lammers AJJ, Lowe SH, de Vries RD, Katsikis PD, Rijnders BJA, Brinkman K, Roukens AHE, Rokx C.
Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.
PLoS Med. 19:e1003979, 2022
Kaiser FMP, Gruenbacher S, Oyaga MR, Nio E, Jaritz M, Sun Q, van der Zwaag W, Kreidl E, Zopf LM, Dalm VASH, Pel J, Gaiser C, van der Vliet R, Wahl L, Rietman A, Hill L, Leca I, Driessen G, Laffeber C, Brooks A, Katsikis PD, Lebbink JHG, Tachibana K, van der Burg M, De Zeeuw CI, Badura A, Busslinger M: Biallelic PAX5 mutations cause hypogammaglobulinemia, sensorimotor deficits, and autism spectrum disorder.
J Exp Med. 219:e20220498, 2022
Petkau G, Mitchell TJ, Chakraborty K, Bell SE, D Angeli V, Matheson L, Turner DJ, Saveliev A, Gizlenci O, Salerno F, Katsikis PD, Turner M: The timing of differentiation and potency of CD8 effector function is set by RNA binding proteins.
Nat Commun. 13:2274, 2022
Mueller YM, Schrama TJ, Ruijten R, Schreurs MWJ, Grashof DGB, van de Werken HJG, Lasinio GJ, Alvarez de la Sierra D, Kiernan CH, Castro Eiro MD, van Meurs M, Brouwers-Haspels I, Zhao M, Li L, de Wit H, Ouzounis CA, Wilmsen MEP, Alofs TM, Laport DA, van Wees T, Kraker G, Jaimes MC, Van Bockstael S, Hernández-González M, Rokx C, Rijnders BJA, Pujol-Borrell R, Katsikis PD: Stratification of hospitalised COVID-19 patients into clinical severity progression groups by immuno-phenotyping and machine learning.
Nat Commun. 13:915, 2022
Hope JL, Zhao M, Stairiker CJ, Kiernan CH, Carey AJ, Mueller YM, van Meurs M, Brouwers-Haspels I, Otero DC, Bae EA, Faso HA, Maas A, de Looper H, Fortina PM, Rigoutsos I, Bradley LM, Erkeland SJ, Katsikis PD: “MicroRNA-139 Expression is Dispensable for the Generation of Influenza-Specific CD8+ T cell Responses”.
J Immunol. volume 208, 2022
Stavast CJ, van Zuijen I, Karkoulia E, Özçelik A, van Hoven-Beijen A, Leon LG, Voerman JSA, Janssen GMC, van Veelen PA, Burocziova M, Brouwer RWW, van IJcken WFJ, Maas A, Bindels EM, van der Velden VHJ, Schliehe C, Katsikis PD, Alberich-Jorda M, Erkeland SJ: The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis.
Leukemia (in press), 2021
Rao S, Lungu C, Steijaert T, Crespo R, Palstra RJ, Rokx C, Mueller YM, van Kampen J, Verbon A, Katsikis PD, Boucher C, Gruters R, Mahmoudi T: Induction of selective cell death in HIV-1 infected cells by DDX3 inhibitors leads to depletion of the inducible reservoir.
Nat Commun. 12:2475, 2021
van der Sijde F, Mustafa DAM, Vietsch EE, Katsikis PD, van Eijck CHJ: Circulating Immunological Biomarkers: Prognosis of Pancreatic Cancer Patients Reflected by the Immune System.
Pancreas. 50:933-941, 2021
Gharbharan A, Jordans C, GeurtsvanKessel C, den Hollander J, Karim F, Mollema F, Stalenhoef-Schukken J, Dofferhof A, Ludwig I, Koster A, Hassing RJ, Bos J, van Pottelberge G, Vlasveld I, Ammerlaan H, van Leeuwen – Segarceanu E, Miedema J, van der Eerden M, Schrama T, Papageorgiou G, te Boekhorst P, Swaneveld F, Mueller Y, Scheurs M, van Kampen JJA, Rockx B, Okba N, Katsikis PD, Koopmans M, Haagmans B, Rokx C, Rijnders B: Effects of Potent Neutralizing Antibodies from Convalescent Plasma in Patients Hospitalized for Severe SARS-CoV-2 Infection.
Nat Commun. 12:3189, 2021
Hope JL, Spantidea PI, Stairiker CJ, Rijsbergen LC, van Meurs M, Brouwers-Haspels I, Mueller YM, Nelson DJ, Aerts JGJV, Katsikis PD: Microenvironment-dependent gradient of CTL exhaustion in the AE17sOVA murine mesothelioma tumor model.
Front. Immunol. 10:3074, 2020
Zhao M, Kiernan CH, Stairiker CJ, Leon LG, Meurs M, Brouwers-Haspels I, Boers R, Boers J, Gribnau J, IJcken WFJ, Bindels EM, Hoogenboezem RM, Erkeland SJ, Mueller YM, Katsikis PD: Rapid in vitro generation of bona fide exhausted CD8+ T cells is accompanied by Tcf7 promotor methylation.
PLoS Pathog. 16(6): e1008555, 2020
Dammeijer F, Van Gulijk M, Mulder EE, Lukkes M, Klaase L, van den Bosch T, van Nimwegen M, Lau SP, Latupeirissa K, Schetters S, van Kooyk Y, Boon L, Moyaart A, Mueller YM, Katsikis PD, Eggermont AM, Vroman H, Stadhouders R, Hendriks RW, Thüsen JV, Grünhagen DJ, Verhoef C, van Hall T, Aerts JG.: Selective PD-L1 blockade in the tumor-draining lymph node induces effective anti-tumor T-cell immunity.
Cancer Cell. 38(5):685-700, 2020
Stoszko M, Al-Hatmi AMS, Skriba A, Roling M, Ne E, Crespo R, Mueller YM, Najafzadeh MJ, Kang J, Ptackova R, Biswas P, Bertoldi A, Kan TW, de Crignis E, Sulc M, Lebbink JHG, Rokx C, Verbon A, van Ijcken W, Katsikis PD, Palstra RJ, Havlicek V, de Hoog S, Mahmoudi T: Gliotoxin, identified from a screen of fungal metabolites, disrupts 7SK snRNP, releases P-TEFb and reverses HIV-1 latency.
Sci Adv. 6(33): eaba6617, 2020
Stairiker CJ, van Meurs M, Leon LG, Brouwers-Haspels I, Rijsbergen LC, Mueller YM, Katsikis PD*: Heatr9 is an infection responsive gene that affects cytokine production in alveolar epithelial cells.
PLoS One 15(7): e0236195, 2020
Kumova OK, Fike A, Thayer JL, Nguyen LT, Chang Mell J, Pascasio J, Stairiker CJ, Leon LG, Katsikis PD, Carey AJ: Lung transcriptional unresponsiveness and loss of early viral control in influenza virus infected neonates is prevented by intranasal Lactobacillus rhamnosus GG.
PLoS Pathog. 15: e1008072, 2019
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
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.
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