About our research group/lab
Research
The HerpeslabNL aims to elucidate the virus and host factors involved in the immune control and pathogenesis of the human neurotropic herpes simplex viruses (HSV) and varicella zoster virus (VZV) in their natural host.
A hallmark of these herpesviruses is their ability to establish a lifelong latent infection after primary infection of neurons in sensory ganglia (HSV) or along the entire neuraxis (VZV). Reactivation of latent virus, which occasionally leads to recrudescent disease, is controlled by innate and adaptive immunity. Virus-specific immune responses are commonly beneficial (control of latent infection in sensory neurons), but can also cause detrimental disease affecting the eye (uveitis and keratitis) or the brain (encephalitis and potentially Alzheimer’s disease). The HerpeslabNL has developed a unique infrastructure to acquire human clinical specimens in combination with state-of-the-art methodologies to characterize the virus status (genome, proteome and transcriptome), the virus’ cell tropism, and the innate and adaptive cell types present at the site of infection including their antigen-specificity and effector functions. This enables the identification of the key host and virus factors that determine the clinical outcome of alpha-herpesvirus infections and disease.
The ultimate goal of our research is to develop novel intervention strategies aimed to prevent virus reactivation and herpesvirus-induced pathogenesis.
Team, alumni, and dissertations
Current team:
 |
 |
| Amber Schotting Undergraduate student Email: a.schotting@erasmusmc.nl |
Fulya Koc Undergraduate student Email: f.koc@erasmusmc.nl |
 |
|
|
Jochem Weekers |
|
|
|
|
| Ahmad Seyar Rashidi Graduate student Email: a.rashidi@erasmusmc.nl |
Diana N. Tran Graduate student Email d.tran@erasmusmc.nl |
 |
 |
| Lex Havelaar Graduate student Email: a.havelaar@erasmusmc.nl |
Mark Power Graduate student Email: m.power@erasmusmc.nl |
 |
 |
| Anaïs M.T.Y. Wiech Graduate student Email: a.wiech@erasmusmc.nl |
Sem M. van ‘t Geloof Technician Email: s.vantgeloof@erasmusmc.nl |
|
|
|
| Fatiha Zaaraoui-Boutahar Technician Email: f.zaaraoui@erasmusmc.nl |
Tamana Khemai-Mehraba Technician Email: t.mehraban@erasmusmc.nl |
|
|
 |
|
Werner J.D. Ouwendijk |
Michiel van Gent Assistant professor Email: m.vangent@erasmusmc.nl ORCID ID |
 |
|
| Maaike Moelker-Hang Project Manager - Grant Advisor Email: m.moelker@erasmusmc.nl |
Georges M.G.M. Verjans Associate professor (PI) Email: g.verjans@erasmusmc.nl ORCID ID |
Alumni:
| Post-doctoral fellows |
Current position | |
| Gulce Sari | 2022-2023 | Post-doc at Dept Gastroenterology and Hepatology (Erasmus MC) |
| Peter-Paul Unger |
2019 – 2021 |
Scientist at Thermo Fisher Scientific (Leiden, Netherlands) |
| Eveline D. de Geus |
2014 – 2015 |
Post-doc at Hudson Institute of Medical Research (Melbourne, Australia) |
| Graduate students | Current position | |
| Shirley Braspenning | 2017 - 2020 |
Post-doc at NYU Langone Health (New York, USA) |
| Gijs P. van Nierop |
2010 – 2018 |
Post-doc at Erasmus MC (Rotterdam, Netherlands) Link to thesis G.P. van Nierop (2018) |
| Erik Schaftenaar |
2012 – 2016 |
Microbiologist at St. Antonius hospital (Utrecht, Netherlands) Link to thesis E. Schaftenaar (2016) |
| Monique van Velzen |
2008 – 2013 |
Assistant professor at LUMC (Leiden, Netherlands) Link to thesis M. van Velzen (2013) |
| Rui Duan |
2004 – 2009 |
|
| Jeroen Maertzdorf |
1998 – 2002 |
Max Planck Institute for Infection Biology (Berlin, Germany) Link to thesis J. Maertzdorf (2002) |
| Lies Remeijer |
1997 – 2002 |
Chief ophthalmologist (Rotterdam, Netherlands) Link to thesis L. Remeijer (2002) |
Projects
Ongoing projects’ & ‘Completed projects |
Ongoing |
|
|
|
|
|
|
Large Scale T Cell Epitope Discovery: Local and Systemic T-cell Response to Herpes Simplex Virus Project Aims: To characterize the phenotype, functional characteristics and fine antigen specificity of virus-specific T-cells in HSV-1 infected human corneas and trigeminal ganglia. Team: Michiel van Gent & Georges M.G.M. Verjans International collaboration: David M. Koelle (University of Washington, Seattle WA) Funding: National Institute of Allergy and Infectious Diseases (75N93019C00063-0-9999-1) |
Role of VZV latency transcript (VLT) and ORF63 in latency and reactivation Project Aims: To determine the role of VLT and ORF63 in latency establishment/ maintenance/ reactivation in human neurons ex vivo, in situ and in vitro. Team: Lex Havelaar,Shirley E. Braspenning, Werner J.D. Ouwendijk & Georges M.G.M. Verjans International collaboration: Paul (Kip) R. Kinchington (University of Pittsburgh, Pittsburgh, PA) Funding: National Institute of Allergy and Infectious Diseases (R01-AI151290-01A1) |
Cell death in the central nervous system: mechanisms and impact on disease pathogenesis. Project Aims: To identify the types of cell death that occur in diseases in the CNS, identify the molecular mechanisms involved, and decipher the impact on pathology. Team: Ahmad Seyar Rashidi & Georges M.G.M. Verjans International collaboration: Søren R. Paludan (Aarhus University Aarhus, Denmark) Funding: Lundbeckfonden (R276-2018-192) |
Completed projects |
| Cutaneous Pathogen-Specific Tissue Resident Memory T Cells in Human Aging Project Aims: To determine the role of HSV-1 reactive T-cells in the pathophysiology of Alzheimer’s disease. Team: Michiel van Gent, Peter-Paul Unger & Georges M.G.M. Verjans International collaboration: David M. Koelle (University of Washington, Seattle WA) Funding: National Institute of Aging (R01-AG064800-02S1) |
| Human organotypic brain slice model: a novel platform to study virus-induced neuropathology Project Aims: To determine the virus tropism and pathogenesis of neurotropic viruses using the human ex-vivo brain slice culture platform to be developed. Team: Diana N. Tran & Georges M.G.M. Verjans International collaboration: not applicable Funding: Erasmus MC: Human Disease Model Award |
| Single cell analysis of T-cell receptors and transcriptome in tissue of multiple sclerosis patients Project Aims: To determine the fine antigen specificity, function and spatial orientation of dominant CD8 T-cells in brain lesions of multiple sclerosis patients. Team: Peter-Paul Unger & Georges M.G.M. Verjans International collaboration:Stephen J. Elledge (Harvard Medical School, Boston MA) & Roland Martin (University of Zurich, Zurich, Switzerland) Funding: Dutch MS Research Foundation (17-995 MS) |
Publications
| 2023 |
|
Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants. |
|
ER stress induces caspase-2-tBID-GSDME-dependent cell death in neurons lytically infected with herpes simplex virus type 2. |
|
Current perspectives on the management of herpesvirus infections in solid organ transplant recipients. |
|
Varicella-zoster virus proteome-wide T-cell screening demonstrates low prevalence of virus-specific CD8 T-cells in latently infected human trigeminal ganglia. |
| 2022 |
| Selective retention of virus-specific tissue-resident T cells in healed skin after recovery from herpes zoster. Laing KJ, Ouwendijk WJD, Campbell VL, McClurkan CL, Mortazavi S, Waters ME, Krist MP, Tu R, Nguyen N, Basu K, Miao C, Schmid DS, Johnston C, Verjans GMGM, Koelle DM. Nature Communications. 2022 Nov 15. doi: 10.1038/s41467-022-34698-4 |
|
T-cells in human trigeminal ganglia express canonical tissue-resident memory T-cell markers. Unger PPA, Oja AE, Khemai-Mehraban T, Ouwendijk WJ, Hombrink P, Verjans GMGM. J Neuroinflammation. 2022 Oct 06. doi: 10.1186/s12974-022-02611-x |
|
Microglia activate early anti-viral responses upon HSV-1 entry into the brain to counteract development of encephalitis-like disease in mice. |
| 2021 |
| No evidence of aberrant amyloid β and phosphorylated tau expression in herpes simplex virus-infected neurons of the trigeminal ganglia and brain. Tran DN, Bakx AT, van Dis V, Aronica E, Verdijk RM & Ouwendijk WJ. Brain Pathol. 2021 Dec 16. doi: 10.1111/bpa.13044. |
| Mutagenesis of the varicella-zoster virus genome demonstrates that VLT and VLT-ORF63 proteins are dispensable for lytic infection. Braspenning SE, Lebbink RJ, Depledge DP, Schapendonk CME, Anderson LA, Verjans GM, Sadaoka T** & Ouwendijk WJ**. Viruses. 2021 Nov 16. doi: 10.3390/v13112289. |
| The architecture of the simian varicella virus transcriptome. Braspenning SE, Verjans GM, Mehraban T, Messaoudi I, Depledge DP** & Ouwendijk WJ**. PLoS Pathog. 2021 Nov 22. doi: 10.1371/journal.ppat.1010084. |
| Generation of hiPSC-derived low threshold mechanoreceptors containing axonal termini resembling bulbous sensory nerve endings and expressing Piezo1 and Piezo2. Zhu S, Stanslowsky N, Fernández-Trillo J, Mamo TM, Yu P, Kalmbach N, Ritter B, Eggenschwiler R, Ouwendijk WJ, Mzinza D, Tan L, Leffler A, Spohn M, Brown RJP, Kropp KA, Kaever V, Ha TC, Narayanan P, Grundhoff A, Förster R, Schambach A, Verjans GM, Schmidt M, Kispert A, Cantz T, Gomis A, Wegner F & Viejo-Borbolla A. Stem Cell Res. 2021 Oct 21. doi: 10.1016/j.scr.2021.102535. |
| Local immune control of latent herpes simplex virus type 1 in ganglia of mice and man. St Leger AJ, Koelle DM, Kinchington PR & Verjans GM. Front Immunol. 2021 Sep 15. doi: 10.3389/fimmu.2021.723809 |
| Cluster of symptomatic graft-to-host transmission of herpes simplex virus type 1 in an endothelial keratoplasty setting. Guerra-Assunção JA*, van Kampen JJ*, Roy S, Remeijer L, Breuer J & Verjans GM. Ophthalmol Science. 2021 Aug 11. DOI: 10.1016/j.xops.2021.100051 |
| Comparable infection level and tropism of measles virus and canine distemper virus in organotypic brain slice cultures obtained from natural host species. Laksono BM*, Tran DN*, Kondova I, van Engelen HGH, Michels S, Nambulli S, de Vries RD, Duprex WP, Verjans GM & de Swart RL. Viruses. 2021 Aug 10. doi: 10.3390/v13081582. |
| High levels of neutrophil extracellular traps persist in the lower respiratory tract of critically ill patients with coronavirus disease. Ouwendijk WJ, Raadsen MP, van Kampen JJ, Verdijk RM, von der Thusen JH, Guo L, Hoek RA, van den Akker JP, Endeman H, Langerak T, Molenkamp R, Gommers D, Koopmans MP, van Gorp EC, Verjans GM & Haagmans BL. J Infect Dis. 2021 May 20. doi: 10.1093/infdis/jiab050. |
| Varicella-zoster virus VLT-ORF63 fusion transcript induces broad viral gene expression during reactivation from neuronal latency. Ouwendijk WJ*, Depledge DP*, Rajbhandari L, Lenac Rovis T, Jonjic S, Breuer J, Venkatesan A, Verjans GM & Sadaoka T. Nat Commun. 2020 Dec 10. doi: 10.1038/s41467-020-20031-4. |
|
An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells. |
| 2020 |
| Decoding the architecture of the varicella-zoster virus transcriptome. Braspenning SE, Sadaoka T, Breuer J, Verjans GM, Ouwendijk WJ** & Depledge DP**. mBio. 2020 Oct 6. doi: 10.1128/mBio.01568-20. |
| Alveolar barrier disruption in varicella pneumonia is associated with neutrophil extracellular trap formation. Ouwendijk WJ, van den Ham HJ, Delany MW, van Kampen JJ, van Nierop GP, Mehraban T, Zaaraoui-Boutahar F, van IJcken WF, van den Brand JM, de Vries RD, Andeweg AC & Verjans GM. JCI Insight. 2020 Nov 5. doi: 10.1172/jci.insight.138900. |
| Brain immune cells undergo cGAS/STING-dependent apoptosis during herpes simplex virus type 1 infection to limit type I IFN production. Reinert LS, Rashidi AS*, Tran DN*, Katzilieris-Petras G, Hvidt AK, Gohr M, Fruhwürth S, Bodda C, Thomsen MK, Vendelbo MH, Khan AR, Hansen B, Bergström P, Agholme L, Mogensen TH, Christensen MH, Nyengaard JR, Sen GC, Zetterberg H, Verjans GM & Paludan SR. J Clin Invest. 2021 Jan 4. doi: 10.1172/JCI136824. |
| No evidence of varicella-zoster virus infection in temporal artery biopsies of anterior ischemic optic neuropathy patients with and without giant cell arteritis. Verdijk RM, Ouwendijk WJ, Kuijpers RW & Verjans GM. J Infect Dis. 2021 Jan 4. doi: 10.1093/infdis/jiaa566. |
| Analysis of virus and host proteomes during productive HSV-1 and VZV infection in human epithelial cells. Ouwendijk WJ, Dekker LJ, van den Ham HJ, Lenac Rovis T, Haefner ES, Jonjic S, Haas J, Luider TM & Verjans GM. Front Microbiol. 2020 May 29. doi: 10.3389/fmicb.2020.01179. |
| Ileocolic intussusception as the presenting symptom of primary enteric varicella-zoster virus infection in a 7-month-old infant. Windster JD, Ouwendijk WJ, Sloots CEJ, Verjans GM & Verdijk RM. J Infect Dis. 2020 Jun 29. doi: 10.1093/infdis/jiaa148. |
| Large, stable, contemporary interspecies recombination events in circulating human herpes simplex viruses. Casto AM, Roychoudhury P, Xie H, Selke S, Perchetti GA, Wofford H, Huang ML, Verjans GM, Gottlieb GS, Wald A, Jerome KR, Koelle DM, Johnston C & Greninger AL. J Infect Dis. 2020 Mar 28. doi: 10.1093/infdis/jiz199. |
| Immunobiology of varicella-zoster virus infection. Laing KJ, Ouwendijk WJ, Koelle DM & Verjans GM. J Infect Dis. 2018 Sep 22. doi: 10.1093/infdis/jiy403. |
| Simian varicella virus infects enteric neurons and α4β7 integrin-expressing gut-tropic T-cells in nonhuman primates. Ouwendijk WJ, van Veen S, Mehraban T, Mahalingam R & Verjans GM. Viruses. 2018 Mar 28. doi: 10.3390/v10040156. |
| A spliced latency-associated VZV transcript maps antisense to the viral transactivator gene 61. Depledge DP*, Ouwendijk WJ*, Sadaoka T*, Braspenning SE, Mori Y, Cohrs RJ, Verjans GM** & Breuer J**. Nat Commun. 2018 Mar 21. doi: 10.1038/s41467-018-03569-2. |
| Immunopathology of virus-induced anterior uveitis. De Groot-Mijnes JDF, Chan ASY, Chee SP & Verjans GM. Ocul Immunol Inflamm. 2018 Mar 15. doi: 10.1080/09273948.2018.1439069. |
| Molecular aspects of varicella-zoster virus latency. Depledge DP, Sadaoka T & Ouwendijk WJ. Viruses. 2018 Jun 28. doi: 10.3390/v10070349. |
| Attenuation of simian varicella virus infection by enhanced green fluorescent protein in rhesus macaques. Mahalingam R, Kaufer BB, Ouwendijk WJ, Verjans GM, Coleman C, Hunter M, Das A, Palmer BE, Clambey E, Nagel MA, Traina-Dorge V. J Virol. 2018 Mar 14. doi: 10.1128/JVI.02253-17 |
| Elevated EBNA-1 IgG in MS is associated with genetic ms risk variants. Kreft KL, Van Nierop GP, Scherbeijn SMJ, Janssen M, Verjans GM & Hintzen RQ. Neurol Neuroimmunol Neuroinflamm. 2017 Oct 12. doi: 10.1212/NXI.0000000000000406. |
| Antibody-based immunotherapy of aciclovir resistant ocular herpes simplex virus infections. Bauer D, Keller J, Alt M, Schubert A, Aufderhorst UW, Palapys V, Kasper M, Heilingloh CS, Dittmer U, Laffer B, Eis-Hübinger AM, Verjans GM, Heiligenhaus A, Roggendorf M & Krawczyk A. Virology. 2017 Oct 3. doi: 10.1016/j.virol.2017.09.021. |
| Simian varicella virus inhibits the interferon gamma signalling pathway. Ouwendijk WJ, van Veen S, Mahalingam R & Verjans GM. J Gen Virol. 2017 Oct 10. doi: 10.1099/jgv.0.000925. |
| Phenotypic and functional characterization of T cells in white matter lesions of multiple sclerosis patients. van Nierop GP, van Luijn MM, Michels SS, Melief MJ, Janssen M, Langerak AW, Ouwendijk WJ, Hintzen RQ & Verjans GM. Acta Neuropathol. 2017 Jun 17. doi: 10.1007/s00401-017-1744-4. |
| Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration. González-Motos V, Jürgens C, Ritter B, Kropp KA, Durán V, Larsen O, Binz A, Ouwendijk WJ, Lenac Rovis T, Jonjic S, Verjans GM, Sodeik B, Krey T, Bauerfeind R, Schulz TF, Kaufer BB, Kalinke U, Proudfoot AE, Rosenkilde MM & Viejo-Borbolla A. PLoS Pathog. 2017 May 25. doi: 10.1371/journal.ppat.1006346. |
| Satellite glial cells in human trigeminal ganglia have a broad expression of functional Toll-like receptors. Mitterreiter JG, Ouwendijk WJ, van Velzen M, van Nierop GP, Osterhaus AD & Verjans GM. Eur J Immunol. 2017 Jun 1. doi: 10.1002/eji.201746989. |
|
European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), part 1: diagnosis. |
| European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment. Werner RN, Nikkels AF, Marinović B, Schäfer M, Czarnecka-Operacz M, Agius AM, Bata-Csörgő Z, Breuer J, Girolomoni G, Gross GE, Langan S, Lapid-Gortzak R, Lesser TH, Pleyer U, Sellner J, Verjans GM, Wutzler P, Dressler C, Erdmann R, Rosumeck S & Nast A. J Eur Acad Dermatol Venereol. 2017 Nov 2. doi: 10.1111/jdv.13957. |
Collaborations
Collaborations within Erasmus MC
Collaborations outside of Erasmus MC
- Rotterdam Eye Hospital (Rotterdam, The Netherlands)
- Netherlands Brain Bank (Amsterdam, The Netherlands)
- Stefanie Fruhwürth (University of Gothenburg, Sweden)
- David M. Koelle (University of Washington, Seattle, WA, USA)
- Daniel P. Depledge (Hannover Medical School, Hannover, Germany)
- Tomohiko Sadaoka (Kobe University Graduate School of Medicine, Kobe, Japan)
- Paul (Kip) R. Kinchington (University of Pittsburgh, Pittsburgh, PA, USA)
- Søren R. Paludan (Aarhus University Aarhus, Denmark)
- Stephen J. Elledge (Harvard Medical School, Boston, MA, USA)
News
| 2023 |
| December 2023
Guest Lecture 'Modeling Covid-19 immunity and therapy’ Prof. Joshua T. Schiffer, MD Date: 7 December 2023
|
|
November 2023 Guest Lecture 'Early host defense and immune responses to herpesvirus infections’ Date: 16 november 2023
|
|
July 2023 Ius promovendi awarded to the HerpeslabNL PI: The Erasmus MC’s Doctorate Board has granted dr. G.M.G.M. Verjans the Ius promovendi. |
|
June 2023 Michiel van Gent receives prestigious personal grant (VIDI) from the Dutch Research Council (NWO) to study intrinsic immunity against viral infections of the human nervous system Seven scientists from Erasmus MC receive a grant from NWO for their research. This will enable the laureates to develop an innovative line of research over the next five years and to further expand their own research group. Six Vidis have been awarded and a subsidy through the Open Technology Programme. Michiel van Gent is one of them. |
|
May 2023 Werner Ouwendijk received an ENW-M grant from the Dutch NWO Domain Board Science to investigate how herpesviruses establish latency and how they can reactivate. Link Awakening a sleeping virus Herpesviruses are an important cause of severe diseases in humans and animals. Following infection herpesviruses persist in the host as latent virus (i.e., the virus enters a sleep mode). Later in life, the virus can awaken (reactivation) to cause recurrent disease. I will investigate how herpesviruses establish latency and how they can reactivate. Hereto, I will be using varicella-zoster virus (VZV), the cause of chickenpox and shingles, as a model. More insight into these poorly understood processes will be essential for the development of new therapies that prevent reactivation of VZV and possibly other herpesviruses. |
| 2022 |
|
November 2022 Werner Ouwendijk received an ENW XS grant to explore the link between virus infections and Alzheimer’s disease Link (In Dutch) Impact of virus infections on the development of Alzheimer’s disease. Dr. W.J.D. (Werner) Ouwendijk (Erasmus medisch centrum) Infectious diseases increase the risk of getting Alzheimer's disease. How pathogens contribute to Alzheimer's is unclear. In this study, I will use a powerful and innovative technique to analyze the history of virus infections during the lifetime of an individual. By comparing Alzheimer's patients with non-demented controls, I can identify specific viruses or combinations of virus infections that are associated with the development of Alzheimer's disease. This knowledge encourages further research into how these viruses contribute to the disease and can prioritize the development of new antiviral therapies or vaccines. |
|
October 2022 On Tuesday October 25 2022 Shirley Braspenning successfully defended her PhD dissertation ‘Molecular Biology of Lytic and Latent Varicellovirus Infections’. Link to thesis.
|
|
Juli 2022 Minisymposium "Herpesviruses: molecular interactions between virus and host" Date: 24 october 2022 Synopsis_Bibliography Speakers
|
|
|
March 2022: HerpesLab researcher Dr. Michiel van Gent is awarded a two-year Marie Curie Postdoctoral Fellowship (link). |
May 2022:
Join us
Interested in joining us?
GENERAL POSITIONS:
We are always seeking talented and passionate scientists to join our team, from students to postdocs to staff scientists. If you are interested in joining us, please send an email to HerpeslabNL@erasmusmc.nl and include your CV and contact information for 2-3 references.
