Dr. D. A. J. (Debby) van Riel

Debby van Riel - Associate professor

Viral infections are a major burden of disease worldwide, and in recent years we have learned that even mild infections can contribute to the development of disease in multiple organ system. The research in the RielScience team aims to understand how a viral infection results in the development of disease in the acute and/or post-acute phase. Therefore, we study the systemic pathogenesis of respiratory virus infections, including influenza A viruses, coronaviruses and enterovirus-D68. Furthermore, we focus on the neuropathogenesis of a broad range of virus infections, including influenza A viruses, coronaviruses, enterovirus and recently monkeypoxvirus.

In recent years the team has shown that many respiratory viruses can spread beyond the respiratory tract, where they affect the central nervous and cardiovascular system. Furthermore, we have shown that many respiratory viruses can enter the CNS, including almost all influenza A viruses and SARS-CoV-2 viruses, where they trigger local inflammatory responses that might last in the post-acute phase. In our studies we combine in vivo with in vitro models to unravel the virus-host interaction at the molecular- to host level. Our in vitro models are recently established scalable, reproducible and relevant human model systems, such as stem cell derived neural cultures that contain multiple cell types. Our research is published in many high ranked journals including Science, Nature Com, Trends in Neurosci, NEJM, Am J Pathol, Acta Neuropathol Com, PloS Path, J Infect Dis, etc. (see publications).

We feel that understanding the fundamental mechanisms how viruses can spread through a host, target different organ system, and trigger organ dysfunction is essential to
(1) identify common phenotypic characteristics of viruses that predict the virulence in a specific host/organ system
(2) screen new (emerging) viruses for their potential to cause disease,
(3) develop preventive or therapeutic interventions strategies and
(4) validate intervention strategies.

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Recent key publication on the neuropathogenesis of viruses:

1. The neuropathogenesis of highly pathogenic avian influenza H5Nx viruses in mammalian species including humans.
   Bauer L, Benavides FFW, Veldhuis Kroeze EJB, de Wit E, van Riel D. Trends Neurosci. 2023 Sep 6:S0166-2236(23)00190-X. doi: 10.1016/j.tins.2023.08.002.
2. Dissecting the neurotropism and neurovirulence of MPXV using human stem cell-based models
   Bauer L, Giussani S, Palazzi N, Zare F, Colombo, E, Pinci E, Leijten L, Smeenk H, Embregts C, Silva M, Spoor J, Dirven C, Gao Z, Bolleboom A, Verstrepen B, Schuele L, de Vrij F, Kushner S, Oude Munnink B, Davila-Velderrain J, van Riel D*, Harschnitz O* BioRxiv doi:https://doi.org/10.1101/2023.08.25.554849.
3. Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.
   Siegers JY, Ferreri L, Eggink D, Veldhuis Kroeze EJB, Te Velthuis AJW, van de Bildt M, Leijten L, van Run P, de Meulder D, Bestebroer T, Richard M, Kuiken T, Lowen AC, Herfst S, van Riel D. PLoS Pathog. 2023 Mar 10;19(3):e1011214. doi: 10.1371/journal.ppat.1011214.
4. Do SARS-CoV-2 Variants Differ in Their Neuropathogenicity?
   Bauer L, van Riel D. mBio. 2023 Feb 28;14(1):e0292022. doi: 10.1128/mbio.02920-22.
5. In vitro and in vivo differences in neurovirulence between D614G, Delta And Omicron BA.1 SARS-CoV-2 variants.
   Bauer L, Rissmann M, Benavides FFW, Leijten L, van Run P, Begeman L, Veldhuis Kroeze EJB, Lendemeijer B, Smeenk H, de Vrij FMS, Kushner SA, Koopmans MPG, Rockx B, van Riel D. Acta Neuropathol Commun. 2022 Sep 5;10(1):124. doi: 10.1186/s40478-022-01426-4.
6. Detection of intrathecal antibodies to diagnose enterovirus infections of the central nervous system.
   Sooksawasdi Na Ayudhya S, Sips GJ, Bogers S, Leijten LME, Laksono BM, Smeets LC, Bruning A, Benschop K, Wolthers K, van Riel D, GeurtsvanKessel CH. J Clin Virol. 2022 Jul;152:105190. doi: 10.1016/j.jcv.2022.105190.
7. The neuroinvasiveness, neurotropism, and neurovirulence of SARS-CoV-2.
   Bauer L, Laksono BM, de Vrij FMS, Kushner SA, Harschnitz O, van Riel D.Trends Neurosci. 2022 May;45(5):358-368. doi: 10.1016/j.tins.2022.02.006.

Recent publications on the systemic pathogenesis of viruses

1. CYP19A1 mediates severe SARS-CoV-2 disease outcome in males.
   Stanelle-Bertram S, Beck S, Mounogou NK, Schaumburg B, Stoll F, Al Jawazneh A, Schmal Z, Bai T, Zickler M, Beythien G, Becker K, de la Roi M, Heinrich F, Schulz C, Sauter M, Krasemann S, Lange P, Heinemann A, van Riel D, Leijten L, Bauer L, van den Bosch TPP, Lopuhaä B, Busche T, Wibberg D, Schaudien D, Goldmann T, Lüttjohann A, Ruschinski J, Jania H, Müller Z, Pinho Dos Reis V, Krupp-Buzimkic V, Wolff M, Fallerini C, Baldassarri M, Furini S, Norwood K, Käufer C, Schützenmeister N, von Köckritz-Blickwede M, Schroeder M, Jarczak D, Nierhaus A, Welte T, Kluge S, McHardy AC, Sommer F, Kalinowski J, Krauss-Etschmann S, Richter F, von der Thüsen J, Baumgärtner W, Klingel K, Ondruschka B; GEN-COVID Multicenter Study Group; Renieri A, Gabriel G.Cell Rep Med. 2023 Sep 19;4(9):101152. doi: 10.1016/j.xcrm.2023.101152.
2. The pro-inflammatory response to influenza A virus infection is fueled by endothelial cells.
   Bauer L, Rijsbergen LC, Leijten L, Benavides FF, Noack D, Lamers MM, Haagmans BL, de Vries RD, de Swart RL, van Riel D. Life Sci Alliance. 2023 Apr 18;6(7):e202201837
3. The pathogenesis and virulence of enterovirus-D68 infection.
   Sooksawasdi Na Ayudhya S, Laksono BM, van Riel D. Virulence. 2021 Dec;12(1):2060-2072
4. In Vivo Models to Study the Pathogenesis of Extra-Respiratory Complications of Influenza A Virus Infection.
   Veldhuis Kroeze E, Bauer L, Caliendo V, van Riel D. Viruses. 202.
5. Temporal Kinetics of RNAemia and Associated Systemic Cytokines in Hospitalized COVID-19 Patients.
   van Riel D, Embregts CWE, Sips GJ, van den Akker JPC, Endeman H, van Nood E, Raadsen M, Bauer L, van Kampen J, Molenkamp R, Koopmans M, van de Vijver D, Geurts van Kessel CH.mSphere. 2021 Jun 30;6(3):e0031121
6. A High-Fat Diet Increases Influenza A Virus-Associated Cardiovascular Damage.
   Siegers JY, Novakovic B, Hulme KD, Marshall RJ, Bloxham CJ, Thomas WG, Reichelt ME, Leijten L, van Run P, Knox K, Sokolowski KA, Tse BWC, Chew KY, Christ AN, Howe G, Bruxner TJC, Karolyi M, Pawelka E, Koch RM, Bellmann-Weiler R, Burkert F, Weiss G, Samanta RJ, Openshaw PJM, Bielefeldt-Ohmann H, van Riel D*, Short KR*.J Infect Dis. 2020 Aug 4;222(5):820-831
7. Role of Endothelial Cells in the Pathogenesis of Influenza in Humans.
   Short KR, Kuiken T, van Riel D. J Infect Dis. 2019 Oct 22;220(11):1859-1860.
8. Mini viral RNAs act as innate immune agonists during influenza virus infection.
   Te Velthuis AJW, Long JC, Bauer DLV, Fan RLY, Yen HL, Sharps J, Siegers JY, Killip MJ, French H, Oliva-Martín MJ, Randall RE, de Wit E, van Riel D, Poon LLM, Fodor E. Nat Microbiol. 2018 Nov;3(11):1234-1242.

Others:

1. The pathogenesis of zoonotic viral infections: Lessons learned by studying reservoir hosts.
   Begeman L, van Riel D, Koopmans MPG, Kuiken T.Front Microbiol. 2023 Mar 28;14:1151524. doi: 10.3389/fmicb.2023.1151524.
2. Next-generation vaccine platforms for COVID-19.
   van Riel D, de Wit E.Nat Mater. 2020 Aug;19(8):810-812. doi: 10.1038/s41563-020-0746-0.
3. A Novel Coronavirus Emerging in China - Key Questions for Impact Assessment.
   Munster VJ, Koopmans M, van Doremalen N, van Riel D, de Wit E.N Engl J Med. 2020 Feb 20;382(8):692-694.

Debby has received several grants and fellowships that support her research group, including a Veni, Erasmus MC fellowship, Vidi, EUR fellowship and Aspasia (total > 1.5 million Euro).

In addition, she has been part of the EU consortia FLUPIG, ANTIGONE, and is currently part of KAPPA-FLU.

In addition, Debby received the Beijerinck premium in 2015 (2 yearly award for promising early career scientists within virology research in the Netherlands), the ESWI Award in 2017 (3-yearly international awards for the most promising body of work in influenza virus research from European Scientific Working group on Influenza) and she is a former member of the Young Erasmus Academy and currently the young scientist ambassador at the ESWI.

Longstanding (inter)national collaborations:

Prof. Dr. Gülsah Gabriel, Heinrich-Pette Institute (HPI) Hamburg, Germany:
Debby is employed as a guest scientist at the HPI. This collaboration is based on the joint interest in the pathogenesis of influenza virus infections. This collaboration resulted in several joint publications (Stanelle-Bertram S 2023; Thiele 2020; Anfasa 2017; Betram 2017; van Riel 2016; Otte 2016 and Siegers 2014)

Dr. Emmie de Wit, RML NIH, Montana US:
The Collaboration with Dr de Wit is based on on our joint interest in the (neuro) pathogenesis of respiratory viruses including 1918 H1N1 Influenza virus (Spanish flu)
This collaboration resulted in several joint publications (Bauer 2023; van Riel 2020; Munster 2020; te Velthuis 2018; de Wit 2018; Chutinimitkul 2010; van Riel 2010; de Wit 2010; van Riel 2007; Munster 2007; van Riel 2006).

Dr. Femke de Vrij and Prof. Kushner, department of Psychiatry, Erasmus MC, The Netherlands:
This collaboration is based on the development of human induced pluripotent stem cell derived neural models that can be used to study the effect of virus infections in biosafety level 2 and 3 conditions. This resulted in several joint publications (Bauer 2022; Bauer 2022; Bauer 2021; Anfasa 2017).

Dr Oliver Harschnitz, Human Technopole, Milan, Italy:
The collaboration with the team of Dr. Harschnitz is based on our joint interest in how viruses affect the neural homeostasis using stem cell based neural models. This resulted in 2 joint publications so far (Bauer 2023; Bauer 2022).

The RielScience team consists of an enthusiastic group of scientists with different expertise, background and training.

Current members: Debby van Riel – PI, Associate Professor Brigitta Laksono – Postdoc Lisa Bauer – Postdoc Edwin Veldhuis-Kroeze- Veterinary Pathologist Lonneke Leijten – Research technician Syriam Sooksawasdi Na Ayudhya – PhD student Feline Benavides – PhD student Alisha Biharie – BSc Student Anouk Montenarie – MSc Student