Dr. M. (Mathilde) Richard

Background

Mathilde Richard (1985) is a biochemist engineer and molecular virologist. She completed her PhD in 2010 in France under the supervision of Prof. Bruno Lina studying the resistance of influenza A viruses to neuraminidase inhibitors. She then integrated the Viroscience Department for her post-doctoral studies, which have focused on the pathogenesis, virulence and transmissibility of influenza A viruses, with special emphasis on genetic and phenotypic viral factors involved in the emergence of new pandemics. Since 2018, she is an assistant professor at the Viroscience Department.

Current research lines and team

The research of her team focusses on the understanding of highly pathogenic avian influenza viruses (HPAIV) emergence, their pathogenesis and the development of new vaccination strategies to cope with antigenic diversity in the context of pandemic preparedness.

Work appointments

2022-present: Associate Professor | Work group leader | Department of Viroscience | Erasmus MC, Rotterdam | the Netherlands

2018-2022: Assistant Professor | Work group leader | Department of Viroscience | Erasmus MC, Rotterdam | the Netherlands

2014-2018: Researcher | Department of Viroscience | Erasmus MC, Rotterdam | the Netherlands

2011-2014: Post-Doctoral Researcher | Department of Viroscience | Erasmus MC, Rotterdam | the Netherlands

Education

2007-2010: PhD in Virology (summa cum laude) | University Claude Bernard Lyon 1 (UCBL1) | France 

2007: Master of Science (cum laude) | Microbial Ecology | UCBL 1 | France

2002-2007: Master of Engineering | Biochemistry and Biotechnologies | National Institute of Applied Science, Lyon | France

2005-2006: Visiting research student | Concordia University, Montreal | Canada

Contributions to science

Highly pathogenic avian influenza virus (HPAIV) emergence and host species-specific pathogenesis

Dr. Richard and her team found subtype-specific secondary RNA structures in the hemagglutinin (HA) gene of influenza viruses that might be implicated in the emergence of HPAIV. Her team is developing innovative culture methods for avian primary epithelial and endothelial cells to study the understanding of the host species-specificity of HPAIVs genesis. Her team recently showed that recombination of H7 HAs with foreign RNAs occurs at particular hotspots and hypothesized that RNA recombination of H7 HAs with foreign RNA is facilitated or mediated by snoRNAs.

• Funk M, de Bruin ACM, Spronken MI, Gultyaev AP, Richard M. In Silico Analyses of the Role of Codon Usage at the Hemagglutinin Cleavage Site in Highly Pathogenic Avian Influenza Genesis. Viruses. 2022 Jun 21;14(7). doi: 10.3390/v14071352. PMID: 35891333, PMCID: PMC9316147.
• De Bruin ACM, Spronken MI, Bestebroer TM, Fouchier RAM, Richard M. Reduced Replication of Highly Pathogenic Avian Influenza Virus in Duck Endothelial Cells Compared to Chicken Endothelial Cells Is Associated with Stronger Antiviral Responses. De Bruin ACM, Spronken MI, Bestebroer TM, Fouchier RAM, Richard M. Viruses. 2022 Jan 17;14(1), 165. doi: 10.3390/v14010165. PMID: 35062369, PMCID: PMC8779112. Corresponding author.
• de Bruin ACM, Funk M, Spronken MI, Gultyaev AP, Fouchier RAM, Richard M. Hemagglutinin Subtype Specificity and Mechanisms of Highly Pathogenic Avian Influenza Virus Genesis. Viruses. 2022 Jul 19;14(7):1566. doi: 10.3390/v14071566.
• Gultyaev AP, Spronken MI, Funk M, Fouchier RAM, Richard M. Insertions of codons encoding basic amino acids in H7 hemagglutinins of influenza viruses occur by recombination with RNA at hotspots near snoRNA binding sites. RNA. 2020 Nov 13:rna.077495.120. doi: 10.1261/rna.077495.120. PMID: 33188057.
• Gultyaev AP, Richard M, Spronken MI, Olsthoorn RCL, Fouchier RAM. Conserved structural RNA domains in regions coding for cleavage site motifs in hemagglutinin genes of influenza viruses. Virus Evolution. 2019 Aug 21;5(2):vez034. doi: 10.1093/ve/vez034. eCollection 2019 Jul. PMID: 31456885, PMCID: PMC6704317.

Antigenic evolution of avian influenza viruses and vaccine design

Dr. Richard’s team is working on understanding the antigenic evolution of avian influenza viruses and the molecular basis thereof, with a particular focus on the two main antigens of the virus, the hemagglutinin and the neuraminidase. This work paves the way to design broadly reactive vaccines against H5 and H7 avian influenza viruses, that have caused recent zoonoses, by designing antigenically central hemagglutinin and neuraminidase antigens.

• Kok A, Scheuer R, Bestebroer TM, Burke DF, Wilks SH, Spronken MI, de Meulder D, Lexmond P, Pronk M, Smith DJ, Herfst S, Fouchier RAM, Richard M. Characterization of A/H7 influenza virus global antigenic diversity and key determinants in the hemagglutinin globular head mediating A/H7N9 antigenic evolution. mBio. 2023 Aug 11:e0048823. doi: 10.1128/mbio.00488-23.
• Kok A, Fouchier RAM, Richard M. Cross-Reactivity conferred by homologous and heterologous prime-boost A/H5 influenza vaccination strategies in Humans: a literature review. Vaccines. 2021 Dec 10;9(12):1465.

Risk assessment of zoonotic respiratory viruses and genetic and phenotypic requirements of pandemic potential.

In 2013, the H7N9 virus emerged in China, causing human cases of infection. Early in the outbreak, it was critical to understand the potential for this virus to transmit via the airborne route, as this is the major route of influenza virus transmission between humans. Dr. Richard demonstrated that the zoonotic H7N9 virus was transmissible via the airborne route, highlighting this virus as a pandemic threat. To really understand the potential impact of H7N9 viruses on public health, she subsequently investigated markers that influence phenotypes important for airborne transmission. Dr. Richard has also characterized several other emerging zoonotic influenza viruses to assess whether these would represent a pandemic risk for the human population. This line of work not only provided risk assessment of zoonotic influenza viruses, but also supported fundamental understanding of the genetic and phenotypic requirements for zoonotic influenza viruses to become pandemic. When SARS-CoV-2 sparked the current pandemic of COVID-19 in spring 2020, Dr. Richard used her expertise on transmission of influenza viruses to understand the modes of transmission of this newly emerging virus. This work has made a tremendous impact on the coronavirus field, as this is one of the first studies demonstrating that SARS-CoV-2 is transmissible between ferrets not only via contact, but also via respiratory droplets and/or aerosols.

• Kutter JS, de Meulder D, Bestebroer TM, Lexmond P, Mulders A, Richard M, Fouchier RAM, Herfst S. SARS-CoV and SARS-CoV-2 are transmitted through the air between ferrets over more than one meter distance. Nature Communications. 2021 Mar 12;12(1):1653. PMID: 33712573.
• Richard M, Kok A, de Meulder D, Besterbroer TM, Lamers MM, Okba NMA, Fentener van Vlissingen M, Rockx B, Haagmans BL, Koopmans MPG, Fouchier RAM, Herfst S. SARS-CoV-2 is transmitted via contact and via the air between ferrets. Nature Communications. 2020 Jul 8;11(1):3496. PMID: 32641684, PMCID: PMC7343828.
• Herfst S, Mok CKP, van den Brand JMA, van der Vliet S, Rosu ME, Spronken MI, Yang Z, de Meulder D, Lexmond P, Bestebroer TM, Peiris JSM, Fouchier RAM, Richard M. Human Clade 2.3.4.4 A/H5N6 Influenza Virus Lacks Mammalian Adaptation Markers and Does Not Transmit via the Airborne Route between Ferrets. mSphere. 2018 Jan 3;3. PMID: 29299528, PMCID: PMC5750386. Corresponding author.
• Richard M, Herfst S, van den Brand JMA, de Meulder D, Lexmond P, Bestebroer TM, Fouchier RAM. Mutations Driving Airborne Transmission of A/H5N1 Virus in Mammals Cause Substantial Attenuation in Chickens only when combined. Scientific Reports. 2017 Aug 3;7(1):7187. PMID: 28775271, PMCID: PMC5543172. Corresponding author.
• Richard M*, Schrauwen EJ*, Burke DF, Rimmelzwaan GF, Herfst S, Fouchier RA. Amino acid substitutions that affect receptor binding and stability of the hemagglutinin of influenza A/H7N9 virus. Journal of Virology. 2016 Jan 20;90(7):3794-9. PMID: 26792744, PMCID: PMC4794686. Corresponding author.
• Richard M, Herfst S, van den Brand JM, Lexmond P, Bestebroer TM, Rimmelzwaan GF, Koopmans M, Kuiken T, Fouchier RA. Low Virulence and Lack of Airborne Transmission of the Dutch Highly Pathogenic Avian Influenza Virus H5N8 in Ferrets. PLoS One. 2015 Jun 19;10(6):e0129827. PMID: 26090682, PMCID: PMC4474857. Corresponding author.
• Richard M and Fouchier RA. H10N8 and H6N1 Maintain Avian Receptor Binding. Cell host and Microbes. 2015. Mar 11;17(3):292-4. PMID: 25766290.
• Richard M*, Schrauwen EJ*, de Graaf M, Bestebroer TM, Spronken MI, van Boheemen S, de Meulder D, Lexmond P, Linster M, Herfst S, Smith DJ, van den Brand JM, Burke DF, Kuiken T, Rimmelzwaan GF, Osterhaus AD, Fouchier RA. Limited airborne transmission of H7N9 influenza A virus between ferrets. Nature. 2013 Sep 26;501(7468):560-3. (*equal contribution). PMID: 23925116, PMCID: PMC3819191.

Fundamental understanding of influenza virus transmission and reassortment

Dr. Richard has worked in collaboration with Dr. Sander Herfst (Viroscience Department, ErasmusMC, with Dr. Lowen (Emory University, US), who studies reassortment of influenza viruses using genetically tagged viruses. They thought of novel uses for these tagged viruses: understanding how viral tropism would restrict reassortment and understanding where in the respiratory tract influenza viruses are generated for transmission. Together, they showed that replication in two different anatomical sites in the respiratory tract restricts reassortment of influenza viruses. They also showed that influenza viruses are expelled from the upper respiratory tract for onwards transmission and highlight the nasal cavity as the source of transmissible viruses.

• Richard M, van den Brand JMA, Bestebroer TM, Lexmond P, de Meulder D, Fouchier RAM, Lowen AC, Herfst S. Influenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets. Nature Communications. 2020 Feb 7;11(1):766. PMID: 32034144, PMCID: PMC7005743.
• Richard M, Herfst S, Tao H, Jacobs NT, Lowen AC. Influenza A virus reassortment is limited by anatomical compartmentalization following co-infection via distinct routes. Journal of Virology. 2018 Mar;92-5. PMID: 29212934, PMCID: PMC5809721.

For a complete list of publications, see: 

• Link to ORCID
• Link to NCBI
• Link to web of science

Managing, development & organization

2021 - present: Management team Infection and Immunity (I&I) Master | Erasmus MC, Rotterdam | the Netherlands

2021 - present: Organizer of a two-yearly Virology Course for PhD-students organizer | 1,5 ECTS | ~70 participants

2015 - 2018: Organizer of the Postgraduate School Molecular Medicine Course | Erasmus MC, Rotterdam | the Netherlands

Lecturing

2022: EpiViral Summer School | Invited lecture | Aveiro | Portugal

2022 - present: Master Biology | Frontiers in Biology | Yearly invited lecture | Wageningen University | the Netherlands

2021 - present: Master Infectiology | Advances in Virology | Yearly invited lecture | University Claude Bernard Lyon 1 | France

2018 - present: Biomedical research in Practice (BRiP) | Medicine Bachelor Minor | Erasmus MC, Rotterdam | the Netherlands

2016 - present: Master programme Infection and Immunity (I&I) | Two-yearly lectures | Erasmus MC, Rotterdam | the Netherlands.

2015 - 2018: Postgraduate School Molecular Medicine Course | Yearly lecture | Erasmus MC, Rotterdam | the Netherlands

2015 - 2017: Micro & Immunobiology Bachelor | Yearly invited lecture | Erasmus University College, Rotterdam | the Netherland

2015: Technical Forum | Radboud Institute for Molecular Life Sciences (RIMLS) | Nijmegen | the Netherlands

2007 - 2010: Bachelor | Biochemistry, Histology, Cellular Biology, Microbiology | Institut Universitaire Technique A | University Claude Bernard Lyon 1 | France

Outreach activities

Selected Invited Lectures

2023: Emergence of highly pathogenic avian influenza viruses | Coordonated Actions | French Research Council (ARNS) | Paris | France

2023: Avian influenza viruses: how to cope with antigenic diversity for prepandemic prepardness and vaccine design? | Vaccinology Masterclass | Almere | the Netherlands

2023: Antigenic Cartography | ESFLU workshop | Royal GD | Deventer | the Netherlands

2021: H5 avian influenza virus antigenic evolution and challenges for vaccine design | Keynote | Vaccine Symposium | Utrecht Molecular Immunology Hub (UMI) | Online

2018: Highly Pathogenic Avian Influenza H5N1 viruses. Evolution, Transmission and Genesis | Department of Pathology | Cambridge University | UK

2017: Highly Pathogenic Avian Influenza H5N1 viruses. Evolution, Transmission and Genesis | International Center for Infectiology Research | Lyon | France

2016: The newly emerged reassortant viruses of the influenza H5 A/Goose/Guangdong/1/96 lineage | Satellite Symposium | 6th European Congress of Virology | Hamburg | Germany

2016: Characterization of highly pathogenic avian influenza H5N6 virus of clade 2.3.4.4 | Keynote | 10th Vaccine Congress | Amsterdam | the Netherlands

Other positions

Editorial boards

2022 - present: Guest Editor of PLOS Pathogens

2021 - present: Associate Editor of Frontiers in Virology | Viral Disease Investigation

2021 - present: Academic Editor of Microbiology Spectrum | Section Virology

2021: Guest Editor of Viruses Special topic | Highly pathogenic avian influenza virus emergence

2020 - present: Topic Editor of Viruses

2018: Guest Editor of Frontiers in Microbiology Special topic | RNA virus polymerases: forming bonds and balancing errors

2018 - present: Academic Editor PLOS One

Review panel member

2022 - present: Committee PhD Defenses | Dilweg (2022), Lamers (2022), Wolff (2022), Rijsbergen (2023), Filaire (2023)

2011 - present: Frequent reviewer for top journals in the field | Nature, Nature Microbiology, Nature communications, PLOS Pathogens, Cell Host&Microbe, Cell reports, elife, mBio, Journal of Virology (non-exhaustive list)

2023 - 2025: Member International Scientific Evaluation Committee Priority Research and Equipment Program Emerging and Infectious Diseases | PEPR MIE | French Research Council (ARNS)

2023: Evaluation Committee Dutch Research Council (NWO) | Veni program

2023: Reviewer for the Max Plank Institute | Kouba Dioscuri program

2023: Reviewer for ISIDORe | Integrated Services for Infectious Disease Outbreak Research

2020: Reviewer for the French National Research Council|2019Reviewer for the Polish National Research Council

Organisation of scientific meetings

2018: 8th Orthomyxovirus Research Conference | Hanoi | Vietnam

2018: 1rst Dutch Replication Meeting | Delft | the Netherlands

2016: International expert workshop on pathogen inter- and intraspecies transmission | the Netherlands

External consultancies

2015: European Food Safety Agency (EFSA) on the mechanisms and risk factors for the transition from LPAIV to HPAIV

Institutional responsibilities

2022 – present: Member of the National Influenza Center

2022 – present: Supervisor of the Intervision PhD program, Erasmus MC

2021 - present: Core teacher of the Infection and Immunity (I&I) Master, ErasmusMC

2015 - present: PI and co-PI on several approved Centrale Commissie Dierproven (CCD) project licences

2015 - 2021: Coordination of BARDA contract

2014 - 2016: Coordination of NIH/NIAID CEIRS contract

Current

2023-2025: NIH/NIAID Centers of Excellence on Influenza Research and Response (CEIRR) | Pilot project | PI | USD 507.000: The role of small nucleolar RNAs in nonhomologous recombination between influenza virus genes or with exogenous RNA

2023-2028: NIH/NIAID R01 | PI | USD 1.830.000: Unravelling highly pathogenic influenza virus emergence

2022-2026: Dutch Research council (NWO-ENW) | M1 grant | PI | EUR 364.496: INFLUENCE: Unravelling highly pathogenic influenza virus emergence

2022-2027: EU4Health program | co-PI (consortium) | EUR 1.549.903: Delivering a Unified Research Alliance of Biomedical and Public Health Laboratories against Epidemics (DURABLE)

2023-2028: EU Horizon 2020 program | co-PI (consortium) | EUR 1.093.750: Kappa-Flu: Understanding the connectivity and dynamics of avian influenza in wild birds, poultry and the environment

2022-2027: NIH/NIAID R01 | Co-investigator | USD 763.473: Integrating measurements of immune escape and in vitro replication with computational models to understand and predict the antigenic evolution of seasonal A/H3N2 influenza viruses

2021-2028: NIH/NIAID CEIRR | Base contract | co-PI | USD 1.200.000: Molecular determinants of viral emergence, virulence, evolution and transmission

Past

2017-2022: EU Horizon 2020 program | PI (consortium) | EUR 539.750: Delta-Flu: Dynamics of avian influenza in a changing world

2018-2021: NIH/NIAID Center of Excellence on Influenza Research and Surveillance (CEIRS) | Pilot project | PI | USD 400.000: Genesis and pathogenesis of highly pathogenic avian influenza A viruses in avian species

2015-2021: Biomedical Advanced Research Development Authority (BARDA) | co-PI | USD 1.650.420: Advanced vaccination and immunity management strategies to protect from influenza virus infection

2016-2021: NIH/NIAID CEIRS | Surveillance core project | co-PI | USD 436.168: Development and assessment of antigenically advanced candidate vaccine viruses for seasonal human influenza

2016-2021: NIH/NIAID CEIRS | Emerging pathogen project | co-PI | USD 328.700: Tracing the antigenic evolution of H5 hemagglutinins using antigenic cartography

2017-2019: NIH/NIAID CEIRS | Immune response project | co-PI | USD 290.000: Peripheral blood mononuclear cells analyses of the hemagglutinin-specific B cell repertoire

2014-2021: NIH/NIAID CEIRS | Base contract | co-PI | USD 3.516.509: Hemagglutinin determinants of virus phenotype: antigenicity, virulence, and transmission

2011: NIH/NIAID CEIRS | Pilot Project | co-PI | USD 300.000

2012: EUR Fellowship | EUR 7.000

2007-2010: PhD Fellowship | French Ministry of Education and Research | top 5% | EUR 60.000

Active

• Dr. Seema Lakdawala | Protein-RNA interactions in influenza viruses | Emory University | USA
• Dr. Aartjan te Velthuis | Influenza virus polymerase replication and transcription | Princeton University | USA
• Dr. David Bauer | RNA structure probing in influenza virus genome | Francis Crick Institute | UK
• Dr. El-Sayed El-Whab | Highly pathogenic avian influenza viruses tropism | Friedrich-Loeffler-Institute, |Germany
• Dr. Robert de Vries & Prof. Geert-Jan Boons | Influenza virus receptor binding | Utrecht University | The Netherlands
• Prof. Derek Smith | Antigenic evolution of influenza viruses | University of Cambridge | UK
• Prof. Yoshiro Kawaoka & Dr. Gabriele Neumann | Antigenic evolution of influenza viruses | University of Winsconsin | USA

Past

• Dr. Anice Lowen | Reassortment of influenza virus | Emory University of School of Medicine | USA
• Dr. Sascha Trapp | Development of avian cell culture systems | University of Tours | France
• Prof. Nynke Dekker | Single molecule studies of RNA dependent RNA polymerases | Delft University of Technology | the Netherlands
• Dr. Chris Mok | Risk assessment of emerging zoonotic avian influenza A viruses | Hong-Kong University Pasteur Research Pole | China
• Dr. Kirsty Short | Interactions between lung epithelial and endothelial cells | Brisbane University | Australia

Group of dr. Richard

Current members

Monique Spronken | PhD Student | 2023 - present
Willemijn Rijnink | PhD student | 2021 - present
Adinda Kok | PhD student | 2017 - 2024
Anja de Bruin | PhD student | 2017 - 2024
Mathis Funk| Post-doc | 2018 - present
Theo Bestebroer | Technician | 0.5 FTE
Mark Pronk | Technician | 0.5 FTE
To be hired | 1 PhD student, 1 junior post-doc, 1 technician

Former members

PhD Students | Victor Lorente Leal
MSc Students | Rik Ruijten, Evelin Valjaots, Lieke de Jong, Raissa Davis, Geunho Choi, Anne Reiners
BSc Students | Sivana Baptista Varela, Lars van den Biggelaar, Rik Bouwels, Romy van Acker, Jocynthe Buzink
Technicians | Rachel Scheur, Djenolan van Mourik, Stefan van der Vliet