foto

I. Jongerius PhD

Positions
Associate Professor, Research Associate
Main activities
Education, Research
Specialisation
Complement Research, Immunology
Focus of research

Research lines

Characterization of alternative complement pathway regulator Factor H and Factor H related proteins

Factor H (FH) is an abundant plasma glycoprotein, and is the main regulator of the alternative complement pathway. FH serves as a cofactor for Factor I (FI) in the inactivation of C3b to iC3b and has decay-accelerating activity towards C3 convertases. FH binds to host cell surfaces, by binding to host specific glycosaminoglycans (GAGs) on the cell surface following initial complement activation and targets C3b to inhibit further complement activation. Dysfunctional FH may lead to severe inflammatory disease due to uncontrolled complement activation on the endothelial cells of the vasculature. As the major inhibitor of the alternative pathway of complement, FH may potentially be used as therapeutic agent for several complement mediated human diseases.

We have developed a purification strategy to isolate functional FH from human plasma. In addition, in close collaboration with Prof. T.W. Kuijpers (AMC-UMC) and Dr. T. Rispens (Sansquin) we have developed several antibodies against FH and Factor H Related proteins (FHRs). We investigate FH and FHRs levels and function in health and disease. In addition, we have developed a novel specific monoclonal antibody that potentiates the function of FH on human cell surfaces.

Complement activation and regulation on red blood cells

All healthy human cells are equipped with several surface complement regulators to prevent damage through unwanted complement activation. Endothelial cells and blood cells are particularly well protected, as these are constantly exposed to the complement system in plasma. Red blood cells (RBCs) bear all membrane complement regulators, except CD46, which is only expressed on nucleated cells

Various diseases are associated with complement mediated RBC destruction, which may be antibody mediated (autoimmune hemolytic anemia (AIHA), allo-immunization) or the result of defective complement regulation (atypical hemolytic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH)). Disease severity and response to existing complement inhibiting therapeutics is variable in these patients. This illustrates the urgent need to better understand both the triggering mechanisms of complement activation in these diseases and how the balance of complement activation and regulation on different cell surfaces is maintained.

We are investigating how RBCs are protected from unwanted complement activation, both in normal and pathological conditions, e.g. in AIHA and PNH. To answer our research questions we make use of a human cell line (HAP1) that is genetically engineered by CRISPR/Cas9 technology to lose one or several complement regulators (collaboration with Dr. R. Spaapen, Sanquin). Furthermore, we use isolated RBCs from healthy donors and PNH patients and plasma samples of AIHA patients.

Key publications
  • Baas Inge, Delvasto-Nuñez Laura, Ligthart Peter, Brouwer Conny, Folman Claudia, Reis Edimara S., Ricklin Daniel, Lambris John D., Wouters Diana, de Haas Masja, Jongerius Ilse, Zeerleder Sacha S. Complement C3 inhibition by compstatin Cp40 prevents intra- and extravascular hemolysis of red blood cells Haematologica 2020;105 (2):e57-e60 [PubMed]
  • Hovingh Elise S., van den Broek Bryan, Kuipers Betsy, Pinelli Elena, Rooijakkers Suzan H. M., Jongerius Ilse Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface PLoS pathogens 2017;13 (7) [PubMed]
  • Hovingh Elise S., de Maat Steven, Cloherty Alexandra P. M., Johnson Steven, Pinelli Elena, Maas Coen, Jongerius Ilse Virulence associated gene 8 of Bordetella pertussis enhances contact system activity by inhibiting the regulatory function of complement regulator C1 inhibitor Frontiers in immunology 2018;9 (JUN) [PubMed]
  • Jongerius Ilse, Lavender Hayley, Tan Lionel, Ruivo Nicola, Exley Rachel M, Caesar Joseph J E, Lea Susan M, Johnson Steven, Tang Christoph M Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor h binding protein PLoS pathogens 2013;9 (8):e1003528 [PubMed]
  • Ko Ya-Ping, Kuipers Annemarie, Freitag Claudia M, Jongerius Ilse, Medina Eva, van Rooijen Willemien J, Spaan András N, van Kessel Kok P M, Höök Magnus, Rooijakkers Suzan H M Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface PLoS pathogens 2013;9 (12):e1003816 [PubMed]
All Publications
Curriculum Vitae

Ilse Jongerius

Pr. Dr. W. Einthovenweg 3,

3731 KN de Bilt

0031(0)646955961

i.jongerius@sanquin.nl

 

Profile

An experienced and committed scientist, in the field of innate immunity, with specific focus on the complement system, and bacteriology who is purposefully efficient and likes a challenge. Planning, problem solving, coordinating and people management are my major skills. I have obtained several personal grants and have published in high impact, peer-reviewed international journals. I have an extensive international network due to my international experience and international collaborations.

Work experience

2018-present               Group Leader complement research, Sanquin research, Department of Immunopathology, NL

2014-2018                   Assistant professor (Veni laureate),  Department of Medical Microbiology, University Medical Center Utrecht (UMCU), NL

2013-2014                   Post-doctoral researcher, National Institute for Public Health and the Environment (RIVM), Center for Immunology of Infectious                                                    Diseases and Vaccines, NL

2010-2013                   Rubicon fellow, Sir Williman Dunn School of Pathology, Oxford University, UK; MCR Centre for Molecular Bacteriology and Infection,                                        Imperial College London, UK

My research focus and interest have always been “infection and immunity with emphasis on the complement system and bacterial evasion”. Today as group leader of the complement research at Sanquin my focus is shifting towards complement regulation of the human host. I have managed both my Veni and Rubicon projects and now supervising a group of 8 people consisting of a post doc, 3 PhD students and 4 technicians. My publication track record includes several first and last authorships in peer reviewed journals. I have obtained several prestigious personal  grants and presented my data on several (inter)national conferences. I have great pleasure in teaching students and have recently received my qualification to teach in higher eduction (BKO- basiskwalifikatie onderwijs). I am lecturer and workgroup leader, at several master courses and summer schools and tutor of several Biomedical students at the UMCU and AMC.

Co-promotor           Elise Hovingh, UU

                                    Unravalling the interactions between Bordetella pertussis and the innate immune system

                                 3 may 2018

                                 Anna van Beek, AMC

                                    Factor H family proteins in pediatric infectious diseases                   

                                    Date doctoral degree 27th of September 2019

                                 Laura Delvasto Nunez

                                Complement activation and neutrophil extracellular traps in de pathogenesis of thrombosis in autoimmune hemolytic anemia

                                Expected date doctoral degree 2021

                                Judith Zandstra

                                Identification and validation of new biomarkers to distinguish between bacterial or viral infection in children

                                Expected date doctoral degree 2021

 

Education

2005-2010                 PhD thesis “Complement evasion of Staphylococcus aureus Department of Medical Microbiology, UMCU, NL

2001-2005                Doctorate Biology, University Utrecht, NL

2000-2001                Propedeuse Biology, University Utrecht, NL

1994-2000                V.W.O.-atheneum, Minkema College, Woerden, NL 

 

Grants and awards

2018                           Contract research Gemini therapeutics (Co-Applicant 327.000,-)

2014                           VENI – NWO ZonMw (personal grant, 250.000,-)

2012                           Meningitidis UK – co-applicant (€190000,-)

2010                           NWO Rubicion – NWO ZonMw/ALW (personal grant, €147200,-)

2010                           EMBO Long-Term Fellowship – kindly declined (personal grant) 

2008                           International Complement Workshop travel award

2008                           Dutch “kiemprijs”: award for best first Medical Microbiology article of PhD students

2007                           DLA Science Meeting: award for best PhD abstract

2007                           American Society for Microbiology: Corporate Activities Program Student Travel Grant

 

Personal skills

BKO                         Basiskwalificatie onderwijs, teaching in higher education

Licenses                   Animal license (2011, UK), radiation protection (2008, NL)

Languages               Dutch (Native), English (excellent verbally and in writing)

Personal interest      Sports (gym, tennis and running), reading and like to participate in social events, spending time with my family

Character qualities  Social and contact capable, work in a team but also independent, resolute, efficient 

 

References:              Upon request

Publications

  • van Beek AE, Kamp A, Kruithof S, Nieuwenhuys EJ, Wouters D, Jongerius I, Rispens T, Kuijpers TW, Gelderman KA. Reference Intervals of Factor H and Factor H-Related Proteins in Healthy Children. Front Immunol. 2018 doi, 10.3389/fimmu.2018.01727.
  • Hovingh ES, Kuipers B, Bonačić Marinović AA, Jan Hamstra H, Hijdra D, Mughini Gras L, van Twillert I, Jongerius I, van Els CACM, Pinelli E. Detection of opsonizing antibodies directed against a recently circulating Bordetella pertussis strain in paired plasma samples from symptomatic and recovered pertussis patients. Sci Rep. 2018, doi, 10.1038/s41598-018-30558-8.
  • Hovingh ES, de Maat S, Cloherty APM, Johnson S, Pinelli E, Maas C, Jongerius I. Virulence Associated Gene 8 of Bordetella pertussis Enhances Contact System Activity by Inhibiting the Regulatory Function of Complement Regulator C1 Inhibitor. Front Immunol. 2018 doi: 10.3389/fimmu.2018.01172.
  • Hovingh ES, Mariman R, Solans L, Hijdra D, Hamstra HJ, Jongerius I, van Gent M, Mooi F, Locht C, Pinelli E. Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor. Emerg Microbes Infect. 2018, doi, 10.1038/s41426-018-0039-8.
  • Hollingshead S, Jongerius I, Exley RM, Johnson S, Lea SM, Tang CM. Structure-based design of chimeric antigens for multivalent protein vaccines. Nat Commun. 2018, doi,  10.1038/s41467-018-03146-7.
  • Hovingh, E.S., van den Broek, B., Pinelli, E., Kuipers, B., Rooijakkers, S.H.M., and Jongerius, I. Acquisition of C1 inhibitor by Bordetella pertussis virulence associated gene 8 results in C2 and C4 consumption away from the bacterial surface. Plos Pathogens. 2017,  doi, 10.1371/journal.ppat.1006531.
  • Hovingh E.S., van den Broek B, Jongerius I. Hijacking complement regulatory proteins for bacterial immune evasion. Front. Microbiol. 2016, doi: 10.3389/fmicb.2016.02004.
  • Jongerius I, Schuijt TJ, Mooi FR, Pinelli E. Complement evasion by Bordetella pertussis: implications for improving current vaccines. J Mol Med (Berl). 2015 Apr;93(4):395-402. doi: 10.1007/s00109-015-1259-1.
  • van der Veen, S., Johnson, S., Jongerius, I.,  Malik, T., De Jorge, E.G., Genovese, A., Santini, L., Staunton, D., Ufret-Vincenty, R., Pickering, M., Lea, S.M., and Tang, C.M. Non-Functional Variant 3 Factor H Binding Proteins as Meningococcal Vaccine Candidates. Infect. Immun. 2014;82(3):1157-63. doi: 10.1128/IAI.01183-13.
  • Ko. Y*., Kuipers A*., Freitag C.M*. Jongerius I*., Medina, E., van Rooijen, W.J., Spaan, A.N., van Kessel, K.P.M., Höök, M., and Rooijakkers, S.H.M. Phagocytosis escape by a Staphylococcus aureus protein that connects complement and coagulation proteins at the bacterial surface. PLoS Pathog. 2013, e1003816.
  • Amdahl, H., Jongerius, I., Meri, T., Pasanen, T., Hyvärinen, S., Haapasalo, K., van Strijp, J.A., Rooijakkers, S.H.M., and Jokiranta, T.S. Staphylococcal Ecb protein and host complement regulator factor H enhance functions of each other in bacterial immune evasion. J. Immunol., 2013, 191:1775-84.
  • Jongerius, I., Lavender, H., Tan, L., Ruivo, N., Exley, R.M., Caesar, J.J., Lea, S.M., Johnson, S., and Tang C.M. Distinct binding and immunogenic properties of the gonococcal homologue of meningococcal factor H binding protein. PLoS Pathog. 2013, 9(8):e1003528.
  • Jongerius, I*., von Köckritz-Blickwede, M*., Horsbrugh, M.J., Ruyken, M., Nizet, V., and Rooijakkers, S.H.M. Staphylococcus aureus virulence is enhanced by secreted factors that block innate immune defenses. J. Innate Immun., 2012, 4:301-311.
  • Stork, M., Bos, M.P., Jongerius, I., de Kok, N., Schilders, I., Weynants, V.E., Poolman., J.T., and Tommassen, J. An outer membrane receptor of Neisseria meningitidis involved in zinc acquisition with vaccine potential. PLoS Pathog. 2010, 6;e1000969.
  • Roussel-Jazédé, V., Jongerius, I., Bos, M.P., Tommassen, J., and van Ulsen, P. NalP-mediated proteolytic release of lactoferrin-binding protein B from the meningococcal cell surface. Infect. Immun., 2010, 78:3083-3089.
  • Jongerius, I., Ruyken, M., van Strijp, J.A.G., and Rooijakkers, S.H.M. Extracellular complement binding protein inhibits the formation of the catalytic subunits of convertases: C2a and Bb. J. Biol. Chem., 2010, 284:14973-14979.
  • Ten Broeke-Smits., N., Pronk, T., Jongerius, I., Bruning, O, Wittink, F., Breit, T., van Strijp, J.A.G., Fluit, A., and Boel, E. Operon Structure of Staphylococcus aureus. Nucl. Acids Res., 2010, 38:3263-3274.
  • Jongerius, I., Puister, M., Wu., J, Ruyken, M., van Strijp, J.A.G., and Rooijakkers, S.H.M. Immunomodulatory functions of convertase dimerization by S. aureus complement inhibitor. J.Immunol., 2010, 184:420-425.
  • Jongerius, I., Köhl, J., Pandey, M.K., Ruyken, M., van Kessel, K.P.M., van Strijp, J.A.G., and Rooijakkers, S.H.M. Staphylococcal complement evasion by various convertase-blocking molecules. J. Exp. Med., 2007, 204:2461-2471.

*authors contribute equally

Book chapters

Jongerius, I., Ram, S., and Rooijakkers, S.H.M. Bacterial complement escape. Chapter of: Pathogen-Derived Immunomodulatory Molecules. ISBN: 978-1-58706-334-3 publication date: august 15, 2009.

Patents

  • WO2014030003 (A1) NEISSERIA MENINGITIDIS FHBP VARIANT AND ITS USE FOR VACCINATION   
  • WO2014140562 (A1) IMMUNOGENIC COMPOSITION TO NEISSERIA  
  • GB1614687.0 MODIFIED FACTOR H BINDING PROTEIN (filed 31 August 2016).
Current PhD Candidates
  • E.C.W. de Boer
  • L.V. Delvasto Nunez
  • J. Zandstra