Menno C. van Zelm, PhD

Research overview

B cells are a critical component of the human immune system, producing antibodies to combat infection and long-lived memory cells to protect against disease upon secondary infection, often for life. However, abnormalities in B cell development or function can lead to immunodeficiency, autoimmunity and allergic diseases. The outcomes of immunization and treatment of immune-mediated diseases are unpredictable, largely inefficient and empirical, posing a large societal burden via life-long therapy and infection susceptibility. Molecular insights into the pathways underlying the formation, durability and plasticity of immune memory are needed to overcome the limitations in current intervention strategies.

Research aims

In the past 8 years at Monash University in Melbourne, Australia, our group has developed, patented and applied new technologies to ex vivo evaluate antigen-specific, human B-cell memory following infection, vaccination and treatment intervention. Between the two sister laboratories at Monash University (Allergy and Clinical Immunology; ACI) and Erasmus MC (Humoral Immune Memory; HUM), we will apply these new technologies for quantitative measurements of immune memory and thereby systematize the provision and use of an evidence base for clinical care and assessing vaccination strategies.

Current Research

Current research lines include:

1. Defining the contribution of rare and common genetic variants to the severity and heterogeneity of disease in patients with predominantly antibody deficiency
   ACI team; collaboration with PID
2. The impact of early-life exposures such as persistent viral infections, intestinal microbiota, stress, Vitamins D T-cell and B-cell memory, and their risk for developing immune-mediated diseases (esp. Celiac disease and allergies)
   HUM team in collaboration with the Generation R Study
3. Abnormal IgE responses and memory B cells in allergic asthma and anaphylaxis, and how IgG induced by allergen-specific immunotherapy inhibits IgE-mediated effector cell activation.
   HUM and ACI teams
4. Diversity, specificity and durability of B-cell memory following vaccination or natural infection with zoonotic viruses (influenza, SARS-CoV-2)
   HUM and ACI teams

Major achievements in the past years

1. Dissecting stepwise differentiation of precursor-B cells in bone marrow, the regulation of Ig gene rearrangements including the roles of IL7R signaling and ID2 (J Immunol 2005;175:5912-5922; Cell 2008;133:265-79; Cell 2009;238:435-448; Blood 2011;118:2116-2127; J Immunol 2013;191:1210-1219; Nucleic Acids Res 2016;44(1):175-86; Sci Rep. 2016;6:33924).
2. Elucidating the genetic and immunological bases of primary antibody deficiencies (N Engl J Med 2006;354:1901-1912, J Clin Invest 2010;120:1265-1274, Front Immunol. 2019;10:768, Front Immunol. 2019;10:2593, J Allergy Clin Immunol. 2023)
3. Unraveling the origin of diverse human memory B cell subsets from T-cell independent, T-cell dependent, and recurrent immune responses (J Exp Med 2007; 204:645-655; Blood 2011;118:2150-8; J Allergy Clin Immunol. 2014; 34(3):688-697.e6; J Immunol 2015;195(4):1417-26; Immunol Cell Biol. 2017;95(9):744-752; J Immunol. 2018;201(7):1928-1935).
4. Showing dysregulation of B-cell memory in allergy, and how this is affected by treatment (J Allergy Clin Immunol. 2014;134(6):1346-1353.e9; Allergy. 2018;73(6):1331-1336; Allergy. 2020;75(5):1121-1132; Allergy. 2021 76(10):3028-3040; Allergy. 2023 78(3):822-835)
5. Shaping of adaptive immunity in young children by non-genetic factors (J Infect Dis. 2016;213(2):233-42; J Pediatr. 2016;170:126-134; J Leukoc Biol. 2017;101(4):949-956; J Allergy Clin Immunol. 2017;139(6):1923-1934)
6. Detailed examination of immune memory and its durability following natural infection and vaccination (Clin Transl Immunology. 2020;9(10):e1199; Sci Immunol. 2020;5(54):eabf8891; Allergy. 2023 78(3):855-858; J Clin Immunol. 2023 Jun 16)

(See all publications for Menno van Zelm in Pubmed)

HUM Group members

• Menno C. van Zelm, Principal Investigator
• Magdalena A. Berkowska, Postdoctoral Scientist
• Sara Kassem, Research Assistant

ACI team at Monash University

Research Fellows

• Dr Emily Edwards
• Dr Anouk von Borstel
• Dr Paul Gill

Project Officer

• Dr Bernadette Jones-Freeman (Senior Project Manager – PROPHECY Study)

Research Assistants

• Ms Pei Mun Aui
• Dr Simone Reinwald
• Ms Holly Fryer
• Ms Alina Wang

PhD students

• Ms Gemma Hartley
• Ms Lin (Kathy) Hsin
• Ms Ebony Blight
• Mr Jack Edwards

Alumni

• Ms Kathya Fernando
  Research assistant 2022-2023
• Ms Shir Sun
  Research assistant 2022-2023
• Ms Nirupama (Neeru) Varese
  Research assistant (for many years until 2022)
• Dr Kirsten Looman: MD, PhD
  PhD thesis: “The early life adaptive immunity: Determinants and immune-mediated diseases” (2015-2022)
• Dr Craig I. McKenzie, PhD
  Postdoc 2017-2021
• Dr Paul A. Gill, PhD
  PhD thesis: “Investigating Immune Effects of Short-Chain Fatty Acids in Healthy Humans” (2016-2020)
• Ms Eliza Watson
  Research Assistant 2017-2019
• Dr Jorn J. Heeringa, MD, PhD
  PhD thesis: “The B-cell side of Allergy and Chronic Inflammatory Disease: Studies on the source of IgE and IgG4” (2012-2018)
• Dr W.M. (Marieke) Timmermans, MD, PhD
  PhD thesis: “Immunopathogenesis of Granulomas in Chronic Inflammatory Diseases: Relevance to diagnostics, biomarkers and treatment” (2013-2018)
• Dr Michelle A.E. Jansen, MD, PhD
  PhD thesis: “Shaping of Adaptive Immunity and Celiac Disease Autoimmunity in a Population based Childhood Cohort: The Generation R Study” (2010-2017)
• Dr Gavin Brooks, PhD
  Postdoc 2016
• Dr Lieke S.J. Kamphuis, PhD
  PhD thesis: “The Many Faces of Sarcoidosis Novel insights into pathogenesis, diagnostics and therapy” (2009-2016)
• Dr Magdalena B. Rother, PhD
  PhD thesis: “Formation of the Immunoglobulin Repertoire in Precursor-B-cell Development” (2010-2015)
• Dr Diana van den Heuvel, PhD
  PhD thesis: “The Immune System out of Shape? Shaping of adaptive immunity by persistent viral infections in young children” (2010-2015)
• Dr Ruud H.J. Verstegen, MD, PhD
  PhD thesis: “Humoral Immunity in Children with Down Syndrome: relevance to respiratory disease” (2015)
• Dr Magdalena A. Berkowska, PhD
  PhD thesis: “Generation of an immunocompetent B-cell repertoire” (2008-2012)
• Dr Katharina Nothelfer, PhD
  Postdoc 2014-2015
• Benjamin Bartol, BSc
  Technician 2008-2015
• Halima Charif, BSc
  Technician 2011-2014
• Kevin A.M. van Kester, BSc
  Technician 2012
• Edwin F.E. de Haas, BSc
  Technician 2008-2011

Hons and MSc students

• Holly Fryer, 2022
• Liam Ta, 2022
• Ebony Blight 2021
• Sabina Masinovic 2020
• Charlotte Leijten 2019-2020
• Gemma Hartley 2019
• Rosalyn Cao 2018
• Adam Nelson 2018
• Tarnia Fischer 2018
• Janice Klingenberg 2018
• Floor Vissers 2018
• Samuel de Jong 2016
• Eliza Watson 2016
• Fatemeh Ahmadi 2015
• Liza Rijvers 2013-2014
• Kyra Smit 2013-2014
• Hessel van der Weide 2013
• Sanne van de Bovenkamp 2012-2013
• Ingrid Snijdewind 2011-2012

BSc students

• Nicole Borggreven 2015
• Lemelinda Marques 2014-2015
• Jasper Rip 2014
• Roel Kroek 2013-2014
• Rachid Bouzid 2013-2014
• Marleen Hoozemans 2012-2013
• Dan Zhao 2012-2013
• Michael Vermeulen 2009-2010
• Abdullah Tarique 2010