About M. (Mieke) Metzemaekers, MSc, PhD
Description of research line
Our current research aims to dissect a cornerstone of our adaptive immune system: the capacity of memory T cells to rapidly ‘recall’ their effector program in order to provide durable protection against tumors and previously encountered pathogens. We employ state-of-the art immunological, (epi)genomics and computational approaches to unravel the molecular mechanisms that underpin immunological memory in primary human memory T cells from blood and lung tissue. These efforts will ultimately facilitate the identification of gene regulatory networks that can be targeted in human diseases in which dysfunctional memory T cells play a pivotal role (e.g. allergy, autoimmunity and cancer).
Education and career
Mieke Metzemaekers obtained her BSc, MSc and PhD degrees in Biomedical Sciences at KU Leuven in Belgium. During her PhD, she studied the role of neutrophils and inflammatory proteins in autoimmunity, auto-inflammation and COVID-19 in the laboratory of Prof. Paul Proost. These experiences left her with a deep desire to dissect the molecular mechanisms that regulate the identity and function of immune cells in her future career. In November 2021, Mieke joined the group of Dr. Ralph Stadhouders at Erasmus MC to start postdoctoral research on the epigenetic basis of immunological memory in human T cells.
Selected publications
De Langhe E, Van Loo S*, Malengier-Devlies B*, Metzemaekers M*, Staels F*, Vandenhaute J*, Berghen N, Sciot R, Corveleyn A, Tšuiko O, Gouwy M, Lenaerts JL, Verschueren P, Wouters C, Proost P, Matthys P, Legius E, Schrijvers R. TET2-driver and NLRC4-passenger variants in adult-onset autoinflammation. N Engl J Med. 2023 388:1626-1629.
Rodenburg LW, Metzemaekers M, van der Windt IS, Smits SMA, den Hertog-Oosterhoff LA, Kruisselbrink E, Brunsveld JE, Michel S, de Winter-de Groot KM, van der Ent CK, Stadhouders R, Beekman JM, Amatngalim GD. Exploring intrinsic variability between cultured nasal and bronchial epithelia in cystic fibrosis. Sci Rep. 2023 13:18573.
Metzemaekers M, Malengier-Devlies B, Yu K, Vandendriessche S, Yserbyt J, Matthys P, De Somer L, Wouters C, Proost P. Synovial fluid neutrophils from patients with juvenile idiopathic arthritis display a hyperactivated phenotype. Arthritis Rheumatol. 2021 73:875-884.
Metzemaekers M*, Mortier A*, Vacchini A, Boff D, Yu K, Janssens R, Farina FM, Milanesi S, Berghmans N, Pörtner N, Van Damme J, Allegretti M, Teixeira MM, Locati M, Borroni EM, Amaral FA, Proost P. Endogenous modification of the chemoattractant CXCL5 alters receptor usage and enhances its activity toward neutrophils and monocytes. Sci Signal. 2021 14:eaax3053. *Joint first authors.
Metzemaekers M*, Cambier S*, Blanter M, Vandooren J, de Carvalho AC, Malengier-Devlies B, Vanderbeke L, Jacobs C, Coenen S, Martens E, Pörtner N, Vanbrabant L, Van Mol P, Van Herck Y, Van Aerde N, Hermans G, Gunst J, Borin A, Toledo N Pereira B, Dos Sp Gomes AB, Primon Muraro S, Fabiano de Souza G, S Farias A, Proenca-Modena JL, R Vinolo MA, the CONTAGIOUS Consortium, Marques PE, Wouters C, Wauters E, Struyf S, Matthys P, Opdenakker G, Marques RE, Wauters J, Gouwy M, Proost P. Kinetics of peripheral blood neutrophils in severe coronavirus disease 2019. Clin Transl Immunology. 2021 10:e1271. *Joint first authors.
Metzemaekers M, Abouelasrar Salama S, Vandooren J, Mortier A, Janssens R, Vandendriessche S, Ganseman E, Martens E, Gouwy M, Neerinckx B, Verschueren P, De Somer L, Wouters C, Struyf S, Opdenakker G, Van Damme J, Proost P. From ELISA to immunosorbent tandem mass spectrometry proteoform analysis: the example of CXCL8/interleukin-8. Front Immunol. 2021 12:644725.
*Joint first authors.
Other positions
- Chair of the Young Investigator Board of the Netherlands Respiratory Society (NRS)
- Member of the NRS News Committee
Recent findings
Neutrophils are protagonists of innate immunity and represent the most prevalent immune cells in human blood. While adequate neutrophil activation is vital for pathogen elimination, excessive neutrophil responses causing collateral damage are a common feature of immunological diseases. To safeguard optimal host protection, a family of professional guidance proteins (or ‘chemokines’) tightly regulates neutrophil trafficking and activation. During her PhD, Mieke studied the role of neutrophils and chemokines in patients with autoimmune and auto-inflammatory arthritic disorders as well as COVID-19. This work has produced the following main scientific achievements:
- Novel insights on how neutrophils are endowed with unexpected plasticity at the RNA and protein level.
- Identification of activated neutrophil populations with altered potential for pro-inflammatory activities in distinct patient cohorts.
- Revealing how post-translational modifications control the activity of neutrophil-attracting chemokines to monitor immune responses.
- Development of tandem mass spectrometry-based methodology for differential quantification of authentic and post-translationally modified chemokines in clinical samples.
- Identification of hyper activated neutrophils and posttranslationally processed chemokines as potential drivers of chronic joint inflammation in rheumatic diseases.
