Chronic inflammation and blood-brain barrier disruption in neurodegeneration

Research towards treating neurodegenerative disorders, such as multiple sclerosis, is aimed at halting ongoing inflammation and restoring brain function, but the (environmental) trigger of disease is still unknown. Therefore, our team searches for the cause(s) of neurodegeneration, combining fundamental research on mechanisms of chronic inflammation and blood-brain barrier (BBB) disruption with the investigation of obesity as an inflammatory cause of neurodegeneration. In this way, novel therapeutic targets are identified and validated for use in patients.

Research lines:

1. Regulatory T cell stability in the inflamed central nervous system
   Investigating both the immune-suppressive and remyelinative capacity of Tregs in neuroinflammation and -degeneration with the focus on identifying therapeutic targets for MS.
2. Inflammasome activation
   Studying inflammasome activation, an atypical characteristics of T helper cells in MS, and how this contributes to disease progression.
3. Effect of lifestyle and diet on neuroinflammation
   Examining the role of adipose tissue-derived immune cells or extracellular vesicles in triggering neuroinflammation and identifying other dietary influences like high salt on BBB permeability.

• (Spectral) Flow cytometry and cell sorting: help with design and optimization, or use of validated immune phenotyping panels (including 14 to 30 colour panels). More information on the ‘Flow Cytometry Unit’ can be found here.
  
  
• In vitro and in vivo blood-brain barrier models: to study immune cell adhesion and migration, transport of compounds, activation and integrity of the BBB.
  
  
• Molecular and cellular tools to investigate T lymphocyte function, including Treg suppression, T cell proliferation, cytotoxicity etc.
  
  
• Bulk and single cell RNA sequencing: help with experimental design and work flow.
  
  
• In vivo models of multiple sclerosis, including clinical and pathological readouts.

Prof. dr. Bieke Broux: group leader

Bieke Broux (°1985), PhD, is Assistant   Professor Immunology and group leader   of the CBN team at Hasselt University   (Biomedical Research Institute). After her PhD, she obtained a postdoctoral fellowship grant from the Fund for   Scientific Research Flanders (FWO). During the first two years of this postdoctoral fellowship, she worked in the lab of Prof. Dr. Alexandre Prat (CRCHUM, Université de Montréal, Canada), on blood brain barrier biology and disruption in multiple sclerosis. For her return to BIOMED, she obtained a prestigious European ECTRIMS postdoctoral fellowship grant, as well as several bench fee grants (Belgian Charcot Foundation, FWO, Belgian MS support fund) to start a research line on the blood brain barrier in multiple sclerosis at the Biomedical Research Institute. In addition, she recently received a Global MS Research Booster Award, an international fellowship grant awarded once every two years by the Dutch “Stichting MS Research” to boost the development of a postdoctoral fellow into an independent group leader. Since 2021, she is appointed as Assistant Professor Immunology at Hasselt University.

Paulien Baeten: Postdoctoral fellow

Paulien Baeten (°1994) is a postdoctoral researcher in the CBN lab of Prof. Dr. Bieke Broux at Hasselt University (Biomedical Research Institute). After studying Biomedical Sciences at Hasselt University, she started as a FWO-SB PhD fellow in 2018. Her PhD project focused on regulatory T cells (Tregs) interacting with the inflamed blood-brain barrier in MS. After obtaining her PhD in 2022, she received a VLAIO postdoctoral innovation mandate to translate the results of her PhD towards clinical application. For this topic, she performed in vitro BBB modelling and human Treg assays (FACS, extended spectral flow cytometry, suppression assays, ...) and human Treg genome editing (CRISPR-Cas9-mediated knockout and mRNA induction). In addition, in vivo MS models using FOXP3 reporter mice are developed. The VLAIO-inspired collaboration with industry lead our team to multiple research collaborations with Flemish companies using the team’s and Paulien’s expertise in flow cytometry, in vivo MS models (including models new to the team such as the PLP-induced EAE and 2D2 transgenic mice), T cell and Treg biology and in vitro BBB assays. Paulien is leading and managing these projects. The team’s ultimate goal of these unique and innovative collaborations is to bring our research and knowledge towards the clinic.

Gayel Duran: Postdoctoral fellow

Gayel Duran (°1996) is a postdoctoral researcher in the CBN lab. After her bachelor in psychobiology at the University of Amsterdam she proceeded her academic path at Maastricht University. Here she finished the research master Cognitive & Clinical Neuroscience with a specialization in Drug Development and Neurohealth. During her PhD she focussed on the effects of inflammasome activation of T cells after migration over the blood brain barrier. After her successful thesis defense in December 2024 she is now working as a postdoc in the lab of Dr. Bieke Broux. Here she will further unravel the link between brain barriers, inflammasome activation and immune cell migration. Supervised by Dr. Bieke Broux she will analyze human blood and brain samples using flow cytometry and immunohistochemistry. Further she will use a mouse model to investigate contribution to disease pathogenesis.

Lisa Schuetz: PhD candidate

Lisa T Schuetz (°1996) started her joint PhD project at Hasselt University and Maastricht University in 2022. At the end of her Neuroscience master program at Maastricht University she did a 9-month internship in Prof. Michela Matteoli’s lab (Milan) to gain more expertise in neuroimmunology. Supervised by Bieke Broux, Tim Vanmierlo and Kristiaan Wouters, Lisa combines her expertise on immunometabolism and neuroscience to investigate how obesity increases the risk of Alzheimer’s dementia. Therefore, she characterizes T helper cells in human lean and obese adipose tissue and uses a mouse model to understand the contribution of the adipose tissue-brain axis on neurodegeneration.

Sarah Chenine: PhD candidate

Sarah Chenine (°1997) started a joint PhD project at Hasselt University and Maastricht University on November 1^st 2021, funded by ‘Fonds Wetenschappelijk Onderzoek’ (FWO). She did her internship working on epigenetics in oligodendrocytes at Hasselt University and graduated in the research master Cognitive & Clinical Neuroscience with a specialization in Drug Development and Neurohealth, at Maastricht University. Supervised by Profs. Bieke Broux, Tim Vanmierlo and Daniel van den Hove, she now focusses on the epigenetic features of regulatory T cells and their restoring capacity during neurodegeneration.

Janne Verreycken: PhD candidate

Janne Verreycken (°2000) started her PhD in November 2023 funded by the special research fund of Hasselt University. This allowed her to build on the research she conducted during her seven-month internship in the CBN lab, where she focused on the brain barrier-repairing capacity of regulatory T cells in multiple sclerosis. In November 2024, she acquired funding from ‘Fonds Wetenschappelijk Onderzoek’ (FWO) for her PhD project, which explores the pro-inflammatory phenotype switch of regulatory T cells following blood-brain barrier migration.

Daphne Lintsen: PhD candidate

Daphne Lintsen (°1998) started her PhD at Hasselt University in November 2023 on a ‘Fonds Wetenschappelijk Onderzoek’ (FWO) funded project. After her bachelor in biology at Hasselt University, she proceeded her academic path at Radboud University Nijmegen where she obtained her master in medical biology with a specialization in human biology. Under the guidance of prof. dr. Bieke Broux in collaboration with prof. dr. Kristiaan Wouters  and prof. dr. Kenneth Verboven, she focuses on the impact of adipose tissue-derived extracellular vesicles (EVs) on the blood brain barrier (BBB) in the context of obesity. The project involves in-depth characterization of human adipose tissue-derived EVs and a combination of in vitro and in vivo models to study the BBB. Hereto, she aims to understand the adipose tissue-brain axis in the light of BBB disruption.

Xue Zhong: PhD candidate

Xue is a clinician specializing in rheumatology and immunology from China. With her strong clinical foundation, Xue is dedicated to understanding how dietary factors influence neuroimmune interactions and contribute to disease pathology. Currently, Xue is conducting research on the mechanisms through which salt intake affects blood-brain barrier integrity, with implications for neurological and autoimmune diseases.

Brecht Moonen: PhD candidate

Brecht Moonen, born in 2000 and raised in Grote-Brogel, Limburg, Belgium, achieved distinction in obtaining his master's degree in Biomedical Sciences from Hasselt University. Throughout his academic journey, Brecht has demonstrated a keen interest in the intersection of lipid metabolism in immunity and multiple sclerosis, which he passionately pursued from the onset of his master's program. To deepen his understanding, he embarked on a senior internship in Lund, Sweden.

Full publication list: Google Scholar

1 Rapamycin rescues loss of function in blood-brain barrier–interacting Tregs
Baeten, P., Hamad, I., Hoeks, C., Hiltensperger, M., Van Wijmeersch, B., Popescu, V., Aly, L., Somers, V., Korn, T., Kleinewietfeld, M., Hellings, N.*, Broux, B.*
* equally contributing authors
JCI insight 2024 Feb; 9(7) p.e167457.

2 Differential Runx3, Eomes, and T‐bet expression subdivides MS‐associated CD4+ T cells with brain‐homing capacity
Hoeks, C.*, Puijfelik, F. V.*, Koetzier, S. C.*, Rip, J., Corsten, C. E., Wierenga‐Wolf, A. F., Melief, M. J., Stinissen, P., Smolders, J., Hellings, N., Broux, B.*, van Luijn, M. M*
* equally contributing authors
European Journal of Immunology 2024 Feb, 54(2), 2350544.

3 Cerebral microvascular endothelial cell-derived extracellular vesicles regulate blood− brain barrier function
Hosseinkhani, B.*, Duran, G.*, Hoeks, C., Hermans, D., Schepers, M., Baeten, P., Poelmans, J., Coenen, B., Bekar, K., Pintelon, I., Timmermans, J.P., Vanmierlo, T., Michiels, L., Hellings, N., Broux, B.*
* equally contributing authors
Fluids and Barriers of the CNS 2023 Dec, 20(1), 95.

4 Oncostatin M triggers brain inflammation by compromising blood–brain barrier integrity
Hermans, D.*, Houben, E.*, Baeten, P., Slaets, H., Janssens, K., Hoeks, C., Hosseinkhani, B., Duran, G., Bormans, S., Gowing, E. and Hoornaert, C., Beckers, L., Fung, W. K., Schroten, H., Ishikawa, H., Fraussen, J., Thoelen, R., de Vries, H. E., Kooij, G., Zandee, S., Prat. A., Hellings, N.*, Broux, B*.
* equally contributing authors
Acta Neuropathologica 2022 June, 144(2), 259-281.

5 Interleukin-26, preferentially produced by TH17 lymphocytes, regulates CNS barrier function
Broux B.*, Zandee S.*, Gowing E., Charabati M., Lécuyer M.A., Tastet O., Hachehouche L., Bourbonnière L., Ouimet J.P., Lemaitre F., Larouche S., Cayrol R., Bouthillier A., Moumdjian R., Lahav B., Poirier J., Duquette P., Arbour N., Peelen E.*, Prat A.*
* equally contributing authors
Neurology: Neuroimmunology and Neuroinflammation 2020 Aug 11;7(6):e870.