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. The role of adaptive-to-innate phenotype switch in T helper cells in neurodegeneration
   Studying atypical characteristics of T helper cells in MS, including inflammasome activation and acquired cytotoxicity, and how this contributes to disease progression.
3. Adipose tissue-brain axis as environmental trigger of neuroinflammation
   Examining the role of adipose tissue-derived T helper cells in triggering neuroinflammation and identifying other dietary influences on BBB permeability in this context.

• (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 a junior group leader and head of the research line on the blood brain barrier in the NIC&R lab of Prof. Dr. Niels Hellings 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), who is an expert in the field of blood brain barrier biology and disruption in multiple sclerosis. For her return to the lab of Prof. Dr. Hellings, 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.

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 is experienced in in vitro BBB modelling and human Treg assays (FACS, extended 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.

Doryssa Hermans: PhD defended!

Doryssa Hermans (°1996) started her PhD on October 1st 2019 as part of the NIC&R lab, funded by the special research fund of Hasselt University. After a 3 month research stay in the lab of Prof. Dr. Elga de Vries (Amsterdam) during her master’s thesis, she decided to start a PhD on the topic of immune cell migration in multiple sclerosis. Supervised by Dr. Bieke Broux and Prof. Dr. Niels Hellings, she focusses on the specific targeting of pathogenic T lymphocyte migration across the blood-brain barrier in MS, which is the future therapeutic outlook. For her research, she specializes in mouse and human BBB-endothelial cell culture, in vitro leukocyte adhesion and migration assays, flow cytometry and cell sorting of mouse and human lymphocytes, and different in vivo mouse models for MS.

Gayel Duran: PhD student

Gayel Duran (1996) started as a PhD student in the team of Bieke Broux on November 1 st 2020 funded by the special research fund of Hasselt University. After her bachelor in psychobiology at the University of Amsterdam she proceeded her academic path at Maastricht University. Here she graduated the research master Cognitive & Clinical Neuroscience with a specialization in Drug Development and Neurohealth. During her masters she did a nine-month internship in the USA at Thomas Jefferson University investigating the effects of IL-11 on MS disease pathology. In her PhD she will focus on the effects of inflammasome activation induced by mitochondrial impairment on the local tissue damage in the brains of MS patients. 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 student

Lisa T Schuetz (°1996) started her joint PhD project at Hasselt University and Maastricht University at the beginning of 2022, funded by the special research fund of Hasselt. After her bachelor in Molecular Medicine at the University of Innsbruck, she followed her research interests and started the research master ‘Cognitive & Clinical Neuroscience’ with a specialization in ‘Fundamental Neuroscience’ at Maastricht University. At the end of her master program she did a 9-month internship in Prof. Michela Matteoli’s lab (Milan) to gain more expertise in neuroimmunology. Supervised by Profs. Bieke Broux and Kristiaan Wouters, Lisa will combine her expertise on immunometabolism and pro-inflammatory T helper (Th) cells to investigate how obesity increases the risk of neurodegenerative diseases. Therefore, she will further characterize Th cells in human lean and obese adipose tissue and blood samples and use a mouse model to understand the contribution of the adipose tissue-brain axis on neurodegeneration.

Sarah Chenine: PhD student

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 student

Janne Verreycken (°2000) started her PhD in November 2023 funded by the special research fund of Hasselt University. During her master’s studies, she performed a seven-month internship in the CBN lab, where she focused on the brain barrier-repairing capacity of regulatory T cells in multiple
sclerosis. In this context, she visited the lab of Prof. Roosmarijn Vandenbroucke in Gent, who is an
important collaborator in this project. Under the guidance of Prof. Bieke Broux, she will continue this research during her PhD. Her project involves the use of in vitro and in vivo models to study brain barrier disruption. Furthermore, she will employ flow cytometry to analyze human blood samples.

Daphne Lintsen: PhD student

Daphne Lintsen (1998) started her PhD at Hasselt University in November 2023, in the context of a ‘Fonds Wetenschappelijk Onderzoek’ (FWO) project. After her bachelor in biology at Hasselt University, she proceeded her academic path at Radboud University Nijmegen where she obtained her master Medical Biology with a specialization in Human Biology. During her final 6-month internship, she investigated the angiogenic and immunomodulatory
effect of nanovesicles in ischemic stroke in the research group of prof. dr. Annelies Bronckaers (UHasselt). In her PhD, she will proceed her career working on (nano) vesicles, investigating whether extracellular vesicles (EVs) released by inflamed adipose tissue trigger blood brain barrier disruption. Under the supervision of prof. dr. Bieke Broux and prof. dr.Kenneth Verboven she will perform an in-depth characterization of human-derived adipose tissue released EVs and analyze EV-mediated blood brain barrier impairment in vitro. The
mechanistic link between human-derived adipose tissue released EVs and
neuroinflammation will be investigated in vivo using mouse models.

Master students

Joke Aerts

Full publication list: Google Scholar

1. “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., Hoornaert C., Beckers L., Fung WK., Schroten H., Ishikawa H., Fraussen J., Thoelen R., de Vries HE., Kooij G., Zandee S., Prat A., Hellings N.*, Broux B.*
   * equally contributing authors Acta Neuropathol. 2022 Aug;144(2):259-281.
   
   
2. "Improving the efficacy of regulatory T cell therapy"
   Baeten P., Van Zeebroeck L., Kleinewietfeld.., Hellings n., Broux B.
   Clin Rev Allergy Immunol 2021 Jul 5;1-19.
   
   
   
3. “Oncostatin M-induced astrocytic tissue inhibitor of metalloproteinase-1 drives remyelination”
   Houben E.*, Janssens K.*, Hermans D., Van den Haute C., Schepers M., Vanmierlo T., Vandooren J., Lambrichts I., Baekelandt V., Opdenakker G., Baron W., Broux B.*, Slaets H.*, Hellings N.*
   * equally contributing authors
   Proc Natl Acad Sci U S A. 2020 Mar 3;117(9):5028-5038.
   
   
   
4. “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.
   
   
   
5. “EGFL7 reduces CNS inflammation in mouse”
   Larochelle C.*, Uphaus T.*, Broux B., Gowing E., Paterka M., Michel L., Dudvarski Stankovic N., Bicker F., Lemaître F., Prat A., Schmidt M.H.H.*, Zipp F.*
   * equally contributing authors
   Nature Communications 2018 Feb 26;9(1):819.