Elga de Vries

Research Line

Neuro-immunology: The neurovascular unit in health and disease

Altered activation of the immune system, neuroinflammation (marked by activated astrocytes and microglia), and dysfunction of the neuro-protective brain barriers are pathological hallmarks of many neurodegenerative disorders, such as multiple sclerosis (MS), various forms of dementia, including Alzheimer’s disease (AD), and stroke. It becomes increasingly clear that chronic neuroinflammation, an altered immune response and neurovascular dysfunction may even be causal for onset and progression of such cognitive disorders, but underlying mechanisms remain unknown. The translational research of the De Vries group is therefore focused on understanding how alterations at the level of the immune system and the brain barriers underlie neuroinflammatory and neurodegenerative conditions. In the current research, we aim to define underlying pathways that initiate neuro-inflammation as potential targets for treatment and identify if such alterations may serve as biomarkers for disease in well-defined patient cohorts. A better understanding of such pathological processes may in future not only lead to new diagnostic tools that reflect ongoing neuro-inflammation and brain barrier dysfunction, but may also lead to potential novel intervention strategies to fight neurogical disorders.

Key publications

van Olst L, Coenen L, Nieuwland JM, Rodriguez-Mogeda C, de Wit NM, Kamermans A, Middeldorp J, de Vries HE. Crossing borders in Alzheimer’s disease: A T cell’s perspective. Adv Drug Deliv Rev. 2022 Sep;188:114398. doi: 10.1016/j.addr.2022.114398. Epub 2022 Jun 30.PMID: 35780907

Rodríguez-Lorenzo S, van Olst L, Rodriguez-Mogeda C, Kamermans A, van der Pol SMA, Rodríguez E, Kooij G, de Vries HE. Single-cell profiling reveals periventricular CD56^brightNK cell accumulation in multiple sclerosis. 2022 May 10;11:e73849. doi: 10.7554/eLife.73849.PMID: 35536009

Wevers NR, Nair AL, Fowke TM, Pontier M, Kasi DG, Spijkers XM, Hallard C, Rabussier G, van Vught R, Vulto P, de Vries HE, Lanz HL. Modeling ischemic stroke in a triculture neurovascular unit on-a-chip. Fluids Barriers CNS. 2021 Dec 14;18(1):59. doi: 10.1186/s12987-021-00294-9.PMID: 34906183

Rodríguez-Lorenzo S, Ferreira Francisco DM, Vos R, van Het Hof B, Rijnsburger M, Schroten H, Ishikawa H, Beaino W, Bruggmann R, Kooij G, de Vries HE. Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis.Acta Neuropathol Commun. 2020 Mar 19;8(1):35. doi: 10.1186/s40478-020-00903-y.PMID: 32192527

Wouters E, de Wit NM, Vanmol J, van der Pol SMA, van Het Hof B, Sommer D, Loix M, Geerts D, Gustafsson JA, Steffensen KR, Vanmierlo T, Bogie JFJ, Hendriks JJA, de Vries HE. Liver X Receptor Alpha Is Important in Maintaining Blood-Brain Barrier Function.Front Immunol. 2019 Jul 31;10:1811. doi: 10.3389/fimmu.2019.01811. eCollection 2019.PMID: 31417573

van Olst L, Coenen L, Nieuwland JM, Rodriguez-Mogeda C, de Wit NM, Kamermans A, Middeldorp J, de Vries HE. Crossing borders in Alzheimer’s disease: A T cell’s perspective. Adv Drug Deliv Rev. 2022 Sep;188:114398. doi: 10.1016/j.addr.2022.114398. Epub 2022 Jun 30.PMID: 35780907

Rodríguez-Lorenzo S, van Olst L, Rodriguez-Mogeda C, Kamermans A, van der Pol SMA, Rodríguez E, Kooij G, de Vries HE. Single-cell profiling reveals periventricular CD56^brightNK cell accumulation in multiple sclerosis. 2022 May 10;11:e73849. doi: 10.7554/eLife.73849.PMID: 35536009

Wevers NR, Nair AL, Fowke TM, Pontier M, Kasi DG, Spijkers XM, Hallard C, Rabussier G, van Vught R, Vulto P, de Vries HE, Lanz HL. Modeling ischemic stroke in a triculture neurovascular unit on-a-chip. Fluids Barriers CNS. 2021 Dec 14;18(1):59. doi: 10.1186/s12987-021-00294-9.PMID: 34906183

Rodríguez-Lorenzo S, Ferreira Francisco DM, Vos R, van Het Hof B, Rijnsburger M, Schroten H, Ishikawa H, Beaino W, Bruggmann R, Kooij G, de Vries HE. Altered secretory and neuroprotective function of the choroid plexus in progressive multiple sclerosis.Acta Neuropathol Commun. 2020 Mar 19;8(1):35. doi: 10.1186/s40478-020-00903-y.PMID: 32192527

Wouters E, de Wit NM, Vanmol J, van der Pol SMA, van Het Hof B, Sommer D, Loix M, Geerts D, Gustafsson JA, Steffensen KR, Vanmierlo T, Bogie JFJ, Hendriks JJA, de Vries HE. Liver X Receptor Alpha Is Important in Maintaining Blood-Brain Barrier Function.Front Immunol. 2019 Jul 31;10:1811. doi: 10.3389/fimmu.2019.01811. eCollection 2019.PMID: 31417573

Group members

Carla Rodriguez Mogeda, PhD

PhD student
Postdoctoral researcher My research focuses on understanding brain barriers immunity in neurodegeneration, with a special focus on meningeal inflammation in progressive multiple sclerosis. I am specifically interested in the communication between innate and adaptive immune cells within these brain barriers and their relation to brain pathology. To do this, I use different single-cell techniques for proteomics and transcriptomics, combined with confocal and multispectral microscopy.

Chaja van Ansenwoude, MSc

PhD student
My research is focused on the role of NK cells in MS pathogenesis, specifically CD56bright NK cells. This cell population appears to accumulate in the brain of MS patients and exhibits an immunomodulatory and migratory phenotype, suggesting a protective role for these cells in MS. We aim to further unravel the mechanisms underlying CD56bright NK cell effector function by studying cellular interactions, immunoregulatory and neuroprotective capacities, mechanisms of migration, and correlations with clinical markers. For this, I will make use of multispectral microscopy, single cell mass cytometry, in vitro BBB and BCSFB models, and co-culture experiments.

Henrique Nogueira Pinto

Postdoctoral researcher
My research focuses on how cellular crosstalk within the neurovascular unit instructs and maintains blood–brain barrier function, and how disruption of this crosstalk contributes to neurological disease. Using human iPSC-derived models and advanced organ-on-chip platforms, I model neurovascular signaling in order to investigate drug delivery strategies and disease-associated BBB dysfunction in conditions such as Alzheimer’s disease and ischemic stroke

Inge Mulder

Guest assistant professor
Guest Assistant professor I am a translational neuroscientist and works as Assistant Professor both at the MCBI as well as the Biomedical Engineering & Physics department at Amsterdam UMC. My group focusses on the cerebral microcirculation and the neurovascular changes that accompany stroke. Our multidisciplinary team combines pre-clinical in vivo imaging (2-photon microscopy, MRI) with in vitro blood-brain barrier models and patient data & material. This combination forms a robust and highly interconnected stroke and neurovascular research platform. My work aims to understand microvascular dysfunction during occlusion of small and large vessels and after reperfusion. In my work I explore how microvascular dynamics and interventions influence stroke recovery and brain function. Recently, our team also entered the world of microplastics, where I use my neurovascular expertise to unravel how microplastics behave when entering the vasculature, how they can cross the BBB, and the acute and chronic damage these particles can cause.

Lena Nieswandt, PhD

Targeting the ChP-CSF axis to combat progression in multiple sclerosis Multiple sclerosis (MS) affects millions worldwide, with a notably high prevalence in the Netherlands – particularly among women. While disease-modifying therapies (DMTs) have seen high success rates in treating relapsing-remitting MS, progressive patients are still waiting for a clinical breakthrough. My research focuses on progression independent of relapse activity (PIRA), the decline that occurs even in the absence of active relapses. I investigate the role of the choroid plexus (ChP)-cerebrospinal fluid (CSF) axis as potential key driver of this progression. My work explores how altered CSF, produced by the MS ChP, compromises the ependymal lining within the periventricular environment. We hypothesize that this weakened barrier allows cytotoxic factors and immune cells to infiltrate the brain parenchyma and drive neurodegenerative damage. To bridge the gap between bench and bedside, we utilize. - Mechanistic insight by combining findings from post-mortem tissue and in vivo CSF analyses with in vitro modeling of the brain-CSF barrier, and - Clinical context through close collaboration with Clinical Neuroscience (ANW) (and integration with novel imaging biomarkers. Ultimately, our goal is to uncover new ways to predict and treat PIRA, moving discoveries from the lab bench to the clinic to improve the lives of those with progressive MS.

Matthew Mason

Postdoctora; Student
Matthew Mason Postdoctoral researcher My research is focused on multiple sclerosis (MS), in particular on endogenous type I interferon production in and around MS lesions. I look at its relationship to lesion formation, immune cell infiltration and activation, immunoglobulin production and interferon response gene expression. To do this I use immunohistochemistry, advanced image analysis techniques, bioinformatics, and in vivo and in vitro models.

Merel Rijnsburger

Guest assistant professot
I am a translational neuroscientist and works as Assistant Professor both at the MCBI as well as the Biomedical Engineering & Physics department at Amsterdam UMC. My group focusses on the cerebral microcirculation and the neurovascular changes that accompany stroke. Our multidisciplinary team combines pre-clinical in vivo imaging (2-photon microscopy, MRI) with in vitro blood-brain barrier models and patient data & material. This combination forms a robust and highly interconnected stroke and neurovascular research platform. My work aims to understand microvascular dysfunction during occlusion of small and large vessels and after reperfusion. In my work I explore how microvascular dynamics and interventions influence stroke recovery and brain function. Recently, our team also entered the world of microplastics, where I use my neurovascular expertise to unravel how microplastics behave when entering the vasculature, how they can cross the BBB, and the acute and chronic damage these particles can cause.

Lena Nieswandt, PhD

Targeting the ChP-CSF axis to combat progression in multiple sclerosis Multiple sclerosis (MS) affects millions worldwide, with a notably high prevalence in the Netherlands – particularly among women. While disease-modifying therapies (DMTs) have seen high success rates in treating relapsing-remitting MS, progressive patients are still waiting for a clinical breakthrough. My research focuses on progression independent of relapse activity (PIRA), the decline that occurs even in the absence of active relapses. I investigate the role of the choroid plexus (ChP)-cerebrospinal fluid (CSF) axis as potential key driver of this progression. My work explores how altered CSF, produced by the MS ChP, compromises the ependymal lining within the periventricular environment. We hypothesize that this weakened barrier allows cytotoxic factors and immune cells to infiltrate the brain parenchyma and drive neurodegenerative damage. To bridge the gap between bench and bedside, we utilize - Mechanistic insight by combining findings from post-mortem tissue and in vivo CSF analyses with in vitro modeling of the brain-CSF barrier, and - Clinical context through close collaboration with Clinical Neuroscience (ANW) and integration with novel imaging biomarkers. Ultimately, our goal is to uncover new ways to predict and treat PIRA, moving discoveries from the lab bench to the clinic to improve the lives of those with progressive MS.

Angelica Sabogal Guaqueta

Postdoctoral researcher
My research focuses on understanding brain diseases through human-relevant models, specifically centering on microglia—the brain’s resident immune cells—and their role in neurodegenerative disorders. By combining induced pluripotent stem cells (iPSCs) with 3D brain organoid technologies, I aim to recreate complex in vitro environments to study cellular interactions and disease mechanisms. I am particularly interested in how metabolic and inflammatory changes in microglia drive disease progression. Currently, I am developing an organ-on-a-chip platform to investigate whether metal leachables from dental materials can trigger neurodegenerative and neuroinflammatory processes in the brain.

Tom Halperin

Guest PhD student
My research focuses on B-cell biology in multiple sclerosis and related neurodegenerative diseases, combining neuroimmunology and neuropathology approaches. I study immune processes at central nervous system borders, particularly in the dura mater and leptomeninges, using human postmortem tissue and spatial analysis methods. My work investigates how immune cell populations, including innate-like B cells, relate to brain inflammation and pathological changes in multiple sclerosis and aging. In parallel, I characterize human B1-like cells in peripheral blood and postmortem brain tissue using single-cell phenotyping approaches, with the aim of understanding non-conventional, innate-like B-cell functions. Orcid ID: orcid.org/0000-0002-7994-0905. "