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.
- 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;10:1811
- Derada Troletti C, Fontijn RD, Gowing E, Charabati M, van Het Hof B, Didouh I, van der Pol SMA, Geerts D, Prat A, van Horssen J, Kooij G, de Vries HE. Inflammation-induced endothelial to mesenchymal transition promotes brain endothelial cell dysfunction and occurs during multiple sclerosis pathophysiology. Cell Death Dis. 2019 18;10(2):45
- Chakraborty A, Kamermans A, van Het Hof B, Castricum K, Aanhane E, van Horssen J, Thijssen VL, Scheltens P, Teunissen CE, Fontijn RD, van der Flier WM, de Vries HE. Angiopoietin like-4 as a novel vascular mediator in capillary cerebral amyloid angiopathy. 2018 1;141(12):3377-3388.
- Kamermans A, Planting KE, Jalink K, van Horssen J, de Vries HE. Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7-mediated chondroitin sulfate proteoglycan production. Glia. 2019;67(1):68-77.
- Beaino W, Janssen B, Kooij G, van der Pol SMA, van Het Hof B, van Horssen J, Windhorst AD, de Vries HE. Purinergic receptors P2Y12R and P2X7R: potential targets for PET imaging of microglia phenotypes in multiple sclerosis. J Neuroinflammation. 2017 22;14(1):259
My research focuses on understanding meningeal inflammation in progressive multiple sclerosis. I am specifically interested in the role of B cells, in how they get to the meninges and how they might interact, directly or indirectly, with other immune cells such as microglia. To do this, I use different single-cell techniques for proteomics and transcriptomics, and confocal and multispectral microscopy..
Hannah van der Stok, MSc
My work focuses on blood brain barrier functioning. I am specifically interested in a protein named FHL2, which potentially plays a role in blood brain barrier dysfunction. Intracellular mechanisms involved in this process are investigated using in vitro models with lentiviral modifications and various molecular assays.
My research is centered on the development of a brain-on-a-chip, combining iPSC-derived cerebral organoids and a bioengineered blood-brain barrier (BBB). This platform will be used to assess the capability of certain compounds to cross the BBB and their neurobiological effects, either in a healthy or disease-specific context.
Inge Mulder, PhD
Senior postdoctoral researcher
My research is focused on the inaccurate reperfusion of the microvasculature of the brain, after recanalization therapy (thrombolysis or thrombectomy) in acute ischemic stroke. I aim to unravel underlying pathophysiological mechanisms of this phenomenon in order to find new therapeutic strategies to improve treatment efficacy. To do this, I use a translational approach including pre-clinical in-vivo 2-photon microscopy, MRI and Mass spectrometry as well as clinical data.
My research focusses on the (neuro)immunological processes that underlie Alzheimer's disease, MS and aging. For this purpose I utilize single-cell mass cytometry (CyTOF) and confocal imaging. Microglia and T cells are my favorite cells.
I focus mainly on lipid mediators in stroke and subarachnoid hemorrhage. In doing so I hope to explore how these lipid mediators modulate these pathologies. Specifically, the immunological response and that of the cells that make up the NVU is of great interest to me. For that purpose I am currently using LC-MS/MS, as well as trying to set a up a in vitro stroke model and hope to make use of 2-photon microscopy in the future.
My research focuses on the blood-brain barrier in health and disease on a molecular level. Using in vitro cell systems and post-mortem human brain tissue I try to understand specific pathways that are necessary for maintaining proper barrier function.
My research focuses on leukodystrophies, which are genetic disorders that primarily affect the brain white matter. More specifically, I study how the neurovascular unit is involved in these diseases. In the past years, the neurovascular unit has been overlooked in leukodystrophies, while it can have significant implications in the disease progression and in treatments. Using a multidisciplinary approach, I collaborate with pathologists, clinicians and biologists in order to unravel the underlying mechanisms in these diseases. For these studies, I use human post-mortem tissue, in vivo and in vitro approaches.
My work focuses on the blood-brain barrier, in particular on the endothelial component thereof. Mechanisms of blood-brain barrier failure in neurodegenerative diseases are assessed using in vitro models, impedance measurements, lentiviral genetic modification and various biochemical and molecular biological techniques.
Susanne van der Pol, Ing
Expertise in cell isolations, iPSC, cell-based assays, immunostainings (IHC, ICC, IF), CyTOF, FACS.
My research interests center around the neurovascular crosstalk in health and disease, especially in Multiple Sclerosis. In addition, my research focuses on immunomodulatory lipids to promote neurovascular health. High-throughput analysis is used to identify biomarkers for prediction of disease state, disease progression and therapeutic response in Multiple Sclerosis.