Microglia (brain macrophages) are the primary immune cells of the central nervous system and perform continuous surveillance to maintain brain tissue homeostasis. The microglia respond to neuronal stress and damage. Sustained activation of the microglia results in exaggerated inflammatory activation and subsequent tissue damage, which is observed in neurodegenerative diseases.
Alternatively, inflammation and neuroinflammation can induce a state of suppressed immune activity in the microglia, called endotoxin tolerance. This condition is associated with reduced neuronal support by the microglia and a decreased capacity to respond to inflammatory stimuli. The research is focused on neuron–glia signalling and on the epigenetic regulation of different microglia phenotypes and associated functionalities with an emphasis on brain ageing and neurodegenerative conditions.
The investigators combine cell and organotypical slice cultures, mouse genetics, state-of-the-art cell isolation procedures in combination with genetic and epigenetic tools to delineate the molecular and epigenetic pathways that determine microglia function. Our studies provide a genome-wide insight in the genetic and epigenetic regulation of microglia function in the normal and diseased brain and could lead to the identification of novel therapeutic targets.
Head of the Section Molecular Neurobiology
Professor of Molecular Neuroimmunology
Neuroscience, epigenetics, innate immunity
Jody de Jong Msc.
Tiago Medeiros Furquim Mendonça
Marion Wijering Msc.
All Publications: mepa page
- Wes PD, Holtman IR, Boddeke HWGM, Möller T, Eggen BJ (2016)Next generation transcriptomics and genomics elucidate biological complexity of microglia in health and disease. Glia
- Holtman IR, Noback M, Bijlsma M, Duong KN, van der Geest MA, Ketelaars PT, Vainchtein ID, Eggen BJ*, Boddeke HWGM* (2015) Glia Open Access Database (GOAD): A Comprehensive Gene Expression Encyclopedia of Glia cells in Health and Disease. Glia
- Schaafsma W, Zhang X, van Zomeren KC, Jacobs S, Georgieva PB, Wolf SA, Kettenmann H, Janova H, Saiepour N, Hanisch U-K, Meerlo P, van den Elsen PJ, Brouwer N, Boddeke HWGM, Eggen BJ (2015) Long-lasting pro-inflammatory suppression of microglia by LPS-preconditioning is mediated by RelB-dependent epigenetic silencing. Brain Behavior and Immunity
- Holtman IR, Raj DD, Miller JA, Schaafsma W, Yin Z, Brouwer N, Wes, PD, Möller T, Orre M, Kamphuis W, Hol EM, Boddeke HWGM, Eggen BJ(2015)Induction of a common microglia gene expression signature by aging and neurodegenerative conditions: a co-expression meta-analysis. Acta Neuropath Comm
- Raj D, Jaarsma D, Holtman IR, Olah M, Ferreira FM, Schaafsma W, Brouwer N, Meijer M, de Waard MC, van der Pluijm I, Brandt R, Kreft KL, Laman JD, de Haan G, Biber KP, Hoeijmakers JHJ, Eggen BJ, Boddeke HWGM (2014) Priming of Microglia in a DNA Repair Deficient Model of Accelerated Aging. Neurobiol of Aging
- Vainchtein ID, Vinet J, Brouwer N, Brendecke S, Biagini G, Biber KP, Boddeke HWGM, Eggen BJ (2014) In acute experimental autoimmune encephalomyelitis, infiltrating macrophages are immune activated, whereas microglia remain immune suppressed. Glia
- Kooistra SM, van den Boom V, Thummer RP, Johannes F, Wardenaar R, Tesson BM, Veenhoff LM, Fusetti F, O’Neill LP, Turner BM, de Haan G, Eggen BJ (2010) UTF1 regulates ES cell chromatin organization and gene expression. Stem Cells
- Plaza-Menacho I, van der Sluis T, Hollema H, Gimm O, Buys CH, Magee AI, Isacke CM, Hofstra RM, Eggen BJ (2007) Ras/ERK1/2-mediated STAT3 Ser727 phosphorylation by familial medullary thyroid carcinoma-associated RET mutants induces full activation of STAT3 and is required for c-fos promoter activation, cell mitogenicity, and transformation. J Biol Chem
- van den Boom V, Kooistra SM, Boesjes M, Geverts B, Houtsmuller AB, Monzen K, Komuro I, Essers J, Drenth-Diephuis LJ, Eggen BJ (2007) UTF1 is a chromatin-associated protein involved in ES cell differentiation. J Cell Biol
- Benus GF, Wierenga AT, de Gorter DJ, Schuringa JJ, van Bennekum AM, Drenth-Diephuis LJ, Vellenga E, Eggen BJ (2005)Inhibition of the Transforming Growth Factor β (TGFβ) Pathway by Interleukin-1β Is Mediated through TGFβ-activated Kinase 1 Phosphorylation of SMAD3. Mol Biol Cell
- Drs. W. Schaafsma (2014), Histocell Tissue Engineering, Bilbao, Spain (Project Leader)
- Dr V. Kannan (2014)
- Dr R.P. Thummer (2010), Department of Biosciences and Bioengineering, Indian Institute of Technology, Guwahati, India (Assistant Professor)
- Dr. Duco Schriemer (2016)
- Dr I.R Holtman (2016), Glass Laboratory, School of Medicine, University of California, San Diego
- Dr. I. D. Vainchtein (2016), Molofsky Laboratory, School of Medicine, University of California, San Fransisco
- Dr D.D.A. Raj (2016) Department of Translational Neuroscience, UMC Utrecht