Feb 1, 2021
A key regulator for humoral immunity and B lymphoma
Oct 11, 2019
ERC Synergy Grant for viral infection and cellular regulation research
Dec 17, 2018
How liquid droplets grow in cells
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Transcriptional and epigenetic networks and function of HDACs in mammals
Molecular mechanism underlying plasticity
Stem cells give rise to differentiated cells through gradual establishment of lineage-specific gene expression programs. These result from a complex interplay of signal transduction cascades, genetic hierarchies of transcription factors and epigenetic chromatin modifiers. This creates a molecular code unique to each cell type that defines its properties and fate.
We are interested in the molecular mechanisms underlying cellular plasticity and cell-specific gene expression in a genetically tractable system and concentrate on the transcriptional and epigenetic control of lymphoid (B) cell development. For this, we study several transcription factors and epigenetic regulators that may be relevant for B cell development.
Focus on HDACs
In addition, we have a central focus on histone deacetylases (HDACs). Acetylation of histones represents a crucial epigenetic annotation of chromatin, which participates significantly in the regulation of gene expression. In addition, non-histone protein acetylation is involved in an expanding range of cellular processes. HDACs remove acetyl groups from histone N-terminal tails and thereby contribute to chromatin condensation and to the modulation of gene expression. Although the biological role of HDACs in mammals is still poorly understood, it is clear that these proteins are important in cancer as well as in various other diseases such as autoimmunity or neurodegeneration. HDACs therefore are valuable potential therapeutic targets in a number of pathological settings.
We use a broad range of methods, including the generation and analysis of transgenic or conditionally targeted mice as well as functional genomics and proteomics.
This is a list of selected publications from this group. For a full list of publications, please visit our Publications page and search by group name.
Choukrallah MA, Matthias P (2014) The interplay between chromatin and transcription facto networks during B cell development: who pulls the trigger first?Front Immunol 5:15
Du Roure C, Versavel A, Doll T, Cao C, Pillonel V, Matthias G, Kaller M, Spetz JF, Kopp P, Kohler H, Müller M, Matthias P (2014) Hematopoietic overexpression of FOG1 does not affect B-cells but reduces the number of circulating eosinophilsPLOS One 9:e92836
Brunmeir R, Lagger S, Simboeck E, Sawicka A, Egger G, Hagelkruys A, Zhang Y, Matthias P, Miller WJ, Seiser C (2010) Epigenetic regulation of a murine retrotransposon by a dual histone modification markPLoS Genet 6:e1000927
Yamaguchi T, Cubizolles F, Zhang Y, Reichert N, Kohler H, Seiser C, Matthias P (2010) Histone deacetylases 1 and 2 act in concert to promote the G1-to-S progressionGenes Dev 24:455-69
Bordon A, Bosco N, Du Roure C, Bartholdy B, Matthias G, Rolink AG, Matthias P (2008) Enforced expression of the transcriptional coactivator OBF1 impairs B cell differentiation at the earliest stage of developmentPloS ONE. 3:e4007. Epub 2008 Dec 23
Karnowski A, Cao C, Matthias G, Carotta S, Corcoran LM, Martensson IL, Skok JA, Matthias P (2008) Silencing and nuclear repositioning of the l5 gene locus at the pre-B cell stage require Aiolos and OBF-1PLoS ONE. 3:e3568. Epub 2008 Oct 30
Matthias P, Yoshida M, Khochbin S (2008) HDAC6 a new cellular stress surveillance factorCell Cycle 7:7-10
Zhang Y, Kwon S, Yamaguchi T, Cubizolles F, Rousseaux S, Kneissel M, Cao C, Li N, Cheng HL, Chua K, Lombard D, Mizeracki A, Matthias G, Alt FW, Khochbin S, Matthias P (2008) Mice lacking histone deacetylase 6 have hyperacetylated tubulin but are viable and develop normallyMol Cell Biol 28:1688-1701
Boyault C, Zhang Y, Fritah S, Caron C, Gilquin B, Kwon SH, Garrido C, Yao TP, Vourc'h C, Matthias P, Khochbin S (2007) HDAC6 controls major cell response pathways to cytotoxic accumulation of protein aggregatesGenes Dev 21:2172-2181
Kwon S, Zhang Y, Matthias P (2007) The deacetylase HDAC6 is a novel critical component of stress granules involved in the stress responseGenes Dev 21:3381-3394
Bartholdy B, Du Roure C, Bordon A, Emslie D, Corcoran LM, Matthias P (2006) The Ets factor Spi-B is a direct critical target of the coactivator OBF-1Proc Natl Acad Sci USA 103:11665-11670
Boyault C, Gilquin B, Zhang Y, Rybin V, Garman E, Meyer-Klaucke W, Matthias P, Müller CW, Khochbin S (2006) HDAC6-p97/VCP controlled polyubiquitin chain turnoverEMBO J 25:3357-3366
Matthias P, Rolink AG (2005) Transcriptional networks in developing and mature B cellsNature Rev Immunol 5:497-508
Bartholdy B, Matthias P (2004) Transcriptional control of B cell development and functionGene 327:1-23
Lins K, Remenyi A, Tomilin A, Massa S, Wilmanns M, Matthias P, Scholer HR (2003) OBF1 enhances transcriptional potential of Oct1EMBO J 22:2188-2198
Sun J, Matthias G, Mihatsch MJ, Georgopoulos K, Matthias P (2003) Lack of the transcrip- tional coactivator OBF-1 prevents the devel- opment of systemic lupus erythematosus- like phenotypes in Aiolos mutant miceJ Immunol 170:1699-1706
Zhang Y, Li N, Caron C, Matthias G, Hess D, Khochbin S, Matthias P (2003) HDAC-6 interacts with and deacetylates tubulin and microtubules in vivoEMBO J 22:1168-1179
Schubart K, Massa S, Schubart D, Corcoran LM, Rolink AG, Matthias P (2001) B cell development and immunoglobulin gene transcription in the absence of Oct-2 and OBF-1Nature Immunol 2:69-74
Tiedt R, Bartholdy BA, Matthias G, Newell JW, Matthias P (2001) The RING finger protein Siah-1 regulates the level of the transcrip- tional coactivator OBF-1EMBO J 20:4143-4152
Full list of publications
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Ronan’s research focuses on host-pathogen interactions and how our immune system recognises and eliminates microbes. He completed his PhD in Immunology at the Pasteur Institute (France), with Prof J.M. Cavaillon and Dr M. Adib-Conquy, before moving to Scotland and to Australia, working with Prof David Hume and Prof Matt Sweet. Ronan is now a Marie-Curie Action Fellow and has joined the group of Prof P. Matthias, where he investigates the role of histone deacetylases as regulator of the inflammatory and antimicrobial response. Ultimately, his research goal is to discover new mechanisms that can be modulated to enhance our own immune system, rather than targeting directly the microbes.Current reseach
Using a combination of molecular biology, proteomics and microscopy, Ronan characterises new antimicrobial and inflammatory pathways in macrophages, examining in particular the role of histone deacetylases (HDACs). This project could lead to new anti-inflammatory treatments as well as antimicrobial treatments, which are of paramount importance in the context of multi-drug resistant bacteria.Education
• PhD in Immunology, Université Paris Descartes (Paris V), Paris
• Master's degree in Immunology, Université Pierre et Marie Curie (Paris VI), Paris