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Stadhouders, Ralph

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Stadhouders, Ralph

Ralph Stadhouders obtained his MSc and PhD degrees (both cum laude) at the Erasmus University and Erasmus MC in Rotterdam (the Netherlands). During this period, he studied gene regulatory mechanisms in developing blood cells at the Department of Cell Biology of the Erasmus MC under the guidance of Dr. Eric Soler and Prof. Frank Grosveld, for which he was awarded the 2017 Steven Hoogendijk Award from the Batavian Society for Experimental Philosophy. He then obtained several postdoctoral fellowships (NWO Rubicon, EMBO LTF and Marie Curie IF) to relocate to Barcelona (Spain) and join the laboratory of Dr. Thomas Graf at the Centre for Genomic Regulation (CRG). There he studied how transcription factors rewire the transcriptome and epigenome during the reprogramming of lymphocytes into pluripotent stem cells. In 2017 he received an NWO Veni fellowship, which he used to return to the Erasmus MC and initiate his own line of research through a collaboration between the Departments of Pulmonary Medicine (Prof. Rudi Hendriks & Prof. Joachim Aerts) and Cell Biology (Prof. Danny Huylebroeck & Prof. Frank Grosveld). Operating at the interface between fundamental and translational science, his current research focuses on understanding the molecular switches that cause lymphocyte dysfunction in immunological diseases and cancer.           

- Research interests

The overarching goal of the Stadhouders laboratory is to decipher the molecular mechanisms that control immune cell phenotypes in both homeostasis and disease to identify targets for therapeutic intervention. We work towards this goal by employing state-of-the-art genomics technology to study gene regulatory mechanisms in mouse and human immune cells. Special emphasis is placed on the identification and characterization of gene regulatory elements and transcription factors critical for lymphocyte dysfunction in asthma, autoimmunity and cancer. Disease-relevant cell populations are obtained from mouse models that mimic human immune disorders and patient material from the clinic or collaborations with nearby hospitals. Our recent efforts have led to the generation of high-resolution genome-wide maps of nuclear architecture, chromatin structure and gene expression during the reprogramming of lymphocytes into pluripotent stem cells. Computational integration of these datasets showed that modifications of 3D chromosomal organization often precede transcriptional changes at key loci, pointing towards a general instructive role for 3D chromatin structure in regulating transcription and cell fate (Stadhouders et al. 2018). In addition, we generated the first epigenome maps of circulating human innate lymphoid cell (ILC) precursors and group 2 ILCs (Lim et al. 2017, Stadhouders et al. 2018). These experiments revealed novel putative regulators of human ILC biology and support a pathogenic role for group 2 ILCs in allergic asthma.

- Selected recent publications

*Shared first authorship
#Corresponding authorship

Stadhouders R#, Vidal E, Serra F, Di Stefano B, Le Dily F, Quilez J, Gomez A, Collombet S, Berenguer C, Cuartero Y, Hecht J, Filion G, Beato M, Marti-Renom MA#, Graf T#. Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming. Nature Genetics50, 238-249 (2018)

Stadhouders R#. Expanding the toolbox for 3D genomics. Nature Genetics doi: 10.1038/s41588-018-0112-1 (2018)

Stadhouders R#, Li BWS, de Bruijn MJW, Gomez A, Rao TN, Fehling HJ, van IJcken WFJ, Lim AI, Di Santo JP, Graf T, Hendriks RW#. Epigenome analysis links gene regulatory elements in group 2 innate lymphocytes to asthma susceptibility. Journal of Allergy and Clinical Immunology doi: 10.1016/j.jaci.2017.12.1006 (2018)

Stadhouders R, Lubberts E, Hendriks RW. A cellular and molecular view of T helper 17 cell plasticity in autoimmunity. Journal of Autoimmunity Dec 21. doi:10.1016/j.jaut.2017.12.007 (2017)

Li BWS, Stadhouders R, de Bruijn MJW, Lukkes M, Beerens DMJM, Brem MD, KleinJan A, Bergen I, Vroman H, Kool M, van IJcken WFJ, Rao TN, Fehling HJ, Hendriks RW. Group 2 Innate Lymphoid Cells Exhibit a Dynamic Phenotype in Allergic Airway Inflammation. Frontiers in Immunology doi: 10.3389/fimmu.2017.01684 (2017)

Lim AI, Li Y, Lopez-Lastra S, Stadhouders R, Paul F, Casrouge A, Serafini N, Puel A, Bustamante J, Surace L, Masse-Ranson G, David E, Strick-Marchand H, Le Bourhis L, Cocchi R, Topazio D, Graziano P, Muscarella LA, Rogge L, Norel X, Sallenave JM, Allez M, Graf T, Hendriks RW, Casanova JL, Amit I, Yssel H, Di Santo JP. Systemic Human ILC Precursors Provide a Substrate for Tissue ILC Differentiation. Cell 6:1086-1100 (2017)

Brouwer RW, van den Hout MC, van IJcken WF, Soler E#, Stadhouders R#. Unbiased Interrogation of 3D Genome Topology Using Chromosome Conformation Capture Coupled to High-Throughput Sequencing (4C-Seq). Methods in Molecular Biology 1507:199-220 (2017)

Stadhouders R*#, Cico A*, Stephen T, Thongjuea S, Kolovos P, Baymaz HI, Yu X, Demmers J, Bezstarosti K, Maas A, Barroca V, Kockx C, Ozgur Z, van Ijcken W, Arcangeli ML, Andrieu-Soler C, Lenhard B, Grosveld F, Soler E#. Control of developmentally primed erythroid genes by combinatorial co-repressor actions. Nature Communications 23;6:8893 (2015)

Ribeiro de Almeida C, Hendriks RW#, Stadhouders R#. Dynamic Control of Long-Range Genomic Interactions at the Immunoglobulin κ Light-Chain Locus. Advances in Immunology 128:183-271 (2015)