M.P. (Menno) Creyghton, PhD

Deciphering how cells can exist in the diverse cellular states that make up a functional organism while carrying the same genomic information is a major challenge in biology. Transcription factors are responsible for the deposition of epigenomic modifications upon the genome that serve as instructions as to how the genome is being read in each different cell type, thus allowing the cell to adopt a specialized state. Furthermore, these instructions are highly dynamic during development and can change under the influence of extracellular cues presenting the cells with the ability to respond to changes in their environment.

The Creyghton group uses comparative epigenomics and single cell analyses to understand these gene regulatory processes in early embryonic development focusing on promoters and enhancers as the functional unit of transcription. These experiments are combined with functional assays using CRISPR-Cas9 in stem cell-based culture systems and model organisms so as to discover relevant regulatory changes that lead to a variety of disorders including neuropsychiatric and neurodegenerative diseases as well as cancer.

Contact information:
m.creyghton@erasmusmc.nl

Erasmus MC
Dr Molewaterplein 40
3015 GD  Rotterdam

Dept. of Developmental Biology
Room Ee-900
Tel: +31 10 7043966

Menno Creyghton received his MSc in genetics from the Free University in Amsterdam, in 1999. He did his graduate research at The Netherlands Cancer Institute in the group of René Bernards and received his PhD from Utrecht University in 2006 for his work on genetic screens and phosphatases in cancer. After his graduate research he was awarded a KWF fellowship to do postdoctoral research in the Laboratory of Rudolf Jaenisch at the Whitehead Institute for Biomedical Research in Cambridge, USA where he worked on gene regulation and cell state changes in induced pluripotent stem cells. In 2011 he started an independent research group at the Hubrecht Institute for developmental biology and stem cell research focusing on gene regulation in brain development, evolution and disease. In 2019 his laboratory moved to the department of developmental biology at the Erasmus university medical center where he was appointed Associate Professor.

Castelijns B, Mirna L. Baak ML, Timpanaro IS, Wiggers CRM, Vermunt MW, Shang P, Kondova I, Geeven G, Bianchi V, de Laat W, Geijsen N, Creyghton MP., Hominin-specific regulatory elements selectively emerged in oligodendrocytes and are disrupted in autism patients Nat Commun. 2020 Jan 16, 10.1038/s41467-019-14269-w

Wiggers CRM, Baak ML, Sonneveld E, Nieuwenhuis EES, Bartels M, Creyghton MP. AML Subtype Is a Major Determinant of the Association between Prognostic Gene Expression Signatures and Their Clinical Significance. Cell Rep. 2019 Sep 10;28(11):2866-2877.e5.

Bertolini JA, Favaro R, Zhu Y, Pagin M, Ngan CY, Wong CH, Tjong H, Vermunt MW, Martynoga B, Barone C, Mariani J, Cardozo MJ, Tabanera N, Zambelli F, Mercurio S, Ottolenghi S, Robson P, Creyghton MP, Bovolenta P, Pavesi G, Guillemot F, Nicolis SK, Wei CL. Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance. Cell Stem Cell. 2019 Mar 7;24(3):462-476.e6

Lacraz GPA, Junker JP, Gladka MM, Molenaar B, Scholman KT, Vigil-Garcia M, Versteeg D, de Ruiter H, Vermunt MW, Creyghton MP, Huibers MMH, de Jonge N, van Oudenaarden A, van Rooij E. Tomo-Seq Identifies SOX9 as a Key Regulator of Cardiac Fibrosis During Ischemic Injury. Circulation. 2017 Oct 10;136(15):1396-1409.

Vermunt, M.W., Tan S.C., Castelijns B., Geeven, G., Reinink, P., de Bruijn, E., Kondova I., Persengiev S., Netherlands Brain Bank; Bontrop R., Cuppen, E., de Laat, W. and Creyghton M.P. Epigenomic annotation of gene regulatory alterations during evolution of the primate brain. Nature Neurosci. 2016 Jan 26;

Amin S, Neijts R, Simmini S, van Rooijen C, Tan SC, Kester L, van Oudenaarden A, Creyghton MP, Deschamps J. Cdx and T Brachyury Co-activate Growth Signaling in the Embryonic Axial Progenitor Niche. Cell Rep. 2016 Dec 20;17(12):3165-3177

Neijts R, Amin S, van Rooijen C, Tan S, Creyghton MP, de Laat W, Deschamps J. Polarized regulatory landscape and Wnt responsiveness underlie Hox activation in embryos. Genes Dev. 2016 Sep 1;30(17):1937-42. Impact facor: 12.6

Houtepen LC, Vinkers CH, Carrillo-Roa T, Hiemstra M, van Lier PA, Meeus W, Branje S, Heim CM, Nemeroff CB, Mill J, Schalkwyk LC, Creyghton MP, Kahn RS, Joëls M, Binder EB, Boks MP. Genome-wide DNA methylation levels and altered cortisol stress reactivity following childhood trauma in humans. Nat Commun. 2016 Mar 21;7:

 Geeven G., Zhu Y., Kim B.J., Bartholdy B.A., Yang S.M., Macfarlan T.S., Gifford W.D., Pfaff S.L., Verstegen M.J., Pinto H., Vermunt M.W., Creyghton M.P., Wijchers P.J., Stamatoyannopoulos J.A., Skoultchi A.I., de Laat W. Local compartment changes and regulatory landscape alterations in histone H1-depleted cells. Genome Biol. 2015 Dec 23;16(1):289.

Peeters J.G., Vervoort S.J., Tan S.C., Mijnheer G., de Roock S., Vastert S.J., Nieuwenhuis E.E., van Wijk F., Prakken B.J., Creyghton M.P., Coffer P.J., Mokry M., van Loosdregt J. Inhibition of Super-Enhancer Activity in Autoinflammatory Site-Derived T Cells Reduces Disease-Associated Gene Expression. Cell Rep. 2015 Sep 29;12(12):1986-96. 

Vermunt, M.W., Reinink, P., Korving J., de Bruijn, E., Creyghton, P.M., Basak, O., Geeven, G., Toonen, P.W., Lansu, N., Meunier, C., Heesch, S., Netherlands Brain Bank; Clevers, H., de Laat, W., Cuppen, E. and Creyghton M.P.. Large scale identification of co-regulated enhancer networks in the adult human brain. Cell Rep 2014 Oct 23; 9(2):1-13. 

Welstead G.G., Creyghton, M.P., Bilodeau S., Cheng A.W., Markoulaki S., Young R.A., Jaenisch R.  X-linked H3K27me3 demethylase Utx is required for embryonic development in a sex-specific manner. Proc. Natl. Acad. Sci. USA. 2012 Aug 7; 109(32):13004-9.

Carey B.W., Markoulaki S., Hanna, J., Faddah D.A., Buganim Y, Kim J, Ganz K, Steine E.J., Cassady J.P., Creyghton, M.P., Welstead G.G., Gao Q, Jaenisch R.  Reprogramming factor stoichiometry influences the epigenetic state and biological properties of induced pluripotent stem cells. Cell Stem Cell. 2011 Dec 2; 9(6):588-98.

Creyghton, M.P., Cheng A.W., Welstead G.G., Kooistra T., Carey B.W., Steine E.J., Hanna, J., Lodato, M.A., Frampton G.M., Sharp P.A., Boyer L.A., Young, R.A., Jaenisch R.  Histone H3K27ac separates active from poised enhancers and predicts developmental state. Proc. Natl. Acad. Sci. USA. 2010 Dec 14; 107(50):21931-6.

Hanna, J., Saha K., Pando B., van Zon B, Lengner, C.J., Creyghton, M.P., van Oudenaarden A.,  Jaenisch, R. Direct reprogramming is a stochastic process amenable to acceleration. Nature 2009 Dec 3; 462(7273): 595-601.

Creyghton, M.P., Markoulaki, S., Levine, S., Hanna, J., Lodato, M.A., Sha, K., Young, R.A., Jaenisch, R. & Boyer, L.A.  H2AZ if enriched at polycomb complex target genes in ES cells and is necessary for lineage commitment. Cell 2008 135, 649-661.

Hanna, J., Markoulaki, S., Schorderet, P., Carey, B.W., Beard, C., Wernig, M., Creyghton, M.P., Steine, E.J., Cassady, J.P., Foreman, R., Lengner, C.J., Dausman, J.A. & Jaenisch, R. Direct reprogramming of terminally differentiated mature B lymphocytes to pluripotency. Cell 2008 133, 250-264.