People

Professor Shaun Cowley

Professor of Molecular Biology

School/Department: Molecular Cell Biology, Department of

Telephone: +44 (0)116 229 7098

Email: smc57@leicester.ac.uk

Profile

2017 Promoted to Professor University of Leicester UK

2013 - 2017 Promoted to Reader University of Leicester UK

2012 - 2019 MRC Senior non-Clinical Fellow University of Leicester UK

2007 - 2011 MRC Career Development Fellow University of Leicester UK 2007 Awarded Lectureship University of Leicester UK

2004 - 2006 Senior Research Associate Wellcome Trust Sanger Institute Hinxton UK Allan Bradley’s lab

1999 - 2004 Postdoctoral Research Fellow Fred Hutchinson Cancer Research Center USA Robert N Eisenman’s lab

1994 - 1998 PhD Student Imperial Cancer Research Fund (via UCL) UK Malcolm Parker’s lab

1991 - 1994 Undergraduate Student University of Birmingham UK Final year project: Steve Busby’s lab 

Research

My group studies the regulation of gene expression by histone modifying enzymes. Histones make up approximately half the mass of the chromosome and so any process which requires access to the DNA (transcription DNA synthesis DNA repair etc.) has to collaborate with histone modifying/remodelling machinery to gain entry. Our work has focussed on the histone deacetylase (HDAC) family principally the highly related class-1 HDACs HDAC1 and 2 (~82% identical). HDAC1/2 are ubiquitous long lived proteins which regulate transcription as the catalytic core of 3 major multi-protein co-repressor complexes: Sin3 NuRD and CoREST. We study their function using unique conditional knock-out embryonic stem cells and transgenic mice generated in the lab.

Publications

(0) https://scholar.google.co.uk/citations?hl=en&user=YAq8C9cAAAAJ&view_op=list_works

Turnbull RE, Fairall L, Saleh A, Kelsall E, Morris KL, Ragan TJ, Savva CG, Chandru A, Millard CJ, Makarova OV, Smith CJ, Roseman AM, Fry AM, Cowley SM and Schwabe JWR.
The MiDAC histone deacetylase complex is essential for embryonic development and has a unique multivalent structure. Nat Commun. 2020 Jun 26;11(1):3252. doi: 10.1038/s41467-020-17078-8.

Smalley JP, Adams GE, Millard CJ, Song Y, Norris JKS, Schwabe JWR, Cowley SM, Hodgkinson JT. PROTAC-mediated degradation of class I histone deacetylase enzymes in corepressor complexes. Chem Commun (Camb). 2020 Apr 21;56(32):4476-4479. doi: 10.1039/d0cc01485k. 

Acetylation & Co: an expanding repertoire of histone acylations regulates chromatin and transcription. Barnes CE, English DM, Cowley SM.  Essays Biochem. 2019 Apr 23;63(1):97-107.

Sin3A recruits Tet1 to the PAH1 domain via a highly conserved Sin3-Interaction Domain.
Chandru A, Bate N, Vuister GW, Cowley SM.  Sci Rep. 2018 Oct 2;8(1):14689.

Histone deacetylase (HDAC) 1 and 2 complexes regulate both histone acetylation and crotonylation in vivo.  Kelly RDW, Chandru A, Watson PJ, Song Y, Blades M, Robertson NS, Jamieson AG, Schwabe JWR, Cowley SM.  Sci Rep. 2018 Oct 2;8(1):14690.

HDAC1 and HDAC2 Modulate TGF-β Signaling during Endothelial-to-Hematopoietic Transition. Thambyrajah R, Fadlullah MZH, Proffitt M, Patel R, Cowley SM, Kouskoff V, Lacaud G. Stem Cell Reports. 2018 Apr 10;10(4):1369-1383.

Simandi Z, Horvath A, Wright LC, Cuaranta-Monroy I, De Luca I, Karolyi K, Sauer S, Deleuze JF, Gudas LJ, Cowley SM, Nagy L.  OCT4 Acts as an Integrator of Pluripotency and Signal-Induced Differentiation. Mol Cell. 2016 Aug 18;63(4):647-61

Watson PJ, Millard CJ, Riley AM, Robertson NS, Wright LC, Godage HY, Cowley SM, Jamieson AG, Potter BV, Schwabe JW.  Insights into the activation mechanism of class I HDAC complexes by inositol phosphates. Nat Commun. 2016 Apr 25;7:11262.

Jamaladdin S, Kelly RD, O'Regan L, Dovey OM, Hodson GE, Millard CJ, Portolano N, Fry AM, Schwabe JW, Cowley SM.  Histone deacetylase (HDAC) 1 and 2 are essential for accurate cell division and the pluripotency of embryonic stem cells. Proc Natl Acad Sci U S A 2014 111:27 9840-9845

Millard CJ, Watson PJ, Celardo I, Gordiyenko Y, Cowley SM, Robinson CV, Fairall L, Schwabe JW. Class I HDACs share a common mechanism of regulation by inositol phosphates. Mol Cell. 2013 Jul 11;51(1):57-67

Dovey OM, Foster CT, Conte N, Edwards SA, Edwards JM, Singh R, Vassiliou G, Bradley A, Cowley SM. Histone deacetylase 1 and 2 are essential for normal T-cell development and genomic stability in mice.  Blood.  2013 vol. 121 no. 8 1335-1344

Whyte, AA, Bilodeau S, Orlando DA, Hoke HA, Frampton GM, Foster CT, Cowley SM and Young RA. Enhancer decommissioning by LSDD1 during embryonic stem cell differentiation.  Nature. 2012. FEB 9; 482: 221-225

Foster CT, Dovey OM, Lezina L, Luo JL, Gant TW, Barlev N, Bradley A and Cowley SM.  Lysine Specific Demethylase 1 (LSD1) Regulates the Embryonic Transcriptome and CoREST Stability.  Mol Cell Biol. 2010 Oct;30(20):4851-63.

Dovey OM, Foster CT and Cowley SM.  Histone Deacetylase 1 (HDAC1), but not HDAC2, controls embryonic stem cell differentiation.  Proc Natl Acad Sci U S A. 2010 May4;107(18):8242-8247.

Supervision

My lab has an active PhD community. I currently have 8 PhD students working on a range of projects around the regulation of gene expression by histone deacetylase complexes. We are developing new new cell lines genetic tools and PROTAC small molecules to answer question about how diverse class-I HDAC complexes regulate transcription in stem cells and cancer.

Teaching

I am the convenor for BS3010 - Regulation of gene expression and medical relevance. I also contribute lectures and tutorials to BS1030 BS2091 BS2092 and the CCMB MSc course.

Press and media

Gene regulation epigenetics HDAC enzymes and stem cells.

Activities

Member - BBSRC Panel C (2021 - 2024)

Awards

2016 Frank and Katherine May lecture prize

2012 MRC Senior non-clinical Fellowship

2007 MRC Career Development Award

2003 Alan Wolffe Memorial Prize awarded by the Rett Syndrome Research Foundation 

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