Shaun M. Cowley

Personal Details

Shaun CowleyProfessor of Molecular Biology
Shaun Cowley

DepartmentMolecular and Cell Biology
Telephone: +44 (0)116 2297098
Emailsmc57@le.ac.uk
Address: Lancaster Rd, LE1 7HB
Web Links:

Biography

  • (2017 –)   Professor of Molecular Biology, University of Leicester, UK
  • (2013 – 2017) 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
  • (1999 – 2004) Postdoctoral Research Fellow, Fred Hutchinson Cancer Research Center, USA
  • (1994 – 1998) PhD Student Imperial Cancer Research Fund (via UCL), UK
  • (1991 – 1994) Undergraduate Student, University of Birmingham, UK

Teaching

  • I lecture and give tutorials on the principles of transcriptional regulation and epigenetics to 2nd and 3rd year students. My lab also hosts 3rd year and MSc project students to study the role of HDAC enzymes in stem cell differentiation, cell progression and gene regulation.

Publications

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

  1. 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
  2. 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.
  3. Thambyrajah R, Mazan M, Patel R, Moignard V, Stefanska M, Marinopoulou E, Li Y, Lancrin C, Clapes T, Möröy T, Robin C, Miller C, Cowley S, Göttgens B, Kouskoff V, Lacaud G. GFI1 proteins orchestrate the emergence of haematopoietic stem cells through recruitment of LSD1. Nat Cell Biol. 2016 18(1):21-32
  4. 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
  5. 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
  6. Kelly RDW and Cowley SM. The physiological roles of histone deacetylase (HDAC) 1 and 2: complex co-stars with multiple leading parts. Biochem Soc Trans. 2013 Jun 1;41(3):741-9
  7. 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
  8. 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
  9. 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.
  10. 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.
  11. Cowley SM, Iritani BM, Mendrysa SM, Xu T, Cheng PF, Yada JJ, Liggit DH and Eisenman RN. The mSin3A chromatin-modifying complex is essential for embryogenesis and T-cell development. Mol Cell Biol. 2005 Aug;25(16):6990-7004.
  12. Swanson KA, Knoepfler PS, Huang K, Kang RS, Cowley SM, Laherty CD, Eisenman RN, Radhakrishnan I. HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations. Nat Struct Mol Biol. 2004 Aug;11(8):738-46.
  13. Cowley SM, Kang RS, Frangioni JV, Yada JJ, DeGrand AM, Radhakrishnan I, Eisenman RN. Functional analysis of the Mad1-mSin3A repressor-corepressor interaction reveals determinants of specificity, affinity, and transcriptional response. Mol Cell Biol. 2004 Apr;24(7):2698-709

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. This has both an academic purpose, in unravelling the processes of gene expression, and relevance to a wide range of acquired and inherited human diseases, including cancer, which can be treated with HDAC inhibitors. At present, my group consists of two postdocs, 4 PhD students and one technician.

Supervision

I have successfully supervised 7 PhD students (100% submission on-time), the first of whom won the College Prize for best PhD thesis, all graduated with at least one publication.

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    Department of Molecular and Cell Biology

    T: +44(0)116 229 7038
    E: MolCellBiol@le.ac.uk

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