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Research groups

Cell Cycle & Epigenetics

Team Leader:

Prof N. Shaun B. Thomas
Professor of Blood Cell Biology
E-mail: nicholas.s.thomas@kcl.ac.uk
Tel: 0207 848 5818 or 5808
Fax: 0207 848 5902

Research Focus:

Our work has three main objectives:

  1. Cell cycle control in normal haemopoiesis: Defining the molecular mechanisms that regulate the transition of normal haemopoietic cells from a quiescent state into the cell cycle. Determining to what extent such mechanisms are integrated with regulation of cell size, differentiation/activation and apoptotic programmes.
  2. Epigenetic control of gene expression in normal haemopoiesis: The role of CpG methylation and histone code in regulating gene expression.
  3. Haemopoietic diseases: Defining cell cycle and epigenetic abnormalities in MDS and myeloid leukaemias and the consequences on proliferation, differentiation and apoptosis.

The projects that investigate these objectives fall into two categories:

  1. Systems Biology analysis of nuclear protein interaction networks and
  2. Genome-wide analyses of epigenetic marks

Funding:

Principal Investigator:
  • Leukaemia and Lymphoma Research (LLR) (PI: Thomas (at KCL); Chronis & Plath (UCLA)) Non-clinical Fellowship Re-programming haemopoietic cells. 2010- 30th June, 2014.
  • British Society for Haematology (BSH) pilot grant (PI: Thomas) Protein interaction network of normal human cells. 2011- 31st May, 2014.
  • BBSRC (PI: Thomas; Co-I: Ford).  TET protein function in conversion of 5mC to 5hmC during cell cycle entry. 1st February, 2013-31st January, 2016.
  • Leukaemia and Lymphoma Research (LLR) Gordon Piller PhD studentship (4 yrs). (PI: Thomas; Co-I: Fraternali) Protein interaction abnormalities in leukaemia: patient-specific genetic variation and drug repositioning. 1st October, 2013- 30th September, 2017.
  • Leukaemia and Lymphoma Research (LLR) (PI: Thomas) (MODTHSR) Identifying nuclear protein interaction network changes during entry into the cell cycle. 1st June, 2013-31st May, 2016.
Co-Investigator:
  • LLR Programme Grant (PI: Mufti; Co-I: Thomas, Farzaneh, Kordasti, Marsh; Bonnet (CR-UK)) Immune dysregulation in bone marrow failure syndromes: implications for pathogenesis and clonal evolution.  2010-2014.
  • KCL JRC PhD Studentship (PI: Kordasti; Co-I: Thomas) How cells work: predicting functionally important proteins in human cells. 7th January, 2013- 6th January, 2016.
  • Research and Innovation Centre - Fondazione Edmund Mach, Italy. PhD Studentship (PI: Attila Csikasz-Nagy, Italy; Co-I: Thomas) Systems level understanding of cell size regulation. 1st April, 2013-31st March, 2016.

Selected Publications:

  1. Lea, N.C., Orr, S.J., Stoeber, K., Williams, G.H., Lam, E. W-. F., Ibrahim, M.A.A., Mufti, G.J. and Thomas, N.S.B. (2003) Commitment point during G0→G1 that controls entry into the cell cycle Molecular Cell Biology 23, 2351-2361
  2. Mohamedali, A., Soeiro, Lea, N.C., I., Glassford, J., Banerji, L., Mufti, G.J., Lam, E.W-F. and Thomas, N.S.B. (2003) Cyclin D2 controls B-cell progenitor numbers. J. Leukocyte Biol. 74,1141-1145
  3. Raj, K., John, A., Ho, A., Chronis, C., Khan, S., Samuel, J., Pomplun, S., Thomas N.S.B., Mufti, G.J. (2007) Responses to 5 Azacytidine in MDS correlate with increased apoptosis, reduced bone marrow cellularity and an unmethylated CDKN2B promoter.  Leukemia Sep;21(9):1937-44.
  4. Smith, A.E., Chronis, C., Christodoulakis, M., Orr, S.J., Lea, N.C., Twine, N.A., Bhinge, A., Mufti, G.J. and Thomas, N.S.B. (2009) Epigenetics of human T cells during the G0→G1 transition. Genome Research Aug; 19(8), 1325-1338
  5. Lee KC, Ouwehand I, Giannini AL, Thomas NSB, Dibb NJ, Bijlmakers MJ. (2010) Lck is a key target of imatinib and dasatinib in T-cell activation. Leukemia. 24(4):896-900
  6. Orr SJ, Gaymes TJ, Ladon D, Czepulkowski B, Wang R, Chronis C, Mufti GJ, Marcotte, EM and Thomas NSB. (2010) Reducing MCM levels in human primary T cells during the G0→G1 transition causes genomic instability during the first cell cycle Oncogene. 29(26):3803-3814 (EPub May 2010)
  7. Carlin, L.M., Evans, R., Milewicz, H., Matthews, D.R., Fernandes, L., Levitt, J., Keppler, M.D., Coolen, T., Barber, P., Vojnovic, B., Suhling, K., Fraternali, F., Ameer-Beg, S., Thomas, N.S.B. and Ng, T. (2011) A Targeted siRNA Screen Identifies Regulators of Cdc42 Activity at the Natural Killer Cell Immunological Synapse. Science Signaling Nov 29;4(201):ra81.
  8. Orr, S.J., Boutz, D.R., Wang, R., Chronis, C., Lea, N.C., Thayaparan, T., Hamilton, E., Milewicz, H., Blanc, E., Mufti, G.J., Marcotte, E.M., and Thomas, N.S.B. (2012) Proteomic and protein interaction network analysis of human T lymphocytes during cell cycle entry. Mol Systems Biol. Mar 13;8:573. doi: 10.1038/msb.2012.5
  9. Marson CM, Matthews CJ, Yiannaki E, Atkinson SJ, Soden PE, Shukla L, Lamadema N, Thomas NSB. (2013) Discovery of potent, isoform-selective inhibitors of histone deacetylase containing chiral heterocyclic capping groups and a N-(2-aminophenyl)benzamide binding unit. J Med Chem. Aug 8;56(15):6156-74. doi: 10.1021/jm400634n. Epub 2013 Jul 23.
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