Diplom in Biology, University of Cologne (1981) - PhD Genetics/Immunology, University of Cologne, Fellowship 'Fonds der Chemischen Industrie' (1985) - Habilitation (venia legendi) in Genetics, University of Cologne (1996) - Research Fellow in Immunology, University of Cologne (1985-1987) - Research Fellow in Haematopoiesis, Hospital For Sick Children, University of Toronto, Fellowship 'Deutsche Forschungsgemeinschaft' (1987-1989) - Head of Developmental Haematology Unit, Max-Delbrück-Laboratory, Max-Planck Society, Cologne, 'Nachwuchsförderung, Budesministerium für Bildung und Forschung', scientific award 'Bennigsen-Foerder-Preis des Landes NRW' (1989-1995) - Wellcome Trust European Senior Research Fellow, Department of Medicine, University College London (UCL), London (1995-1999) - Reader in Molecular Genetics, Department of Medicine, UCL, London (1998-1999) - Professor of Genetics and Scientific Director of the Gene Targeting & Transgenic Unit, Genetics (1999), School of Biology (2003), School of Life Sciences (2013), Molecular Cell & Developmental Biology, The University of Nottingham.
Molecular regulators of cell fate
Utilising molecular, cell biology and biochemical techniques including gain- and loss-of-function analysis in vertebrate model systems such as mice and zebrafish, we are analysing several genes to determine their functional role in cell fate and function during development and the adult.
We identified Id4 (Riechmann et al., 1994), the fourth member of the Id protein family (Norton et al., 1998) and through analysis of knockout and transgenic mouse models established that Id4 plays a crucial role in neural and glial progenitor cell proliferation and timing of differentiation (Bedford et al., 2005). In addition, we established that Id4 inhibits oligodendrocyte differentiation differentially regulating the expression and subcellular distribution of myelin gene products (Marin-Husstege et al., 2006). Several subsequent fruitful collaborations revealed that Id4 promotes osteoblast differentiation (Tokuzawa et al., 2010) and acts as tumour suppressor gene in chronic lymphocytic leukemia (CLL) (Chen et al., 2011). In addition, Id4 regulates mammary gland development by suppressing p38MAPK activity and recently it was shown that Id4 levels dictate the stem cell state in mouse spermatogonia (Helsel et al., 2017).
Lyl-1 and scl /tal-1, two related bHLH transcription factors, display highly overlapping expression patterns during cardiovascular and hematopoietic ontogeny (Giroux et al., 2007). Analysis of lyl-1/lacZ knockin mice revealed that lyl-1-deficient bone marrow cells have a reduced capacity to repopulate lymphoid and myeloid lineages (Capron et al., 2006). Importantly, either lyl1 or scl/tal1, a related bHLH transcription factor, is required for survival of adult haematopoietic stem and progenitor cells (Souroullas et al., 2009). In addition, lyl-1 activity is required for the maturation of newly formed blood vessels in adult mice (Pirot et al., 2010) and lyl-1-dificiency induces a stress erythropoiesis (Capron et al., 2011).
We discovered DEF6 (Hotfilder et al., 1999), an atypical Rho-family guanine nucleotide exchange factor (Mavrakis et al., 2004) that is predominantly expressed in T cells. DEF6 (also known as IBP or SLAT) is recruited to the immunological synapse upon T cell activation and localisation of DEF6 to the centre of the immune synapse is dependent upon ITK, a Tec-family kinase that phosphorylates DEF6 (Hey et al., 2012) and regulates the spatiotemporal organisation of components of T cell signalling pathways and Cdc42-dependent actin polymerisation. In zebrafish, def6a is required for convergent extension cell movements during zebrafish gastrulation downstream of Wnt5b signalling (Goudevenou et al., 2011).
HELSEL, A.R., YANG, Q.-E., OATLEY, M.J., LORD, T., SABLITZKY, F. and OATLEY, J.M., 2017. ID4 levels dictate the stem cell state in mouse spermatogonia. Development. 144(4), 624-634 HEY, F., CZYZEWICZ, N., JONES, P. and SABLITZKY, F., 2012. DEF6, a novel substrate for the Tec kinase ITK, contains a glutamine-rich aggregation-prone region and forms cytoplasmic granules that co-localise with P-bodies The Journal of Biological Chemistry. 287(37), 31073-31084 HUGHES, K.R., GÂNDARA, R.M.C., JAVKAR, T., SABLITZKY, F., HOCK, H., POTTEN, C.S. and MAHIDA, Y.R., 2012. Heterogeneity in histone 2B-green fluorescent protein-retaining putative small intestinal stem cells at cell position 4 and their absence in the colon. Am J Physiol Gastrointest Liver Physiol. 303(11), G1188-1201
GOUDEVENOU, K., MARTIN, P., YEH, Y-J., JONES, P. and SABLITZKY, F., 2011. Def6 is required for convergent extension movements during zebrafish gastrulation downstream of Wnt5b signaling PLoS One. 6(10), e26548
Dr Yee Heng (The University of Nottingham, UK)
Dr Jingying Zhang (Pennington Biomedical Research Center, Baton Rouge, USA)
Dr Yu-Jung (Sarah) Yeh (National Health Research Institute, Taiwan)
Maria Mirotsou (PhD 2001; post-doc Harvard, Boston, USA)
Lynn Bedford (PhD 2002; post-doc The University of Nottingham, UK)
Emerson King (PhD 2002; post-doc; Columbia, New York, USA)
Emma Heath (PhD 2003; post-doc Genetics, Cambridge, UK)
Konstantinos (Dino) Mavrakis (PhD 2003; post-doc Imperial College London, UK)
Robert Walker (PhD 2004; post-doc Developmental Biology, Sheffield, UK)
Joëlle Alcock (PhD 2005; post-doc The University of Nottingham, UK)
Paul Martin (PhD 2007)
Santosh Patlola (MRes 2009; Research Centre Borstel, Germany)
Katerina Goudevenou (PhD 2010; post-doc Imperial College London, UK)
Shabana Bashir (MRes 2010; Retroscreen Virology, London)
Wai Ho (Timothy) Shuen (MRes 2010 with distinction; PhD The University of Hong Kong, China)
Taina Theodore (MRes 2011)
Fiona Hey (PhD 2011; post-doc University of Leicester, UK)
Tamilvendhan Dhanaseelan (MRes 2011; PhD The University of Nottingham, UK)
Nathan Czyzewicz (MRes 2011 with merit; PhD The University of Nottingham, UK)
Selam Aman (MRes 2013)
Amanda Simmonds (MRes 2013 with merit; PhD The University of Nottingham, UK)
Urvi Nitin Thacker (MRes 2013 with merit; PhD Lancaster University, UK)
Madhuparna Ganguly (MRes 2013)
Anwesha Das (MRes 2013)
Xiaoou Xu (PhD 2014)
Tamilvendhan Dhanaseelan (PhD 2015; post-doc Newcastle University, UK)
Kerry Remon (nee Larkin) (PhD 2016)
Elif Naz Girayer (MRes 2017)
Senior Scientific Officer:
Dr Annemarie Kelly, Gene Targeting & Transgenic Unit (GTTU)