Contact
Biography
1999-2018 Professor of Genetics, Genetics, Biology, Life Sciences, Molecular Cell & Developmental Biology, University of Nottingham
1998-1999 Reader in Molecular Genetics, Dept. of Medicine, UCL, London
1995-1999 Wellcome Trust Europ. Senior Res. Fellow, Dept. of Medicine, UCL, London
1989-1995 Head of Dev. Haematology Unit, Max-Delbrück-Laboratory, Max-Planck-Society, Cologne
1987-1989 Post-doctoral position, Prof Bob Phillips, University of Toronto
1985-1987 Post-doctoral position, Prof Klaus Rajewsky, University of Cologne
1996 Habilitation (venia legendi) in Genetics, University of Cologne
1985 PhD Genetics/Immunology, Prof Klaus Rajewsky, University of Cologne
1981 Diploma in Biology/Immunology, Prof Klaus Rajewsky, University of Cologne
1976-1980 Biology UG study, University of Cologne
Research Summary
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). 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).
https://scholar.google.co.uk/citations?user=JT6mspYAAAAJ&hl=en
- Marc Hotfilder, Diplom Biol., Universität zu Köln (1991)
Identifizierung und Charakterisierung von Genen, die entwicklungsspezifisch von hämatopoetischen Stammzellen ausgeprägt werden.
- Betina Marquardt, Diplom Biol., Universität zu Köln (1991)
Substitution des IgH-Intron-Enhancers durch den Igk-Intron Enhancer bzw. den Polyoma-Enhancer mittels homologer Rekombination.
- Ingeborg van Crüchten, Diplom Biol., Universität zu Köln (1993)
Untersuchung der entwicklungsspezifischen Expression von dnHLH-Genen in B-Zellen der Maus.
- Matthias Serwe, Dr rer nat, Universität zu Köln (1993)
Funktionelle Analyse des Immunglobulin-Intron-Enhancers der schweren Kette während der B-Zellentwicklung in vivo.
- Elisabeth Rüpping, Dr rer nat, Universität zu Köln (1994)
Gezielte Mutagenese und funktionelle Analyse des bHLH-Proteins lyl-1 in vivo.
- Veit Riechmann, Staatsexamen, Universität zu Köln (1995)
Identifizierung und Charakterisierung des neuen dnHLH-kodierenden Gens Id4 in der Maus.
- Marc Hotfilder, Dr rer nat, Universität zu Köln (1996)
Isolierung und molekulare Charaktersisierung neuer Mausgene, die im Verlauf der Entwicklung hämatopoetischer Zellen differentiell ausgeprägt werden.
- Ingeborg van Crüchten, Dr rer nat, Universität zu Köln (1997)
Molekulare Analyse und Mutagenese der dnHLH Gene Id2 und Id4.
- Maria Mirotsou, PhD, University College London (2001)
Functional analysis of dominant negative helix-loop-helix regulator Id4 in transgenic mice utilising the Cre/loxP site-specific recombination system.
- Lynn Bedford, PhD, University College London (2002)
Key functions for Id4 in gliogenesis and Id2 in spermatogenesis discovered by the analysis of knockout mice.
- Emerson R. King, PhD, University College London (2002)
Analysis of the lyl-1 null mutant mouse - a possible role in haematopoietic progenitor cell mobilisation.
- Emma Heath, PhD, University College London (2003)
Functional analysis of def-3, a novel dynamic nuclear RNA-binding protein.
- Konstantinos Mavrakis, PhD, The University of Nottingham (2003)
Functional analysis of DEF6 and def8 revealed DEF6 as a novel activator of Rac, Cdc42 and Rho GTPases regulating cell morphology.
- Robert Walker, PhD, The University of Nottingham (2004)
Id4 plays a crucial role in the timing of neural differentiation.
- Joëlle Alcock, PhD, The University of Nottingham (2005)
A role for Id2 in the maintenance of sertoli and germ cell function in murine spermatogenesis.
- Paul Martin, PhD, The University of Nottingham (2007)
Analysis of DEF6, a novel guanine nucleotide exchange factor showing dynamic regulation in vitro and playing an essential role in zebrafish development.
- Santosh Patlola, MRes, The University of Nottingham (2009)
Id4 knockdown during zebrafish development revealed its functional role in neural stem cell survival.
- Katerina Goudevenou, PhD, The University of Nottingham (2010)
DEF6 acts downstream of the non-canonical Wnt signaling pathway and is required for CE movements.
- Shabana Bashir, MRes, The University of Nottingham (2010)
Role of Id4 in neural stem cell fate during early zebrafish development.
- Wai Ho Shuen, MRes, The University of Nottingham (2010)
Molecular evolution of def6/swap70 gene family and functional analysis of swap70 in zebrafish embryogenesis.
- Taina Theodore, MRes, The University of Nottingham (2011)
Structure function analysis of the DEF6 protein.
- Tamilvendhan Dhanaseelan, MRes, The University of Nottingham (2011)
Role of Id4 in neural stem cell development in zebrafish.
- Nathan Czyzewicz, MRes, The University of Nottingham (2011)
A structure-function study of DEF6 in Jurkat and COS-7 cell lines.
- Fiona Hey, PhD, The University of Nottingham (2011)
DEF6 is phosphorylated by the Tec-family kinase ITK and forms inducible cytoplasmic granules.
- Selam Aman, MRes, The University of Nottingham (2013)
The role of swap70 protein during zebrafish embryogenesis.
- Anwesha Das, MRes, The University of Nottingham (2013)
Site-directed mutagenesis and functional analysis of DEF6 mutant proteins in COS-7 cells.
- Madhuparna Ganguly, MRes, The University of Nottingham (2013)
Role of Id4 protein in the fate of neural stem cells using zebrafish as a model system.
- Amanda Simmonds, MRes, The University of Nottingham (2013)
Id2 protein function in zebrafish neural stem cell fate.
- Urvi Thacker, MRes, The University of Nottingham (2013)
The investigation of relationship between DEF6 and mRNA translation in T Cells.
- Xiaoou Xu, PhD, The University of Nottingham (2014)
Swap70b acts downstream of Wnt11 signaling to regulate zebrafish convergence and extension cell movements.
- Tamilvendhan Dhanaseelan, PhD, The University of Nottingham (2015)
TALEN-mediated site-directed mutagenesis of HLH proteins lyl1 and Id4 to reveal their role in haematopoietic and neural stem cell fate.
- Kerry Remon, PhD, The University of Nottingham (2016)
Def6 aggregation is linked to active translation and mRNA turnover in T cells.
- Elif Naz Girayer, MRes, University of Nottingham (2017)
Id4 functional analysis during neurogenesis using zebrafish as a model system.
- Huaitao Cheng, PhD, University of Nottingham (2017)
Structure-function relationship of DEF6.
- Maha Alsayegh, PhD, University of Nottingham (2017)
DEF6 is associated with the translational initiation regulating protein synthesis of eIF4E, 4E-T and PABP and colocalises with eIF4E and PABP in the immunological synapse.
- Deniz Akdeniz, PhD, University of Nottingham (2018)