乐播传媒

School of Life Sciences
 

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Fred Sablitzky

Emeritus Professor of Genetics,

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Biography

1999-2018 Professor of Genetics, Genetics, Biology, Life Sciences, Molecular Cell & Developmental Biology, 乐播传媒

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-Delbr眉ck-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).

Recent Publications

  • HUAITAO CHENG and FRED SABLITZKY, 2019.
  • HUAITAO CHENG, MAHA ALSYEGH and FRED SABLITZKY, 2019.
  • TANVI JAVKAR, KEVIN R HUGHES, FRED SABLITZKY, JERZY M BEHNKE and YASHWANT R MAHIDA, 2019. Parasitology International.
  • HELSEL, A.R., YANG, Q.-E., OATLEY, M.J., LORD, T., SABLITZKY, F. and OATLEY, J.M., 2017. Development. 144(4), 624-634
  1. Marc Hotfilder, Diplom Biol., Universit盲t zu K枚ln (1991)

Identifizierung und Charakterisierung von Genen, die entwicklungsspezifisch von h盲matopoetischen Stammzellen ausgepr盲gt werden.

  1. Betina Marquardt, Diplom Biol., Universit盲t zu K枚ln (1991)

Substitution des IgH-Intron-Enhancers durch den Igk-Intron Enhancer bzw. den Polyoma-Enhancer mittels homologer Rekombination.

  1. Ingeborg van Cr眉chten, Diplom Biol., Universit盲t zu K枚ln (1993)

Untersuchung der entwicklungsspezifischen Expression von dnHLH-Genen in B-Zellen der Maus.

  1. Matthias Serwe, Dr rer nat, Universit盲t zu K枚ln (1993)

Funktionelle Analyse des Immunglobulin-Intron-Enhancers der schweren Kette w盲hrend der B-Zellentwicklung in vivo.

  1. Elisabeth R眉pping, Dr rer nat, Universit盲t zu K枚ln (1994)

Gezielte Mutagenese und funktionelle Analyse des bHLH-Proteins lyl-1 in vivo.

  1. Veit Riechmann, Staatsexamen, Universit盲t zu K枚ln (1995)

Identifizierung und Charakterisierung des neuen dnHLH-kodierenden Gens Id4 in der Maus.

  1. Marc Hotfilder, Dr rer nat, Universit盲t zu K枚ln (1996)

Isolierung und molekulare Charaktersisierung neuer Mausgene, die im Verlauf der Entwicklung h盲matopoetischer Zellen differentiell ausgepr盲gt werden.

  1. Ingeborg van Cr眉chten, Dr rer nat, Universit盲t zu K枚ln (1997)

Molekulare Analyse und Mutagenese der dnHLH Gene Id2 und Id4.

  1. 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.

  1. Lynn Bedford, PhD, University College London (2002)

Key functions for Id4 in gliogenesis and Id2 in spermatogenesis discovered by the analysis of knockout mice.

  1. Emerson R. King, PhD, University College London (2002)

Analysis of the lyl-1 null mutant mouse - a possible role in haematopoietic progenitor cell mobilisation.

  1. Emma Heath, PhD, University College London (2003)

Functional analysis of def-3, a novel dynamic nuclear RNA-binding protein.

  1. Konstantinos Mavrakis, PhD, The 乐播传媒 (2003)

Functional analysis of DEF6 and def8 revealed DEF6 as a novel activator of Rac, Cdc42 and Rho GTPases regulating cell morphology.

  1. Robert Walker, PhD, The 乐播传媒 (2004)

Id4 plays a crucial role in the timing of neural differentiation.

  1. Jo毛lle Alcock, PhD, The 乐播传媒 (2005)

A role for Id2 in the maintenance of sertoli and germ cell function in murine spermatogenesis.

  1. Paul Martin, PhD, The 乐播传媒 (2007)

Analysis of DEF6, a novel guanine nucleotide exchange factor showing dynamic regulation in vitro and playing an essential role in zebrafish development.

  1. Santosh Patlola, MRes, The 乐播传媒 (2009)

Id4 knockdown during zebrafish development revealed its functional role in neural stem cell survival.

  1. Katerina Goudevenou, PhD, The 乐播传媒 (2010)

DEF6 acts downstream of the non-canonical Wnt signaling pathway and is required for CE movements.

  1. Shabana Bashir, MRes, The 乐播传媒 (2010)

Role of Id4 in neural stem cell fate during early zebrafish development.

  1. Wai Ho Shuen, MRes, The 乐播传媒 (2010)

Molecular evolution of def6/swap70 gene family and functional analysis of swap70 in zebrafish embryogenesis.

  1. Taina Theodore, MRes, The 乐播传媒 (2011)

Structure function analysis of the DEF6 protein.

  1. Tamilvendhan Dhanaseelan, MRes, The 乐播传媒 (2011)

Role of Id4 in neural stem cell development in zebrafish.

  1. Nathan Czyzewicz, MRes, The 乐播传媒 (2011)

A structure-function study of DEF6 in Jurkat and COS-7 cell lines.

  1. Fiona Hey, PhD, The 乐播传媒 (2011)

DEF6 is phosphorylated by the Tec-family kinase ITK and forms inducible cytoplasmic granules.

  1. Selam Aman, MRes, The 乐播传媒 (2013)

The role of swap70 protein during zebrafish embryogenesis.

  1. Anwesha Das, MRes, The 乐播传媒 (2013)

Site-directed mutagenesis and functional analysis of DEF6 mutant proteins in COS-7 cells.

  1. Madhuparna Ganguly, MRes, The 乐播传媒 (2013)

Role of Id4 protein in the fate of neural stem cells using zebrafish as a model system.

  1. Amanda Simmonds, MRes, The 乐播传媒 (2013)

Id2 protein function in zebrafish neural stem cell fate.

  1. Urvi Thacker, MRes, The 乐播传媒 (2013)

The investigation of relationship between DEF6 and mRNA translation in T Cells.

  1. Xiaoou Xu, PhD, The 乐播传媒 (2014)

Swap70b acts downstream of Wnt11 signaling to regulate zebrafish convergence and extension cell movements.

  1. Tamilvendhan Dhanaseelan, PhD, The 乐播传媒 (2015)

TALEN-mediated site-directed mutagenesis of HLH proteins lyl1 and Id4 to reveal their role in haematopoietic and neural stem cell fate.

  1. Kerry Remon, PhD, The 乐播传媒 (2016)

Def6 aggregation is linked to active translation and mRNA turnover in T cells.

  1. Elif Naz Girayer, MRes, 乐播传媒 (2017)

Id4 functional analysis during neurogenesis using zebrafish as a model system.

  1. Huaitao Cheng, PhD, 乐播传媒 (2017)

Structure-function relationship of DEF6.

  1. Maha Alsayegh, PhD, 乐播传媒 (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.

  1. Deniz Akdeniz, PhD, 乐播传媒 (2018)
  • HUAITAO CHENG and FRED SABLITZKY, 2019.
  • HUAITAO CHENG, MAHA ALSYEGH and FRED SABLITZKY, 2019.
  • TANVI JAVKAR, KEVIN R HUGHES, FRED SABLITZKY, JERZY M BEHNKE and YASHWANT R MAHIDA, 2019. Parasitology International.
  • HELSEL, A.R., YANG, Q.-E., OATLEY, M.J., LORD, T., SABLITZKY, F. and OATLEY, J.M., 2017. Development. 144(4), 624-634
  • XU X, SHUEN WH, CHEN C, GOUDEVENOU K, JONES P and SABLITZKY F, 2014. Developmental biology. 386(1), 191-203
  • HUGHES, K.R., G脗NDARA, R.M.C., JAVKAR, T., SABLITZKY, F., HOCK, H., POTTEN, C.S. and MAHIDA, Y.R., 2012. Am J Physiol Gastrointest Liver Physiol. 303(11), G1188-1201
  • HEY, F., CZYZEWICZ, N., JONES, P. and SABLITZKY, F., 2012. Journal of Biological Chemistry. 287(37), 31073-31084
  • CHEN, S.-S., CLAUS, R., LUCAS, D.M., YU, L., QIAN, J., RUPPERT, A.S., WEST, D.A., WILLIAMS, K.E., JOHNSON, A.J., SABLITZKY, F., PLASS, C. and BYRD, J.C., 2011. Blood. 117(3), 862-871
  • CAPRON, C., LACOUT, C., L脡CLUSE, Y., WAGNER-BALLON, O., KAUSHIK, A.L., CRAMER-BORD脡, E., SABLITZKY, F., DUM脡NIL, D. and VAINCHENKER, W., 2011. Experimental Hematology. 39(6), 629-642
  • DONG, J, HUANG, S., CAIKOVSKI, M., JI, S., MCGRATH, A., CUSTORIO, M.G., CREIGHTON, C.J., MALIAKKAL, P., BOGOSLOVSKAIA, E., DU, Z., ZHANG, X., LEWIS, M.T., SABLITZKY, F., BRISKEN, C. and LI, Y., 2011. Development. 138, 5247-5256
  • GOUDEVENOU, K., MARTIN, P., YEH, Y-J., JONES, P. and SABLITZKY, F., 2011. PLoS One. 6(10), e26548
  • HEATH, E., SABLITZKY, F. and MORGAN, G.T., 2010. Chromosome Research. 18(8), 851-872
  • PIROT, N., DELEUZE, V., EL-HAJJ, R., DOHET, C., SABLITZKY, F., COUTTET, P., MATHIEU, D. and PINET, V., 2010. Blood. 115(25), 5270-5279
  • TOKUZAWA, Y., YAGI, K., YAMASHITA, Y., NAKACHI, Y., NIKAIDO, I., BONO, H., NINOMIYA, Y., KANESAKI-YATSUKA, Y., AKITA, M., MOTEGI, H., WAKANA, S., NODA, T., SABLITZKY, F., ARAI, S., KUROKAWA, R., FUKUDA, T., KATAGIRI, T., SCH脰NBACH, C., SUDA, T., MIZUNO, Y. and OKAZAKI, Y., 2010. PLoS Genetics. 6(7), e1001019
  • CHEN SS, CLAUS R, LUCAS DM, YU L, QIAN J, RUPPERT AS, WEST DA, WILLIAMS KE, JOHNSON AJ, SABLITZKY F, PLASS C and BYRD JC, 2010. Blood. 117(3), 862-71
  • HEATH E, SABLITZKY F and MORGAN GT, 2010. Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology. 18(8), 851-72
  • SOUROULLAS, G.P., SALMON, J.M., SABLITZKY, F., CURTIS, D.J. and GOODELL, M.A., 2009. Cell Stem Cell. 4(2), 180-186
  • CHAN, W.Y.I., FOLLOWS, G.A., LACAUD, G., PIMANDA, J.E., LANDRY, ,J.-R., KINSTON, S., KNEZEVIC, K., PILTZ, S., DONALDSON, I.J., GAMBARDELLA, L., SABLITZKY, F., GREEN, A.R., KOUSKOFF, V. and G脰TTGENS, B., 2007. Blood. 109(5), 1908-1916
  • GIROUX, S., KAUSHIK, A-L., CAPRON, C., JALIL, A., KELAIDI, C., SABLITZKY, F., DUMENIL, D., ALBAGLI, O. and GODIN, I., 2007. Gene Expression Patterns. 7(3), 215-226
  • CAPRON, C., L脡CLUSE, Y., KAUSHIK, A. L., FOUDI, A., LACOUT, C., SEKKAI, D., GODIN, I., ALBAGLI, O., POULLION, I., SVINARTCHOUK, F., SCHANZE, E., VAINCHENKER, W., SABLITZKY, F., BENNACEUR-GRISCELLI, A. and DUM脡NIL, D., 2006. Blood. 107(12), 4678-4686
  • MARIN-HUSSTEGE, M., HE, Y., LI, J., KONDO, T., SABLITZKY, F. and CASACCIA-BONNEFIL, P., 2006. Glia. 54(4), 285-296
  • GARRATT, L.C., ORTORI, C.A., TUCKER, G.A., SABLITZKY, F., BENNETT, M.J. and BARRETT, D.A., 2005. Rapid Communications in Mass Spectrometry. 19(17), 2390-2398
  • BEDFORD, L, WALKER, R, KONDO, T, VAN CRUCHTEN, I, KING, ER and SABLITZKY, F, 2005. Developmental Biology. 280(2), 386-395
  • MAVRAKIS, K.J., MCKINLAY, K.J., JONES, P. and SABLITZKY, F., 2004. Experimental Cell Research. 294(2), 335-344
  • AHMED, B.Y., CHAKRAVARTHY, S., EGGERS, R., HERMENS, W.T.J.M.C, ZHANG, J.Y., NICLOU, S.P., LEVELT, C., SABLITZKY, F., ANDERSON, P.N., LIEBERMAN, A R and VERHAAGEN, J., 2004. BMC Neuroscience. 5, 4
  • CINATO, E., MIROTSOU, M. and SABLITZKY, F., 2001. Genesis. 31(3), 118-129
  • HENG, Y M, FOX, M and SABLITZKY, F, 2000. Cytogenetics and Cell Genetics. 89(3-4), 238-9
  • DRABKIN, H. A., WEST, J. D., HOTFILDER, M., HENG, Y. M., ERICKSON, P., CALVO, R., DALMAU, J., GEMMILL, R. M. and SABLITZKY, F., 1999. Oncogene. VOL 18(NUMB 16), 2589-2598
  • HOTFILDER, M, BAXENDALE, S, CROSS, M A and SABLITZKY, F, 1999. British Journal of Haematology. 106(2), 335-44
  • SABLITZKY, F, MOORE, A, BROMLEY, M, DEED, R W, NEWTON, J S and NORTON, J D, 1998. Cell Growth & Differentiation. 9(12), 1015-24
  • BOTTARO, A, YOUNG, F, CHEN, J, SERWE, M, SABLITZKY, F and ALT, F W, 1998. International Immunology. 10(6), 799-806
  • VAN CR脺CHTEN, I, CINATO, E, FOX, M, KING, E R, NEWTON, J S, RIECHMANN, V and SABLITZKY, F, 1998. Structure, chromosomal localisation and expression of the murine dominant negative helix-loop-helix Id4 gene. Biochimica et Biophysica Acta. 1443(1-2), 55-64
  • NORTON, J D, DEED, R W, CRAGGS, G and SABLITZKY, F, 1998. Trends in Cell Biology. 8(2), 58-65
  • JAHNEN-DECHENT, W, SCHINKE, T, TRINDL, A, M脺LLER-ESTERL, W, SABLITZKY, F, KAISER, S and BLESSING, M, 1997. Journal of Biological Chemistry. 272(50), 31496-503
  • ZHANG, Y, RIESTERER, C, AYRAL, A M, SABLITZKY, F, LITTLEWOOD, T D and RETH, M, 1996. Nucleic Acids Research. 24(4), 543-8
  • RIECHMANN, V and SABLITZKY, F, 1995. Cell Growth & Differentiation. 6(7), 837-43
  • NACKEN, W, KINGSMAN, A J, KINGSMAN, S M, SABLITZKY, F and SORG, C, 1995. A homologue of the human MSS1 gene, a positive modulator of HIV-1 gene expression, is massively expressed in Xenopus oocytes. Biochimica et Biophysica Acta. 1261(2), 293-5
  • RIECHMANN, V, VAN CR脺CHTEN, I and SABLITZKY, F, 1994. Nucleic Acids Research. 22(5), 749-55
  • SABLITZKY, F, JOENSSON, J I, COHEN, B L and PHILLIPS, R A, 1993. Cell Growth & Differentiation. 4(6), 451-9
  • SERWE, M and SABLITZKY, F, 1993. EMBO Journal. 12(6), 2321-7
  • ROES, J, HUEPPI, K, RAJEWSKY, K and SABLITZKY, F, 1989. The Journal of Immunology. 142(3), 1022-6
  • HOMBACH, J, SABLITZKY, F, RAJEWSKY, K and RETH, M, 1988. Journal of Experimental Medicine. 167(2), 652-7
  • ALLEN, D, CUMANO, A, SIMON, T, SABLITZKY, F and RAJEWSKY, K, 1988. International Journal of Cancer. 3, 1-8
  • ALLEN, D, SIMON, T, SABLITZKY, F, RAJEWSKY, K and CUMANO, A, 1988. EMBO Journal. 7(7), 1995-2001
  • ALLEN, D, CUMANO, A, DILDROP, R, KOCKS, C, RAJEWSKY, K, RAJEWSKY, N, ROES, J, SABLITZKY, F and SIEKEVITZ, M, 1987. Immunological reviews.. 96, 5-22
  • SABLITZKY, F, WEISBAUM, D and RAJEWSKY, K, 1985. EMBO Journal. 4(13A), 3435-7
  • SABLITZKY, F, WILDNER, G and RAJEWSKY, K, 1985. EMBO Journal. 4(2), 345-50
  • KLEIN, S, SABLITZKY, F and RADBRUCH, A, 1984. EMBO Journal. 3(11), 2473-6
  • SABLITZKY, F and RAJEWSKY, K, 1984. EMBO Journal. 3(12), 3005-12
  • RADBRUCH, A and SABLITZKY, F, 1983. EMBO Journal. 2(11), 1929-35
  • SABLITZKY, F, RADBRUCH, A and RAJEWSKY, K, 1982. Immunological reviews.. 67, 59-72
  • BAUMHAECKEL, H, LIESEGANG, B, RADBRUCH, A, RAJEWSKY, K and SABLITZKY, F, 1982. The Journal of Immunology. 128(3), 1217-20

School of Life Sciences

乐播传媒
Medical School
Queen's Medical Centre
乐播传媒 NG7 2UH

e: life-sciences@nottingham.ac.uk
t: +44 (0)115 823 0141
f: +44 (0)115 823 0142