Victor Tybulewicz

Immune Cell Biology Laboratory

My group is interested in signal transduction in B and T cells, from the antigen, chemokine and cytokine receptors, as well as integrins. Signals from these receptors play critical roles in B and T cell development, activation, migration, survival and death.

We are studying how signalling pathways control these processes, using gene targeting in ES cells, protein biochemistry, imaging, RNAi screens and structural biology. For a number of years we have focused on the following signalling proteins: Vav1, Syk and Rac1 and Rac2. Current research interests include pathways controlling T cell migration and adhesion, B cell survival, the biology of memory B cells and the function of long non-coding RNAs (lncRNAs) in lymphocyte biology.

Genetics of Down syndrome

Trisomy of human chromosome 21 (Hsa21) occurs in around one in 750 live births, and the resulting gene dosage imbalance gives rise to Down syndrome (DS), the most commonly known genetic form of mental retardation. In collaboration with Professor Elizabeth Fisher (Institute of Neurology, UCL) we are interested in identifying dosage sensitive genes on Hsa21 which, when present in three copies, cause the many different phenotypes seen in DS. We are addressing this using mouse models. We have created a novel mouse strain termed Tc1 which carries a freely segregating copy of Hsa21, and which shows defects in memory, synaptic plasticity, heart development, angiogenesis and in the craniofacial skeleton.

Selected publications

Tarakhovsky, A., M. Turner, S. Schaal, P.J. Mee, L.P. Duddy, K. Rajewsky, and V.L.J. Tybulewicz. (1995) Defective antigen receptor-mediated proliferation of B and T cells in the absence of Vav. Nature 374, 467-470

Turner M, Mee PJ, Costello PS, Williams O, Price AA, Duddy LP, Furlong MT, Geahlen RL, Tybulewicz VL. (1995) Perinatal lethality and blocked B-cell development in mice lacking the tyrosine kinase Syk. Nature 378, 298-302

Walmsley MJ, Ooi SK, Reynolds LF, Smith SH, Ruf S, Mathiot A, Vanes L, Williams DA, Cancro MP, Tybulewicz VL. (2003) Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science 302(5644), 459-62

O'Doherty, A; Ruf, S; Mulligan, C; Hildreth, V; Errington, ML; Cooke, S; Sesay, A; Modino, S; Vanes, L; Hernandez, D; Linehan, JM; Sharpe, PT; Brandner, S; Bliss, TVP; Henderson, DJ; Nizetic, D; Tybulewicz, VLJ and Fisher, EMC (2005) An aneuploid mouse strain carrying human chromosome 21 with Down syndrome phenotypes. Science 309, 2033-2037

Saveliev, A; Vanes, L; Ksionda, O; Rapley, J; Smerdon, SJ; Rittinger, K and Tybulewicz, VLJ (2009) Function of the nucleotide exchange activity of Vav1 in T cell development and activation. Science Signaling 2, ra83 

Henderson, RB; Grys, K; Vehlow, A; de Bettignies, C; Zachacz, A; Henley, T; Turner, M; Batista, F and Tybulewicz, VLJ (2010) A novel Rac-dependent checkpoint in B cell development controls entry into the splenic white pulp and cell survival. Journal of Experimental Medicine 207, 837-853

Schweighoffer, E., Vanes, L., Nys, J., Cantrell, D., McCleary, S., Smithers, N., and Tybulewicz, V. L. J. (2013). The BAFF receptor transduces survival signals by co-opting the B cell antigen receptor signaling pathway. Immunity, 38, 475-488.

Victor Tybulewicz

victor.t@crick.ac.uk
+44 (0)20 379 61612

  • Qualifications and history
  • 1984 PhD MRC Laboratory of Molecular Biology, Cambridge, UK
  • 1986-1991 Postdoctoral fellow, Whitehead Institute, MIT, Cambridge, MA, USA
  • 1991-2015 Group Leader, Medical Research Council National Institute for Medical Research, London, UK
  • 2015 Group Leader, the Francis Crick Institute, London, UK