Victor Tybulewicz group
Signal transduction from the antigen receptors of B and T cells
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 these processes, using gene targeting in ES cells, protein biochemistry, imaging, RNAi screens, and structural biology. Over the last few years we have focused on the following signalling proteins: Vav1, Syk and Rac1 and Rac2.
Mouse models of Down syndrome
Trisomy of human chromosome 21 (Hsa21) occurs in ∼1 in 750 live births, and the resulting gene dosage imbalance gives rise to Down syndrome (DS), the most common known genetic form of mental retardation. In collaboration with Prof. 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. More on mouse models of Down syndrome
- 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 PubMed abstract
- 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 PubMed abstract
- 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 PubMed abstract
- 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 PubMed abstract
- 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 PubMed abstract
- 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 [Epub ahead of print], PubMed abstract
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