Victor Tybulewicz

Immune Cell Biology Laboratory and Down Syndrome 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 mouse genetics, protein biochemistry, imaging, cell biology, and RNAi and CRISPR screens. Current research interests include pathways controlling B and T cell migration and adhesion, B cell survival, the biology of memory B cells and the function of long non-coding RNAs in lymphocyte biology.

BAFFR transduces survival signals via the BCR.

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 cognitive impairment. 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. To address this, we have created a large number of mouse models with duplications of different regions of the mouse genome orthologous to Hsa21. Using these novel strains, we are identifying the causative genes causing cognitive impairment, congenital heart defects, craniofacial abnormalities and neurodegeneration, and studying the underlying pathological mechanisms.

A genetic mapping panel of 9 mouse strains to find dosage-sensitive genes contributing to DS phenotypes.

Selected publications

Schweighoffer, E, Nys, J, Vanes, L, Smithers, N, Tybulewicz, VL (2017). TLR4 signals in B lymphocytes are transduced via the B cell antigen receptor and SYK.J Exp Med, 214, 1269-1280

Köchl, R, Thelen, F, Vanes, L, Brazão, TF, Fountain, K, Xie, J, Huang, C-L, Lyck, R, Stein, JV, Tybulewicz, VLJ (2016). WNK1 kinase balances T cell adhesion and migration in vivo. Nat Immunol, 17, 1075-1083

Brazão, TF, Johnson, JS, Müller, J, Heger, A, Ponting, CP, Tybulewicz, VLJ (2016). Long non-coding RNAs in B cell development and activation. Blood, 128, e10-9

Lana-Elola, E, Watson-Scales, S, Slender, A, Gibbins, D, Martineau, A, Douglas, C, Mohun, T, Fisher, EMC, Tybulewicz, VLJ (2016). Genetic dissection of Down syndrome-associated congenital heart defects using a new mouse mapping panel. eLife, pii:e11614. doi:10.7554/eLife.11614.001

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

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. J Exp Med 207, 837-853

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

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, 459-62

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

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

Victor Tybulewicz portrait

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