Greg Findlay's Research Group

Pubmed | Biography


Embryonic stem cell signalling modules

Pluripotent stem cells have the ability to differentiate into many of the specialized cell types found in the body, a discovery which has driven a huge research effort to exploit these cells therapeutically. A key decision in the stem cell life cycle is whether to remain pluripotent (self-renew), or alternatively differentiate along a specific lineage. This process is primarily controlled by extracellular signalling cues, which control cell fate by implementing specific gene expression patterns.

We use mouse embryonic stem cells as a tractable model system to understand the role of signalling networks in promoting pluripotent and differentiated states. In particular, we are interested in uncovering phosphorylation and ubiquitylation-based mechanisms that control these processes. Our research may facilitate the application of stem cells in regenerative medicine, and reveal novel therapeutic strategies for human diseases arising from stem cell dysfunction.

In our recent work, we have elucidated a novel role for the Erk5 protein kinase in suppressing the transition of embryonic stem cells from a naïve to a primed state. Erk5 also plays a critical role in ESC lineage specification by suppressing cardiac-specific genes and cardiomyocyte differentiation. We also identified an “isoform switch” which enables BET bromodomain proteins to coordinate pluripotent exit with Smad2 signalling and mesendoderm differentiation. An emerging project aims to elucidate a novel pluripotency signalling network centering upon the Rnf12 E3 ubiquitin ligase.

Findlay Lab Photo

People

Francisco Bustos | Postdoctoral Researcher
Rosalia Fernandez-Alonso | Postdoctoral Researcher
Anna Segarra Fas | PhD Rotation Student
Charles Williams | PhD Student

Selected Publications

Fernandez-Alonso, R., Davidson, L., Hukelmann, J. Zengerle, M., Prescott, A.R., Ciulli, A., Lamond, A., Sapkota, G.P. and Findlay, G.M. (2017) BRD4-BRD2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification EMBO Rep. In press
Fernandez-Alonso, R., Bustos, F., Williams, C.A.C. and Findlay, G.M. (2017) Protein Kinases in Pluripotency – Beyond the Usual Suspects. J Mol Biol. In press
Williams, C.A.C., Gray, N.S. and Findlay, G.M. (2017) A simple method to identify novel pluripotency kinases by high-throughput screening. J Vis Exp.
Williams, C. A. Fernandez-Alonso, R. Wang, J. Toth, R. Gray, N. S. Findlay, G. M.
(2016) Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity Cell Rep 16 1820-8
Yasui, N., Findlay, G. M., Gish, G. D., Hsiung, M. S., Huang, J., Tucholska, M., Taylor, L., Smith, L., Boldridge, W. C., Koide, A., Pawson, T., Koide, S. (2014) Directed network wiring identifies a key protein interaction in embryonic stem cell differentiation Mol Cell 54 1034-1041
Findlay, G.M., Smith, M.J., Lanner, F., Hsiung, M.S., Gish, G.D., Petsalaki, E., Kaneko, T., Huang, H., Bagshaw, R.D., Ketela, T., Tucholska, M., Taylor, L., Bowtell, D.D., Moffat, J., Ikura, M., Li, S.C., Sidhu, S.S., Rossant, J. and Pawson, T. (2013) The binding properties of the Sos1/Grb2 complex define timing and selectivity in stem cell lineage commitment. Cell. 152(5) 1008-20