Greg Findlay's Research Group

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Embryonic Stem Cell Signalling in Health and Disease

Our lab applies cutting-edge chemical, genetic, proteomic and transcriptomic technologies to investigate signalling mechanisms that regulate Embryonic Stem (ES) cell biology. Using these approaches, we have uncovered a series of exciting new ES cell signalling pathways, providing key insights into regulation of stem cell maintenance, pluripotency and differentiation. The current aim of this project is to identify the mechanisms by which these pathways function to control ES cell biology. Recently, we have begun exploring how disruptions to stem cell signalling networks lead to human developmental disorders, particularly intellectual disability. A major goal of this project is to pinpoint novel signalling components that are mutated in intellectual disability syndromes, and use stem cell models to elucidate the molecular mechanisms underpinning development of these disorders in patients.

From the left: Francisco Bustos, Greg Findlay, Rosalia Fernandez-Alonso, Anna Segarra Fas, Charles Williams
From the left: Francisco Bustos, Greg Findlay, Rosalia Fernandez-Alonso, Anna Segarra Fas, Charles Williams

People

Maren Sechting | Visiting Undergraduate
Helen Brown | PhD Student
Francisco Bustos | Postdoctoral Researcher
Carmen Espejo Serrano | Wellcome Trust PhD Student
Findlay Munro | Wellcome Trust PhD Student
Anna Segarra Fas | PhD Student

Selected Publications

1   Mullin NP, Varghese J, Colby D, Richardson JM, Findlay GM, Chambers I (2020) Phosphorylation of NANOG by casein kinase I regulates embryonic stem cell self-renewal FEBS Letters
2   Bustos F, Segarra-Fas A, Nardocci G, Cassidy A, Antico O, Davidson L, Brandenburg L, Macartney TJ, Toth R, Hastie CJ, Moran J, Gourlay R, Varghese J, Soares RF, Montecino M, Findlay GM (2020) Functional Diversification of SRSF Protein Kinase to Control Ubiquitin-Dependent Neurodevelopmental Signaling Developmental Cell 55 1-19
3   Fernandez-Alonso, R., Bustos, F., Budzyk, M., Helbig, A., Hukelmann, J., Lamond, A., Petsalaki, E. and Findlay, G.M. (2020) Phosphoproteomics Identifies a Bimodal EPHA2 Receptor Switch that Promotes Embryonic Stem Cell Differentiation Nature Communications 11 1357
4   Heap, RE, Segarra Fas, A, Blain, AP, Findlay, G & Trost, M (2019) Profiling embryonic stem cell differentiation by MALDI TOF mass spectrometry: development of a reproducible and robust sample preparation workflow Analyst 144 6371-6381
5   Bustos F, Segarra-Fas A, Chaugule VK, Brandenburg L, Branigan E, Toth R, Macartney T, Knebel A, Hay RT, Walden H, Findlay GM (2018) RNF12 X-Linked Intellectual Disability Mutations Disrupt E3 Ligase Activity and Neural Differentiation. Cell Rep 23 1599-1611
6   Fernandez-Alonso R, Davidson L, Hukelmann J, Zengerle M, Prescott AR, Lamond A, Ciulli A, Sapkota GP, Findlay GM. (2017) Brd4-Brd2 isoform switching coordinates pluripotent exit and Smad2-dependent lineage specification EMBO Rep 18(7) 1108-1122
7   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. 42 1504-1520
8   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. 123 55515
9   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
10   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
11   Saliba, A. E., Vonkova, I., Ceschia, S., Findlay, G. M., Maeda, K., Tischer, C., Deghou, S., van Noort, V., Bork, P., Pawson, T., Ellenberg, J., Gavin, A. C. (2014) A quantitative liposome microarray to systematically characterize protein-lipid interactions Nat Methods 11 47-50
12   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