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Bertie Göttgens

Network control of normal and leukaemic blood stem cells

The Göttgens group uses a combination of experimental and computational approaches to study how transcription factor networks control the function of blood stem cells and how mutations that perturb such networks cause leukaemia. This integrated approach has resulted in the discovery of new combinatorial interactions between key blood stem cell regulators, as well as experimentally validated computational models for blood stem cells. Current research focuses on (i) single cell genomics of early blood development, (ii) computer models to chart the transcriptional landscape of blood stem and progenitor cell differentiation, (iii) transcriptional consequences of leukaemogenic mutations in leukaemia stem/progenitor cells, and (iv) molecular characterisation of human blood stem/progenitor cell populations used in cell and gene therapy protocols.

 

Bertie Göttgens, whose lab is based in the CIMR, is a principal investigator of the Cambridge Stem Cell Institute (SCI) and will relocate to a new SCI building in 2018. 

Key papers

Wilson NK, Kent DK, Buettner F, Shehata M, Macaulay IC, Calero-Nieto FJ, Sánchez Castillo M, Oedekoven CA, Diamanti E, Schulte R, Ponting CP, Voet T, Caldas C, Stingl J, Green AR, Theis FJ, Göttgens B. Cell Stem Cell 16, 712-724 (2015).

Moignard V., Woodhouse S., Haghverdi L., Lilly A.J., Tanaka Y., Wilkinson A.C., Buettner F., Macaulay I.C., Jawaid W., Diamanti E., Nishikawa S., Piterman N., Kouskoff V., Theis F.J., Fisher J. and Göttgens B. Decoding the Regulatory Network for Blood Development from Single-Cell Gene Expression Measurements. Nature Biotech. 33, 269-276 (2015).

Moignard, V., Macaulay, I.C., Swiers, G., Buettner ,F., Schütte, J., Calero-Nieto, F.J., Kinston, S., Joshi, A., Hannah, R., Theis, F.J., Jacobsen, S.E., de Bruijn, M.F.T. and Göttgens, B. Characterisation of transcriptional networks in blood stem and progenitor cells using high-throughput single cell gene expression analysis. Nature Cell Biol. 15, 363–372 (2013).

Griffiths, D.S., Li, J., Dawson, M.A., Trotter, M., Cheng, Y.-H., Smith, A.M., Mansfield, W., Liu, P., Kouzarides, T., Nichols, J., Bannister, A.J., Green, A.R. and Göttgens, B. LIF-independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease. Nature Cell Biol. 13, 13–21 (2011).

Wilson, N.K., Foster, S.D., Wang, X., Knezevic, K., Schütte, J., Kaimakis, P., Chilarska, P., Kinston, S., Ouwehand, W.H., Dzierzak, E., Pimanda, J.E., de Bruijn, M.F. and Göttgens, B. Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators. Cell Stem Cell 7, 532–544 (2010).

 

Bertie Göttgens

Professor of Molecular Haematology

Department: Haematology

Cambridge Stem Cell Institute

contact: bg200@cam.ac.uk

01223 336 822

Plain English

Blood stem cells ensure the constant supply of new blood cells throughout a person’s lifetime. The normal function of blood stem cells critically depends on the fine tuning of which genes should be active at any given time. Moreover, a large number of leukaemias arise, when this fine balance of gene activities is disturbed. Through our research, we want to answer the following questions: What are the mechanisms that regulate gene activities to ensure normal blood stem cell function? Can we identify new strategies to treat leukaemia by reversing the disturbed balance of gene activities? To answer these questions, we use a combination of experimental and computational approaches. This has allowed us to discover how individual regulatory genes are connected to form complex networks. Future work will investigate how perturbation of these complex networks can cause leukaemia.

Group members

Silvia Basilico · Fernando Calero · Debbie Goode · Fiona Hamey · Rebecca Hannah · Wajid Jawaid · Isabel Jimenez · Sarah Kinston · Vasilis Ladopoulos · Winnie Lau · Chee Lim Vicki Moignard · Felicia Ng · Moosa Qureshi · Yosuke Tanaka · Adam Wilkinson · Nicola Wilson · Steven Woodhouse

Funding

BBSRC

Medical Research Council

Leukaemia and Lymphoma Research

Cancer Research UK

Leukaemia and Lymphoma Society

Microsoft Research

NIHR