University position:Professor of Molecular Haematology
Research themes:Stem Cell, Cancer
Description of research:
The long term research goal of the Göttgens group is to decipher the molecular hierarchy of regulatory networks responsible for blood stem cell and endothelial development. To this end, the group uses complementary state-of-the-art approaches including embryonic stem cell and transgenic assays, bioinformatics, high throughput sequencing and mathematical modelling. The cumulative output of more than 50 research papers over the last 5 years has been the development of the most comprehensive network model for any adult stem cell type with over 40 transcription factors and more than 100 in vivo validated direct functional interactions.
This integrated approach has resulted in the discovery of previously unrecognised combinatorial interactions between key regulators of blood stem cells with important implications for the transcriptional control of stem cell development and differentiation.
The importance of transcriptional control in both normal and leukaemic cells is underlined by the large number of transcription factor genes that cause leukaemia when disrupted or mutated. Future work will address how transcriptional programmes are perturbed in specific subtypes of leukaemia and may thus open up new avenues for the development of targeted therapies.
Further details can be found at http://hscl.cimr.cam.ac.uk/
Conny Bonifer (Birmingham)
Georges Lacaud (Manchester)
Valerie Kouskoff (Manchester)
Shinichi Nishikawa (Kobe)
Marella de Bruijn (Oxford)
Sten Eirik Jacobsen (Oxford)
Anna Randi (London)
John Pimanda (Sydney)
Shai Izraeli (Tel Aviv)
- Tijssen M.R., Cvejic A., Joshi A., Hannah R.L., Ferreira R., Forrai A., Bellissimo D.C., Oram S.H., Smethurst P.A., Wilson N.K., Wang X., Ottersbach K., Stemple D.L., Green A.R., Ouwehand W.H., Göttgens B. (2011) “Genome-Wide Analysis of Simultaneous GATA1/2, RUNX1, FLI1, and SCL Binding in Megakaryocytes Identifies Hematopoietic Regulators” Dev Cell 20(5):597-609
- 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., Göttgens B. (2011) “LIF independent JAK signalling to chromatin in embryonic stem cells uncovered from an adult stem cell disease” Nature Cell Biology 13: 13-21
- 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., Göttgens B. (2010) “Combinatorial Transcriptional Control in Blood Stem/Progenitor Cells: Genome-wide Analysis of 10 major Transcriptional Regulators” Cell Stem Cell7(4):532-544
- Pimanda J.E., Ottersbach K., Knezevic K., Kinston S., Chan W.Y.I., Wilson N.K., Landry J.R., Wood A.D., Kolb-Kokocinsky A., Green A.R., Tannahill D., Lacaud G., Kouskoff V., Göttgens B. (2007) “Gata2, Fli1 and Scl form a recursively wired gene regulatory circuit in early developing blood cells” Proc. Natl. Acad. Sci. USA 104(45): 17692-17697