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Wellcome - MRC Cambridge Stem Cell Institute

 

George Vassiliou 2020Professor George Vassiliou

Leukaemic haemopoietic stem cells

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Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

                               Departmental Affiliation: Haematology

 

Biography 

George Vassiliou is Professor of Haematological Medicine at the University of Cambridge, Cancer Research UK Senior Fellow and Consultant Haematologist at Cambridge University Hospitals. He studied Medicine at the Royal London Hospital and trained as a Haematologist in London and Cambridge. He obtained his PhD from the University of Cambridge in 2005 and went on to investigate the pathogenesis of acute myeloid leukaemia as a Cancer Research UK Clinician Scientist in Allan Bradley’s lab at the Wellcome Sanger Institute.  He became a Wellcome Senior Fellow and a member of faculty at the Sanger Institute in 2011 and moved to the Cambridge Stem Cell Institute in 2019. 

 

Funding

Cancer Research UK, Wellcome, European Research Council, Leukaemia Lymphoma Society, Rising Tide Foundation for Clinical Cancer Research, Kay Kendall Leukaemia Fund, Bloodwise, EMBO and the NIH-OxCam Scholars Program.

 

Vassiliou Research 2020

 

Research       

The Vassiliou Group seeks to understand the cell-autonomous and cell-non-autonomous processes involved in transformation of normal to leukaemic haemopoietic stem cells and to identify genetic vulnerabilities of myeloid malignancies that can be exploited as targets of novel anti-leukaemic therapies. 

To achieve these aims the group uses three main approaches: 

  • Application of genetic screens to identify and investigate genetic vulnerabilities of acute myeloid leukaemia and related cancers in order to develop new therapeutic approaches
  • Generation and study of bespoke mouse models of somatic mutation drivers of myeloid malignancies, in order to define their molecular, genomic and phenotypic effects on haemopoietic stem and progenitor cells
  • Detection and tracking of the evolution of clonal haematopoiesis in healthy individuals, in order to understand the factors involved in leukaemic progression and develop new approaches for early detection.

 

 

Group Members

Clea Barcena, Aristi Damaskou, Monika Dudek, Margaret Fabre, Malgorzata Gozdecka, Muxin Gu, Sharon Liu, Matthew MacLoughlin, Suruchi Pacharne, Pedro Quiros, Justyna Rak, Stephanie Rogers, Thomas Sheahan, Giampiero Valenzano, Meng Wang

 

Plain English

Blood stem cells live in the bone marrow and are responsible for the production of the cells of the blood and the immune system. Like all cells, blood stem cells accumulate random DNA mutations with time in every one of us. Unfortunately, in some people these changes affect genes that make the stem cells grow uncontrollably leading to the development of Acute Myeloid Leukaemia (AML), an aggressive cancer that kills more than 7 out of 10 sufferers. Our group investigates many aspects of AML from how it develops, how we can identify people at risk and how gene mutations change AML cells to make them grow abnormally. Importantly, we have also developed approaches to identify the genetic "weaknesses" of AML in order to develop new treatments against this and related cancers.

 

Key Publications

  1. Fabre, M. A., McKerrell, T., Zwiebel, M., Vijayabaskar, M. S., Park, N., Wells, P. M., Rad, R., Deloukas, P., Small, K., Steves, C. J. & Vassiliou, G. S. Concordance for clonal hematopoiesis is limited in elderly twins. Blood 135, 269-273, doi:10.1182/blood.2019001807 (2020).
  2. Uckelmann, H.J., Kim, S.M., Giovinazzo, H., Hatton, C., Gadrey, J., Krivtsov, A.V., Rücker, F.G., McGeehan, G.M., Levine, R.L., Bullinger, L., Vassiliou, G.S. and Armstrong, S.A. MLL-Menin inhibition reverses pre-leukemic progenitor self-renewal induced by NPM1c mutations. Science 367, 6477 (2020).
  3. Tzelepis, K.*, De Braekeleer, E., Aspris, D. … 29 authors …Yusa, K.*, Kouzarides, T.* & Vassiliou, G. S.* SRPK1 maintains acute myeloid leukemia through effects on isoform usage of epigenetic regulators including BRD4. Nature Communications, 9, 5378, doi:10.1038/s41467-018-07620-0 (2018).
  4. Abelson, S., Collord, G., Ng, S. W. K., Weissbrod, O., Mendelson Cohen, N., Niemeyer, E., Barda, N., Zuzarte, P. C., Heisler, …60 authors… Wareham, N. J., Gerstung, M.*, Dick, J. E.*, Brennan, P.*, Vassiliou, G. S.* & Shlush, L. I.* Prediction of acute myeloid leukaemia risk in healthy individuals. Nature 559, 400-404, doi:10.1038/s41586-018-0317-6 (2018).
  5. Gozdecka, M., Meduri, E., Mazan, M., Tzelepis, K., Dudek, M.,… 18 authors…, Adams, D., Vassiliou, G. S.* & Huntly, B. J. P.* UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs. Nature Genetics, doi:10.1038/s41588-018-0114-z (2018).
  6. Barbieri, I., Tzelepis, K., Pandolfini, L., … 5 authors …, Bannister, A. J., Han, N., De Braekeleer, E., Ponstingl, H., Hendrick, A., Vakoc, C. R., Vassiliou, G. S.* & Kouzarides, T.* Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control. Nature 552, 126-131, doi:10.1038/nature24678 (2017).
  7. Dovey, O. M., Cooper, J. L., Mupo, A., … 8 authors…, Rad, R., Arends, M., Wright, P., Yusa, K., Bradley, A., Varela, I. & Vassiliou, G. S. Molecular synergy underlies the co-occurrence patterns and phenotype of NPM1-mutant acute myeloid leukemia. Blood 130, 1911-1922, doi:10.1182/blood-2017-01-760595 (2017).
  8. Tzelepis, K., Koike-Yusa, H., De Braekeleer, E., … 16 authors… Ponstingl, H., McDermott, U., Saez-Rodriguez, J., Huntly, B. J., Iorio, F., Pina, C.*, Vassiliou, G. S.* & Yusa, K. A.* CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia. Cell Reports 17, 1193-1205, doi:10.1016/j.celrep.2016.09.079 (2016).
  9. McKerrell, T., Park, N., Moreno, T., Grove, C. S., Ponstingl, H., … 10 authors…  Zeggini, E., Ouwehand, W., Varela, I. & Vassiliou, G. S. Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Reports 10, 1239-1245, doi:10.1016/j.celrep.2015.02.005 (2015).
  10. Vassiliou, G. S.*, Cooper, J. L., Rad, R., Li, J., Rice, S., Uren, A., Rad, L., Ellis, P., Andrews, R., Banerjee, R., Grove, C., Wang, W., Liu, P., Wright, P., Arends, M. & Bradley, A.* Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nature Genetics 43, 470-475, doi:10.1038/ng.796 (2011).