Dr George Vassiliou
Leukaemic haemopoietic stem cells
Laboratory: Wellcome Trust Sanger Institute. Departmental Affiliation: Haematology
George Vassiliou graduated from the Royal London Hospital Medical College in 1994, having obtained an intercalated BSc in Pharmacology with Basic Medical Sciences in 1991. He carried out his basic medical training in London and Cambridge and became a member of the Royal College of Physicians in 1997. He went on to train in Haematology at the Hammersmith and Great Ormond Street Hospitals, and received his PhD from the University of Cambridge in 2005. After completing his Haematology training in Cambridge, he became a Member of the Royal College of Pathologists in 2005 and from 2006-11 carried out a postdoctoral period in Allan Bradley’s Laboratory at the Wellcome Trust Sanger Institute, funded by a Cancer Research UK Clinician Scientist Fellowship. In 2011 he won a Wellcome Trust Senior Fellowship in Clinical Science and became a member of Faculty and Group Leader at the Sanger Institute. He joined the Faculty of the Cambridge Stem Cell Institute in 2015. Additionally, he has been an honorary Consultant Haematologist at Cambridge University Hospitals since 2006.
The Vassiliou Group studies the preclinical evolution, pathogenesis and treatment of haematological malignancies with a particular focus on acute myeloid leukaemia and its leukaemic stem cells. Recent highlights of the group’s work include the identification of distinct patterns of clonal haemopoiesis driven by leukaemia-associated mutations in healthy people, the generation of the first genome-wide catalogue of genetic vulnerabilities and therapeutic targets in acute myeloid leukaemia and the development of a novel murine model of human myelodysplastic syndromes driven by mutations in the spliceosome gene SF3B1.
Wellcome Trust, Cancer Research UK, Bloodwise, Kay Kendal Leukaemia Fund, Addenbrooke’s Charitable Trust
The Vassiliou Group seeks to understand the molecular mechanisms involved in transformation of normal to leukaemic haemopoietic stem cells and to identify their differential genetic vulnerabilities in order to develop novel anti-leukaemic therapies.
To achieve these aims the group uses three main 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
- Application of genetic screens to identify the molecular pathways involved in the transformation of HSCs (transposon mutagenesis) and the survival of leukaemic stem cells (genome-wide CRISP Cas9 screens)
- Sequencing-based approaches to detect and track the evolution of pre-clinical haemopoietic clones in haematologically normal individuals, in order to understand the factors involved in leukaemic progression.
Vijay Baskar, Etienne De Braekeleer, Grace Collord, Jonathan Cooper, Joao Dias, Oliver Dovey, Monika Dudek, Dimitris Garyfallos, Gonia Gozdecka, Suruchi Pacharne, Konstantinos Tzelepis.
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. In some unfortunate individuals these changes affect genes that make the stem cells grow uncontrollably leading to the development of Acute Myeloid Leukaemia or AML, an aggressive cancer that kills more than 7 out of 10 sufferers. Our group investigates many aspects of AML from how it develops, whether we can identify people who are at risk of developing it, how gene mutations make AML cells grow uncontrollably, how we detect the mutation in each individual AML and most importantly how to identify the "weaknesses" od AML in order to develop new treatments against this lethal cancer.
- Tzelepis, K., Koike-Yusa, H., De Braekeleer, E., Li, Y., Metzakopian, E., Dovey, O. M., Mupo, A., Grinkevich, V., Li, M., Mazan, M., Gozdecka, M., Ohnishi, S., Cooper, J., Patel, M., McKerrell, T., Chen, B., Domingues, A. F., Gallipoli, P., Teichmann, S., Ponstingl, H., McDermott, U., Saez-Rodriguez, J., Huntly, B. J., Iorio, F., Pina, C., Vassiliou, G. S. & Yusa, K. (2016) 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.
- Mupo, A., Seiler, M., Sathiaseelan, V., Pance, A., Yang, Y., Agrawal, A. A., Iorio, F., Bautista, R., Pacharne, S., Tzelepis, K., Manes, N., Wright, P., Papaemmanuil, E., Kent, D. G., Campbell, P. C., Buonamici, S., Bolli, N. & Vassiliou, G. S. Hemopoietic-specific Sf3b1-K700E knock-in mice display the splicing defect seen in human MDS but develop anemia without ring sideroblasts. Leukemia, doi:10.1038/leu.2016.251 (2016).
- McKerrell T, Vassiliou GS (2015) Aging as a driver of leukemogenesis. Science Translational Medicine 7, 306fs338. PMID:26400908
- McKerrell T, Park N, Moreno T, Grove CS, Ponstingl H, Stephens J, Understanding Society Scientific G, Crawley C, Craig J, Scott MA, Hodkinson C, Baxter J, Rad R, Forsyth DR, Quail MA, Zeggini E, Ouwehand W, Varela I, Vassiliou GS(2015) Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis. Cell Reports 10, 1239-1245 PMCID:PMC4542313
- Vassiliou G*, Cooper JL, Li J, Rad R, Rice S, Uren A, Rad L, Ellis P, Andrews R, Grove C, Banerjee R, Wright P, Arends M, Bradley A*. Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice. Nature Genetics, 2011, May;43(5):470-5. PMCID:PMC3084174