Vassiliou Group

George Vassiliou

Professor George Vassiliou

Leukaemic & preleukaemic haemopoietic stem cells

Email: gsv20@cam.ac.uk     |     Departmental Affiliation: Haematology

 

Research       

Plain English:

Each day humans produce more than 200 billion mature blood cells from a small number of blood stem cells, also known as haematopoietic stem cells (HSCs). HSCs are produced whilst we are still in the womb and, for the rest of our life, live in the bone marrow where the environment provides them with nutrients and signals to increase or decrease blood cell production as required by the body. However, like all cells, HSCs steadily accumulate random DNA mutations with time. Most mutations have no discernible effects, but a small minority can drive an HSC to divide and produce many copies (clones) of itself.This phenomenon, known as clonal haematopoiesis (CH), becomes very common with advancing age. Unfortunately, in some people CH progresses to a blood cancer like Acute Myeloid Leukaemia (AML) or Myelodysplastic Syndrome (MDS).

The Vassiliou Group investigates how these cancers develop, how they can identify people at risk of developing them and how they may be able to stop this from happening. In parallel, they explore how gene mutations make cells cancerous, apply genetic approaches to identify "weaknesses" of these cancerous cells and use these insights to develop new treatments against them.

Research Focus: The Vassiliou group seeks to understand the cell-autonomous and non-cell-autonomous processes involved in transformation of normal HSCs to leukaemic stem cells and to develop new therapeutic approaches to prevent and/or treat AML, MDS and related myeloid malignancies.

To achieve these aims, they use three main approaches:　

  • Application of genetic screens to identify and investigate genetic vulnerabilities of myeloid malignancies in order to develop new therapeutic approaches
  • Generation and study of bespoke mouse models of somatic mutation drivers of myeloid malignancies, to define their molecular, genomic and phenotypic effects on haemopoietic stem and progenitor cells
  • Investigation of the genetic, molecular and epidemiological basis of CH in healthy individuals, in order to predict and understand the drivers of leukaemic progression and develop new approaches for early detection and prevention of myeloid malignancies.
Photo of the Vassiliou Group members

Vassiliou Group photo

Selected Publications

  1. McLoughlin MA et al. Telomere attrition becomes an instrument for clonal selection in aging hematopoiesis and leukemogenesis.Nat Genet. 57:2215-2225 (2025).
  2. Gozdecka M et al.Mitochondrial metabolism sustains DNMT3A-R882-mutant clonal haematopoiesis.Nature 642:431-441 (2025).
  3. Damaskou A et al. Posttranscriptional depletion of ribosome biogenesis factors engenders therapeutic vulnerabilities in NPM1-mutant AML. https://doi.org/10.1182/blood.2024026113Blood146:1239-1252.(2025).
  4. Wen S et al. Comparative analysis of the Mexico City Prospective Study and the UK Biobank identifies ancestry-specific effects on clonal hematopoiesis.Nat Genet 57:572-582 (2025).
  5. Gu M et al. Multiparameter prediction of myeloid neoplasia risk.Nat Genet.1523-30 (2023).
  6. Cheloor Kovilakam S et al.Prevalence and significance of DDX41 gene variants in the general population.Blood (2023).
  7. Kar SP et al.Genome-wide analyses of 200,453 individuals yield new insights into the causes and consequences of clonal hematopoiesis.Nat Genet54, 1155-1166 (2022).
  8. Fabre MA et al.The longitudinal dynamics and natural history of clonal haematopoiesis.Nature 606, 335-342 (2022).
  9. Gozdecka M et al.UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.Nat Genet 50, 883-894 (2018).
  10. Abelson S et al.Prediction of acute myeloid leukaemia risk in healthy individuals.Nature 559, 400-404 (2018).
  11. Barbieri I et al.Promoter-bound METTL3 maintains myeloid leukaemia by m(6)A-dependent translation control.Nature 552, 126-131 (2017).
  12. Tzelepis K et al.A CRISPR Dropout Screen Identifies Genetic Vulnerabilities and Therapeutic Targets in Acute Myeloid Leukemia.Cell Rep 17, 1193-1205 (2016).
  13. McKerrell T et al.Leukemia-associated somatic mutations drive distinct patterns of age-related clonal hemopoiesis.Cell Rep 10, 1239-1245 (2015).
  14.  Vassiliou GS et al.Mutant nucleophosmin and cooperating pathways drive leukemia initiation and progression in mice.Nat Genet 43, 470-475 (2011).