Leukaemic & preleukaemic haemopoietic stem cells

About the project

About the Project Group Leader: Professor George Vassiliou ( Vassiliou Group ) Keywords: Clonal haematopoiesis, telomeres, leukaemia prevention Research Summary 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. To Apply: We encourage prospective PhD students to reach out directly to Professor Vassiliou, gsv20@cam.ac.uk to discuss potential projects and supervision. Applicants must secure the support of a Supervisor within a laboratory before submitting an application . Please contact the project Supervisor(s) to discuss potential supervision, proposed research project and funding options, which should then be used to write your formal application. Applications will be submitted to the ' PhD in Stem Cell Biology ' and full course details can be found at https://www.postgraduate.study.cam.ac.uk/courses/directory/blscpdscp

Research areas