Targeting the leukaemic niche: does macrophage crosstalk sustain TP53-mutant acute erythroid leukaemia

Closing date: 15/03/2027

MB-PhD Studentship: Targeting the leukaemic niche: does macrophage crosstalk sustain TP53-mutant acute erythroid leukaemia

Lead Supervisors: Dr Justin Loke
Lead Supervisors: Professor Tim Somervaille, Dr Simona Valetta, Dr Dan Wiseman

Applications Deadline: Monday 15th March 2027
Interviews: Week commencing 3rd May 2027
Start date: September 2027

Project Keywords: Leukaemia, tumour microenvironment, functional genomics 
Research Opportunity: MB-PhD Studentship

Project Outline

Blood cancers arise from mutations in genes controlling normal stem cell development, but cancer cells do not grow in isolation — they are supported by the normal cells that surround them. Acute myeloid leukaemia (AML) carrying mutations in the TP53 gene has a particularly poor prognosis, with most patients surviving under six months and no targeted treatment available. New approaches are urgently needed. 

In healthy bone marrow, specialised cells nurse developing red blood cells. We have developed a new transgenic mouse expressing a CRISPR enzyme that allows several genes to be edited simultaneously in blood stem cells. Using this, we have created a model of TP53-mutant acute erythroid leukaemia in which the bone marrow becomes heavily infiltrated with inflammatory cells, and in which leukaemia cells will not survive outside the body — suggesting they depend on signals from neighbouring cells.  

This project asks whether these neighbouring cells keep TP53-mutant leukaemia alive, and whether removing that support can kill it. You will use CRISPR editing to delete candidate adhesion molecules and test whether they are required for disease in mice; deplete neighbouring cells directly and ask whether this improves response to venetoclax and azacitidine; and map normal and leukaemia cells in patient bone marrow biopsies using multiplex imaging. 

You will benefit from training across molecular biology, in vivo modelling, flow cytometry, multiplex tissue imaging and bioinformatics, alongside broad exposure to the clinical activity of The Christie Haematology Department. You will become expert in the biology of high-risk myeloid disease, and develop the independence to pursue your own lines of enquiry. 

Applications for this project are now open. Please complete your application on The University of Manchester Postgraduate Application Portal.

About Dr Justin Loke (project Lead Supervisor)

Justin Loke is a clinician scientist and Institute Fellow at the CRUK Manchester Institute, where he is establishing his new group Myeloid Cancer Biology. He is a Consultant Haematologist at the Christie NHS Foundation Trust. His specialist interest is in the myeloid blood cancers including acute myeloid leukaemia (AML).

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