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Psaila Group: The tumour microenvironment in blood cancers

  • MRC MHU

Adjunct to the Oxford Ludwig Institute for Cancer Research

We focus on four key areas: (1) Dissecting how blood cancers create 'self-reinforcing' niches that promote clonal expansion and protect malignant clones from immunotherapies; (2) Development and application of human bone marrow organoids to study normal and malignant haematopoiesis and validate targets in a relevant tissue microenvironment; (3) Developing novel strategies to selectively target cancer stem cells and pathological megakaryocytes in myelofibrosis, a severe bone marrow malignancy; (4) Understanding our recent discovery that platelets contain a repertoire of DNA fragments sequestered from cell free DNA, and confirming clinical utility for cancer detection and for pre-natal diagnosis.

The malignant bone marrow niche

Our key areas of research are:

Megakaryocytes as 'stealth' players in blood cancer pathobiology

Megakaryocytes are bone marrow cells that produce blood platelets and also release and store proteins that regulate blood cell development and the bone marrow microenvironment. We apply a range of approaches to dissect the molecular and cellular pathways by which megakaryocytes arise from blood stem cells. This is important as in certain blood cancers, such as myeloproliferative neoplasms, megakaryocytes develop abnormally and contribute to key disease features, including the development of harmful scarring (fibrosis) that destroys the bone marrow. Megakaryocytes also undergo an unusual form of the cell cycle called endomitosis, in which they continue to duplicate their genome without completing cell division. Understanding how megakaryocytes tolerate whole genome duplication, and the implications for their genome integrity, is broadly relevant across cancer biology. 

Mechanisms of pathological bone marrow fibrosis

Interrogating how abnormal cross-talk between megakaryocytes, stem cells and the bone marrow stroma triggers fibrosis development in a subset of patients with myeloid blood cancers, and how this may be prevented. 

Discovery and validation of new therapies for blood cancers using human bone marrow organoids

Validation of novel therapies requires testing against patient cells in a relevant human tissue environment. This has been a longstanding challenge in the field. To tackle this, we developed an implement a new human bone marrow organoids platform which recapitulates key cellular, molecular and architectural features of native human bone marrow ex vivo. 

Role of platelets in early detection of cancer

We are also interested in the role of platelets in cancer, in particular in how they may serve as diagnostic biomarkers for early cancer detection.

 

Our research is focused on discovery of targetable drivers of cancer biology. Several projects are at the interface between discovery science and clinical translation. Our overarching goal is to identify disease-modifying therapies that improve outcomes for patients with cancer. 

 

https://www.psailalab.com/

Our team

Selected publications