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Targeting cancer stem cells in acute myeloid leukaemia (AML)


Project Description

Applications are invited for a Clinical Fellowship at the Barts Cancer Institute (Queen Mary University of London) to join a dynamic research group led by Professor Kamil R Kranc. We seek motivated clinicians (haematology, internal medicine and oncology trainees) who are passionate about cancer research and have an ambition to pursue a career as an academic clinician.

This fellowship will be based in the Centre for Haemato-Oncology, a centre of excellence in state-of-the-art research and clinical translation, which brings together internationally-recognised basic scientists with top clinical academics. Working closely together with the Haemato-oncology department at the St Bartholomew’s Hospital Cancer Centre we are uniquely placed to implement our findings in clinical practice. The Centre is embedded in Barts and The London School of Medicine and Dentistry, one of the UK’s top medical schools, thus offering excellent opportunities for multidisciplinary collaborations and career progression.

The central aim of this fellowship is to identify and validate novel therapeutic targets for eliminating cancer stem cells in AML. Recent evidence revealed the key significance of RNA modifications in normal haematopoiesis and leukaemic transformation. The outcome of RNA modifications is executed by the reader proteins which bind modified mRNA to mediate transcript translation, splicing or degradation. We have revealed that one of these readers is overexpressed in a broad spectrum of human AML and is required for disease initiation, as well as propagation in mouse models of AML (Paris et at, Cell Stem Cell, 2019). The fellow will identify other similar reader proteins and determine the therapeutic value of targeting them to eliminate cancer stem cells in AML. Given that AML is a paradigm for many other cancer stem cell-driven tumours, this fellowship will be highly relevant not only to haematology trainees, but also to oncology trainees.

The fellow will obtain multidisciplinary laboratory training in state-of-the-art approaches including, but not limited to: normal and malignant stem cell biology, advanced mouse genetics, mouse models of human leukaemia, advanced flow cytometry, molecular biology, experimental pharmacology, and aspects of drug discovery.

This project will be supervised by Professor Kamil Kranc (Barts Cancer Institute) and co-supervised by Professor Donal O’Carroll (University of Edinburgh). Informal enquiries are encouraged and should be sent to Professor Kamil R Kranc ().
Selected recent publications from the supervisory team are listed below.

Funding Notes

The Trustees of The Medical College of Saint Bartholomew’s Hospital Trust (MCSBHT) have offered funding for three research studentships (two in medicine and one in dentistry), for clinically qualified candidates within the Barts and The London School of Medicine and Dentistry to commence in October 2020, leading to a PhD degree.

Funded studentships will be open to potential students with a clinical qualification and GMC / GDC registration at any career stage below consultant. They will be funded for three years at current, MRC rates. Studentships will include PhD fees (at home/EU levels) and up to £6000 pa for consumables. Further consumables / funding for travel may be available on application.

References

Paris, J. et al. Targeting the RNA m(6)A Reader YTHDF2 Selectively Compromises Cancer Stem Cells in Acute Myeloid Leukemia. Cell Stem Cell 25, 137-148, (2019).
Baumeister, J. et al. Hypoxia-inducible factor 1 (HIF-1) is a new therapeutic target in JAK2V617F-positive myeloproliferative neoplasms. Leukemia, doi:10.1038/s41375-019-0629-z (2019).
Morgan, M. et al. mRNA 3' uridylation and poly(A) tail length sculpt the mammalian maternal transcriptome. Nature 548, 347-351 (2017).
Ivanova, I. et al. The RNA m(6)A Reader YTHDF2 Is Essential for the Post-transcriptional Regulation of the Maternal Transcriptome and Oocyte Competence. Mol Cell 67, 1059-1067 (2017).
Guitart, A. V. et al. Fumarate hydratase is a critical metabolic regulator of hematopoietic stem cell functions. J Exp Med 214, 719-735 (2017).
Vukovic, M. et al. Hif-1alpha and Hif-2alpha synergize to suppress AML development but are dispensable for disease maintenance. J Exp Med 212, 2223-2234 (2015).

How good is research at Queen Mary University of London in Clinical Medicine?

FTE Category A staff submitted: 144.11

Research output data provided by the Research Excellence Framework (REF)

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