Investigating the role and function of top scoring genes identified through a meta-analysis of CML LSC datasets, focusing on RXFP1
Supervisors
Prof Vignir Helgason, School of Cancer Sciences, University of Glasgow
Dr Kiron Roy, School of Cancer Sciences, University of Glasgow
Dr Samanta Mariani, School of Regeneration and Repair, University of Edinburgh
Summary
Chronic myeloid leukaemia (CML) is a myeloproliferative disease driven by a translocation between chromosomes 9 and 22 in a haematopoietic stem cell (HSC), resulting in the formation of a leukaemic stem cell (LSC). This translocation causes the formation of an aberrant chromosome known as the Philadelphia Chromosome, which contains the fusion oncogene breakpoint cluster region abelson murine leukaemia 1 (BCR::ABL1), a constitutively active tyrosine kinase. The presence and signalling of BCR::ABL1 is the single requirement for the development of CML, and so, targeting BCR::ABL1 using tyrosine kinase inhibitors (TKIs) is a paradigm for precision medicine and a highly effective method of stemming disease progression. However, administration of TKI is rarely curative, representing an unmet clinical need. From a meta-analysis of CML datasets, we identified numerous candidate genes which could represent new therapeutic targets, with the top scoring uncharacterised gene being RXFP1. We aim for a student to explore the effects of inhibiting RXFP1 and uncovering its novel mechanism of action in LSCs both in-vitro and in xenograft models, using a variety of bench and bioinformatic methods. Should perturbing RXFP1 signalling have no effect, other candidate genes can be investigated. In selecting this project, a student can expect to be trained in a wide array of laboratory and computational techniques, and to be part of an enthusiastic and outgoing team of leukaemia researchers.
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