Multiple Myeloma (MM) is a haematological cancer caused by abnormal plasma cell expansion in the bone marrow. MM is preceded by an earlier clinically stable stage termed monoclonal gammopathy of undetermined significance (MGUS). Approximately 1% of people with MGUS will develop MM each year yet there is no clinical intervention to prevent this transformation. Mouse modelling of MGUS suggests that clinical dormancy may be regulated in part by growth controls extrinsic to the tumour cells. Thus, interactions with cells and factors in the bone marrow are key regulators of malignant transformation.
Gut microbes communicate with the host through microbiota-derived metabolites such as the short-chain fatty acids (SCFAs); various SCFA have been identified as important anti-cancer agents in different cancers. Alterations in the gut microbiome have been documented in MM patients with a reduced number of SCFA-producing bacteria. However, a possible link between SCFA and malignant transformation from MGUS to MM and whether SCFA supplementation can prevent this remains to be explored.
This project will investigate how gut-derived metabolites influence MM progression using a combination of in vivo mouse models of MGUS and MM, as well as ex vivo analysis of patient samples. Analysis of cellular responses to SCFA will be assessed at the cellular level (FACS, mass cytometry) and at the molecular level (qPCR, RNASeq). This work will generate pre-clinical data for future clinical translation for those living with MGUS.
The project would be suitable for candidates interested in prevention and therapy of haematological malignancies, gut dysbiosis and bioinformatics. At Norwich Medical School, the student will receive training in in vivo disease models, in vitro dissection of disease mechanisms, and computational modelling as well as training in scientific writing, presentation, data management, statistical analysis and will be encouraged to attend and present at national and international conferences.
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