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Cancer Prevention: targeting the bone microenvironment to prevent myeloma

Supervisors

Professor Claire Edwards and Dr Beatriz Gamez, Nuffield Department of Surgical Sciences

About this project

Multiple myeloma is an incurable cancer of plasma cells that is preceded by monoclonal gammopathy of undetermined significance (MGUS). While significant advances have been made in the treatment of myeloma, the mechanisms underlying MGUS progression are poorly understood. Aging and obesity are two of the major risk factors for myeloma, however a comprehensive understanding of the cellular and molecular mechanisms by which they drive myeloma development are needed. The Edwards lab is part of an international multidisciplinary team which aims to integrate biological, bioinformatic and health economic research to address this.

This project will study the interactions between tumour cells and cells of the bone microenvironment to investigate the roles of adiponectin/ceramide/sphingolipid signaling in myeloma progression. The project will employ a powerful combination of in vitro cellular and molecular biology, preclinical models of myeloma and primary samples from patients with MGUS and myeloma. Metabolomics and transcriptomics will interrogate the impact of aging and obesity on the myeloma-bone microenvironment. This project will provide a unique opportunity, working within the research fields of tumour biology and bone biology, and joining an international multidisciplinary team. State-of-the-art approaches will be used, including advanced cell culture systems, microfluidic devices, RNA-Seq, CRISPR/Cas9-mediated gene editing and metabolomics 

The Research Group

The student will be jointly supervised by Prof. Claire Edwards (Nuffield Dept. of Surgical Sciences (NDS)/Nuffield Dept. of Orthopaedics, Rheumatology and Musculoskeletal Sciences (NDORMS)) and Dr. Beatriz Gamez (NDS). They will be based within the Edwards group at the Botnar Institute for Musculoskeletal Sciences, currently comprised of three postdoctoral research associates, four DPhil students, one MSc by research student and two research assistants. For informal enquiries, please contact Claire Edwards claire.edwards@nds.ox.ac.uk or Beatriz Gamez beatriz.gamezmolina@nds.ox.ac.uk

Training

The Botnar Institute of Musculoskeletal Sciences supports research and education into the causes of musculoskeletal disease and their treatment. Lectures are available to provide a solid foundation in a broad range of subjects including musculoskeletal biology, epigenetics, translational immunology and data analysis. Students will also be required to attend regular seminars within the Department and those relevant in the wider University. Students will be expected to present data regularly in Departmental seminars, the Edwards’ lab group meetings and to attend external conferences to present their research globally. Students will have access to various courses run by the Medical Sciences Division Skills Training and other Departments. 

Relevant Publications 

1.         Gamez B, Edwards CM. Contributions of the Bone Microenvironment to Monoclonal Gammopathy of Undetermined Significance Pathogenesis. Current osteoporosis reports. 2018;16(6):635-41.

2.         Gamez B, Morris EV, Olechnowicz SWZ, Webb S, Edwards JR, Sowman A, et al. The antidiabetic drug metformin acts on the bone microenvironment to promote myeloma cell adhesion to preosteoblasts and increase myeloma tumour burden in vivo. Transl Oncol. 2022;15(1):101301.

3.         Gooding S, Olechnowicz SWZ, Morris EV, Armitage AE, Arezes J, Frost J, et al. Transcriptomic profiling of the myeloma bone-lining niche reveals BMP signalling inhibition to improve bone disease. Nature communications. 2019;10(1):4533.

4.         Lwin ST, Olechnowicz SW, Fowler JA, Edwards CM. Diet-induced obesity promotes a myeloma-like condition in vivo. Leukemia. 2015;29(2):507-10.

5.         Morris EV, Suchacki KJ, Hocking J, Cartwright R, Sowman A, Gamez B, et al. Myeloma Cells Down-Regulate Adiponectin in Bone Marrow Adipocytes Via TNF-Alpha. J Bone Miner Res. 2020;35(5):942-55.