Role of macrophage heparan sulfate proteoglycans in multiple myeloma (TROEBERGL_U25BIGC)
Key Details
- Application deadline
- 31 March 2025 (midnight UK time)
- Location
- UEA
- Funding type
- Directly Funded Project (UK/Home Students Only)
- Start date
- 1 October 2025
- Mode of study
- Full-time
- Programme type
- PhD
Project description
Primary supervisor - Dr Linda Troeberg
This 4-year PhD project, funded by Big C Cancer Charity and UEA Faculty of Medicine and Health Sciences, represents an exciting opportunity to develop and conduct cutting-edge research on cancer immunology.
Multiple myeloma (MM) is a malignancy of plasma cells, the cell type that makes antibodies. MM remains incurable, with under a third of UK patients surviving their disease for more than 10 years. There is thus an unmet clinical need for new therapies that can stop MM progressing or eradicate residual disease. This project will investigate how MM cells communicate with tumour-associated macrophages (TAMs), which maintain an immunosuppressive environment that supports MM proliferation, survival, and drug resistance. Understanding how TAMs receive and interpret signals from tumour cells could help us develop better treatments for MM and other cancers.
Our work so far has shown that macrophages regulate their expression of heparan sulfate proteoglycans (HSPGs) in response to cues that MM cells produce. We think this enables the macrophages to support tumour progression by altering how they respond to environmental cues such as cytokines and growth factors. To test this hypothesis, the PhD student will investigate how knockdown of candidate HSPG genes impacts the phenotype of macrophages in vitro, and validate their findings using clinical MM samples. To do this, they will receive training in immunology-focused cell and molecular biology techniques, including qPCR, immunoblotting, ELISA, flow cytometry, and immunohistochemistry.
The project will be carried out under the supervision of Dr Linda Troeberg and Prof Stuart Rushworth at Norwich Medical School. We have successfully supervised 15 PhD students, who have gone on to positions in post-doctoral research and industry. Our groups are supportive and collaborative, with weekly lab meetings and a biweekly journal club. We encourage presentation at local, national and international scientific meetings. Training will provide the opportunity to develop advanced research skills as well as broader transferable skills such as project management and scientific communication.
Entry requirements
The minimum entry requirement is 2:1 in Biological Sciences or equivalent.
Funding
This is a fully funded studentship which covers tuition fees, an annual maintenance stipend (starting at £20,006 in Year 1), and £1,000 per annum to support your research training.
References
i) The extracellular heparan sulfatase SULF2 limits myeloid IFNβ signaling and Th17 responses in inflammatory arthritis. Swart M, Redpath A, Ogbechi J, Cardenas R, Topping L, Compeer EB, Goddard M, Chanalaris A, Williams R, Brewer DS, Smart N, Monaco C, Troeberg L. (2024). Cellular and Molecular Life Sciences 81(1):350.
ii) Plasma cell derived mtDAMPs activate macrophage STING pathway which promotes myeloma progression. Jibril A, Hellmich C, Wojtowicz E, Hampton K, Maynard RS, De Silva R, Fowler-Shorten DJ, Mistry JJ, Moore JA, Bowles KM, Rushworth SA. (2023). Blood, 141(25):3065-3077
iii) LC3-associated phagocytosis in bone marrow macrophages suppresses acute myeloid leukemia progression through STING activation. Moore JA, Mistry JJ, Hellmich C, Horton RH, Wojtowicz EE, Jibril A, Jefferson M, Wileman T, Beraza N, Bowles KM, Rushworth SA. (2022). Journal of Clinical Investigation, 132(5), e153157
iv) Heparan sulfate as a regulator of inflammation and immunity. Collins LE, Troeberg L. (2019). Journal of Leukocyte Biology. https://doi.org/10.1002/JLB.3RU0618-246R
v) Perlecan (HSPG2) promotes structural, contractile, and metabolic development of human cardiomyocytes. Johnson BB, Cosson MV, Tsansizi LI, Holmes TL, Gilmore T, Hampton K, Song OR, Vo NTN, Nasir A, Chabronova A, Denning C, Peffers MJ, Merry CLR, Whitelock J, Troeberg L, Rushworth SA, Bernardo AS, Smith JGW. (2024). Cell Reports, 43(1):113668.