- Dr Romal Stewart
Cancer is the single biggest clinical problem facing the world and will account for half of all global deaths by 2030. Even though there have been significant advances in immunotherapy, we are still unable to cure most cancers. New therapeutic targets, individualised to patient needs, must be identified and validated in order to improve cancer outcomes.
Brain cancer causes more deaths in people under the age of 40 than any other cancer and more deaths in children than any other disease. The survival rates of brain cancer are low and have not changed much in the 30 years. Genomic instability is a hallmark of cancer. To prevent cancer, cells possess a complex network of signalling pathways called the DNA damage response, which is involved in the detection, signalling and subsequent repair of DNA. Failure of the DNA damage response leads to cancer and tumorigenesis.
A family of copper metabolism gene MURR1 domain (COMMD) proteins, have shown promise as potential therapeutic targets in several cancers. COMMD4 is a novel DNA repair protein, which functions in the DNA damage response. COMMD4 functions with the histone H2A-H2B dimer for the timely repair of DNA breaks.
The overall aim of this research project is to determine whether depletion of COMMD4 specifically kills brain cancer cells. The specific aims and objectives of this project are:
- To investigate the therapeutic potential of COMMD4 in brain cancers in vitro.
- Validate COMMD4 as a diagnostic marker in brain cancers.
- Suraweera A, Gandhi N.S, Beard S, Burgess J.T, Croft L.V, Bolderson E, Naqi A, Ashton N.W, Adams M.N, Savage K, Zhang S.D, O’Byrne K.J, Richard D.J. COMMD4 functions with the histone H2A-H2B dimer for the timely repair of DNA double-strand breaks. Communications Biology 2021; 4(1): 1-11.
- Suraweera A, Duff A, Adams M.N, Jekimovs C, Duijf P, Liu C, McTaggart M, Beard S, O’Byrne K.J, Richard D.J. Defining COMMD4 as an anti-cancer therapeutic target and prognostic factor in non-small cell lung cancer. British Journal of Cancer 2020; 123:591-603.
Aims 1 and 2 will involve:
- cell culture
- transfection of mammalian cells
- siRNA depletion
- western blotting
- clonogenic cell viability assays
- cell proliferation assays.
This project presents a unique opportunity to determine whether a novel DNA repair protein is a good therapeutic target and biomarker in brain cancers.
Contact the supervisor for more information.