Harsh Bhatt was awarded a Brain Research UK PhD studentship in 2022 to enable him to pursue research into glioblastoma, one of the deadliest human cancers.
As an academic neurosurgery trainee, Harsh has treated many patients with glioblastoma and is passionate about improving understanding of their disease and helping improve treatments. This PhD studentship enabled him to take time out from his neurosurgical training to pursue this aim.
Harsh said: “The Brain Research UK studentship has been instrumental in supporting me through my PhD, helping me learn invaluable new skills as well as supporting my continued career development as a clinical-academic trainee…. Brain Research UK’s support has also enabled me to gain experience of presenting our work at national and international conferences, seek inputs from leading experts, and develop a growing collaborative network of clinicians and scientists interested in translational brain tumour biology. I am deeply thankful for the experience I have gained.”
Glioblastoma is the most common primary brain cancer in adults, with around 2,500 cases diagnosed every year in the UK.
Glioblastoma is a grade 4 tumour, meaning that it grows and spreads quickly. It infiltrates the brain, wrapping finger-like tentacles around vital brain structures, making complete surgical removal impossible.
The current treatment strategy includes surgery to remove as much tumour as possible, followed by radiotherapy and chemotherapy to destroy remaining tumour. This prolongs survival but is not curative. Only a quarter of patients survive more than a year from diagnosis.
The need for new treatments is urgent.
Read more: About brain tumours
Harsh’s research focuses on telomeres, sections of DNA that cap and protect the ends of our chromosomes. Telomeres shorten each time a cell divides, including during the formation of cancer cells – a process that involves rapid cell division. This shortening can cause chromosomes to fuse together and is a key step in the formation and growth of many cancers.
During his PhD, Harsh worked with Professor Duncan Baird, whose lab has pioneered research into telomere dysfunction and its role in cancer development. Research from this lab has already shown that telomere length and the presence of fusions can help predict survival of patients with leukaemia and breast cancer.
For this project, Harsh and his colleagues studied 146 patients with glioblastoma (GBM) and analysed their tumours for precise telomere length measurements. This showed that knowing a tumour’s telomere length can add powerful prognostic value to current best-used tests (biomarkers) for predicting patient survival. The team also learnt that there might be subgroups of patients with GBM in whom shorter telomeres predict much better survival, compared to other subgroups for whom shorter telomeres were much more detrimental. This difference might depend on the tumour’s abilities to faithfully repair damaged DNA after, for example, the patient has had radiation and chemotherapy treatments.
The team also found that in patients with GBM, telomeres are generally much shorter when compared to those in a normal brain, and that chromosomal fusions and rearrangements of genetic material seem widespread. These fusions showed signs of relying on specific repair mechanisms for damaged DNA, which may make such tumours suitable for particular targeted treatments.
In addition, the team identified telomere fusions within lower-grade gliomas (less aggressive tumours which also originated in the brain), and that the nature of these fusions relied more on the mechanism tumours were using to maintain telomere length, rather than their pathological subtype or World Health Organisation severity grade.
Finally, in a handful of patients, the team were able to compare the same tumour at first surgery and when it grew back after treatment, to assess differences in their telomere length and fusions over time and following treatment. The team learnt that telomere length may not remain the same in a tumour over time, and that a less diverse spectrum of chromosomal fusion types is seen when the cancer came back.
Finding out the precise high-resolution telomere length in the brain tumours of patients with GBM, whether this changes over time and after treatment, and whether it can help better predict survival or identify subgroups for prioritisation towards alternate novel therapies, are new and important learnings to help improve our understanding and treatment of this deadly cancer. Knowing patients’ tumour telomere lengths and underlying faulty DNA repair mechanisms could also help clinicians predict who will benefit from certain targeted treatments, and reduce harm in other treatments.
The team now hope to validate some of their findings in external cohorts, and that these learnings can then be used in the design of future clinical trials.
As well as advancing knowledge about glioblastoma, this studentship supported the career development of a neurosurgeon who is committed to pursuing an academic career focused on neuro-oncology. There are few neurosurgeons in the UK with this kind of training, and the need for more clinical academics is acute.
Bhatt, H., Norris, K., Cleal, K., Hodgson, M., Herbert, C., Gray, W., Kurian, K., & Baird, D. Telomere dysfunction and fusions in glioblastoma - defining prognosis and genome instability. Neuro-Oncology, Volume 27, Issue Supplement_5, November 2025, Page v152. https://doi.org/10.1093/neuonc/noaf201.0600
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