Psoriatic Arthritis, comorbidity and treatment burden: Personalised risk stratification based on risk of adverse clinical outcomes
Supervisors
Barbara Nicholl, School of Health & Wellbeing, University of Glasgow
Bhautesh Jani, School of Health & Wellbeing, University of Glasgow
Stefan Siebert, School of Infection and Immunity, University of Glasgow
Frances Mair, School of Infection and Immunity, University of Glasgow
Summary
A large proportion of people with psoriatic arthritis experience other long-term health conditions that are likely to also have an impact on their health outcomes. The presence of two or more long-term health conditions (known as multimorbidity) among individuals with psoriatic arthritis means that they can have complicated healthcare needs which result in increased visits to the doctor and unplanned stays in hospital. Treatment burden is the workload of healthcare experienced by those with long-term conditions and the impact that this has on wellbeing. The impact of multimorbidity and treatment burden on patients with psoriatic arthritis is unstudied.
The main aim of this study is to use routinely collected data and prospective research cohorts of people with psoriatic arthritis to understand the implications of presence of other long-term conditions and measure treatment burden in psoriatic arthritis. We also want to find out how multimorbidity and treatment burden is associated with disease-specific and adverse clinical outcomes in psoriatic arthritis.
This work has the potential to identify those patients with psoriatic arthritis who are at a higher risk of poor health due to the presence of additional long-term conditions and treatment burden. It will help inform policy and treatment decisions to improve care for patients with psoriatic arthritis.
Investigating the multifaceted effects of DNA damage response inhibitors on the glioblastoma microenvironment.
Supervisors
Anthony Chalmers, School of Cancer Sciences, University of Glasgow
Nigel Jamieson, School of Cancer Sciences, University of Glasgow
Gerry Thompson, Centre for Clinical Brain Sciences, University of Edinburgh
Summary
Glioblastomas (GBM) are incurable, aggressive brain tumours that are resistant to radiotherapy and chemotherapy and exert immunosuppressive effects that contribute to poor outcomes. Microglia are brain-resident immune cells that promote glioblastoma growth and suppress antitumour immune responses. AstraZeneca has developed a brain-penetrant ATM inhibitor (AZD1390) that is an extremely potent radiosensitizer currently being tested in clinical trials in GBM patients. The Chalmers lab has recently shown that the combination of AZD1390 and radiotherapy causes prolonged depletion of microglia in the mouse brain – raising the possibility that it might enhance the therapeutic effects of radiotherapy in GBM by overcoming tumour resistance and unlock an anti-tumour immune response. Interactions between GBM and the tumour microenvionment (including microglia and other immune cells) are extremely complex and heterogenous, however, and cannot be studied in isolation.
The proposed project will utilize existing immunocompetent intracranial mouse models of GBM and freshly derived patient GBM material cultured as brain slices to interrogate the effects of radiotherapy +/- AZD1390 on the tumour microenvironment, with particular focus on microglia and immune responses. World leading spatial transcriptomic and proteomic techniques in the Jamieson laboratory will be applied with the aim of understanding the mechanisms underpinning therapeutic efficacy and resistance, and identifying biomarkers that might predict which patients would benefit from the AZD1390-radiotherapy combination. A multi-disciplinary, translational supervisory team will comprise Anthony Chalmers (Chair of Clinical Oncology, University of Glasgow), Nigel Jamieson (Professor of Surgery, University of Glasgow), Paul Brennan (Reader in Neurosurgery, University of Edinburgh) and Gerry Thompson (Senior Lecturer in Neuroradiology, University of Edinburgh).