Project title
(VIDA DTC) The role of type 2 diabetes, retinal vasculopathy and inflammation in post-stroke cognitive decline
About the project
VIDA (Vascular and Immune contributions to DementiA) is a new multi-institutional partnership between four world-leading research sites: the University of Manchester, University of Edinburgh, Imperial, and St George’s University of London. With projects focussing on the Vascular and Immune contributions to DementiA, VIDA PhD students will become the next generation of much-needed dementia researchers, contributing to breakthroughs in dementia diagnosis, treatment, and care.
VIDA students will embark upon a four-year fully-funded PhD project at one of the institutions above, with access to the state-of-the-art research facilities and interdisciplinary training available at all sites. Students at each site will come together as a cohort at several points during the programme, most importantly for an induction week at the beginning of the programme, followed by annual conferences, and residential workshop retreats. Students will also participate in engagement schemes with the Alzheimer’s Society and beyond, sharing the impact of their research in the community. The programme also benefits from built-in opportunities for placements with leading industrial partners, and bespoke training plans including schemes to develop teaching, mentoring, and grant writing skills.
Supervisory team
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Dr Zhang is a consultant in neurology and stroke medicine at St George’s University Hospitals, with special clinical interests in stroke and central nervous system inflammation. Dr Zhang is the stroke clinical research lead at St George’s. She is on the editorial board for Advanced Neurology.
She is the chief investigator in the UK for several international stroke clinical trials and is currently the principal investigator for multiple clinical trials involving stroke and multiple sclerosis. Dr Zhang has a longstanding interest in stroke related inflammation since her PhD at Pennsylvania State University, where she used db/db mice to study inflammation in diabetic ischemic brain damage. Dr Zhang teaches medical students at St George’s, and supervises MSc students.
Professor Craig Smith's research is focused on the translational theme of inflammation, immunity and infection in cerebrovascular disease and is inter-disciplinary in nature. Inflammation, infections and immune dysregulation influence both the risk and causation of stroke, and also have a significant impact on the outcome after a stroke. For example, pneumonia complicates at least 10% of strokes and has a devastating effect on clinical outcomes, increasing the chances of death 3 fold. Targeting inflammation, immune responses and infections in this setting therefore offers exciting therapeutic opportunities to modify stroke risk and improve outcomes for patients.
Craig is interested in how inflammation and immune responses are altered prior to, and after stroke, and how these responses (and infections) might contribute to worse outcome. His interests also cover how we can more accurately diagnose pneumonia after stroke, better predict which patients are at risk of developing it, and improve care processes/ develop interventions to reduce the occurence of pneumonia.
His research includes experimental studies of respiratory tract infection as a translational infection paradigm in pre-clinical stroke (Professor Stuart Allan, Dr Kieron South). It also includes wide-ranging clinical studies of inflammatory/immune mechanistic and prognostic biomarkers in stroke and infection; plus intervention studies to reduce harmful inflammation produced after stroke, and interventions to reduce the risk of pneumonia by targeting oral biofilm and oro-pharyngeal aspiration. More recently, his research has focused on the links between infection with COVID-19, thromboinflammation and stroke.
Dr Benjamin is a consultant neuroradiologist between St Georges University Hospitals and the Royal Marsden and has expertise across the fields of cerebrovascular disease, neurodegeneration and neuro-oncology, which puts him in a unique position to be able to carry out multidisciplinary research. He has a particular interest in stroke and small vessel disease imaging and was the first in the UK to evaluate and optimise 7T MRI for use in small vessel disease. He is the named neuroradiologist on a number of research studies and clinical trials at St Georges, the Royal Marsden and Cambridge University.
Professor Alicja Rudnicka is a Professor in Statistical Epidemiology in the Population Health Research Institute. Professor Rudnicka has been involved in a wide spectrum of epidemiological enquiry including large-scale population based studies and the application of artificial intelligence (AI) technology for analyzing retinal images for risk prediction and disease detection. She is involved in evaluating AI technology to analyse retinal images to detect sight-threatening diabetic eye disease patients with diabetes attending for annual screening for eye disease. Within the Population Health Research Institute she collaborates with colleagues on other areas of public health importance including, accuracy of body composition measurement in children in different ethnic groups, interventions to improve sleep in children and adolescents as well as collaborating with colleagues within St George's University Hospital Trust on a wide range of clinical outcomes.
Project description
Most dementia has a vascular component. The prevalence of dementia is brought forward by 25 years in those with stroke compared with those without. Type II diabetes is an independent risk factor for stroke, especially ischemic stroke. Diabetes is associated with an increased risk of post-stroke dementia, independent of the stroke severity.
Pre-clinical and clinical data have shown that inflammation plays a key role in both the acute and chronic phases of ischemic stroke, including the development of dementia. In patients with type II diabetes, chronic hyperglycaemia causes chronic low-grade inflammation. This disrupts the balance of pro- and anti-inflammatory responses, resulting in more severe acute ischemic brain damage. Inflammation after a stroke can last for months or even years, resulting in neurodegeneration. Diabetic retinopathy is an early diabetes complication, driven by inflammation. Individuals with diabetic retinopathy have 34 % higher risk of incident dementia.
Despite promising results of anti-inflammation treatments in preclinical studies, studies of functional clinical outcome after stroke have been inconclusive. There are few studies on the role of inflammation in post-stroke cognitive dysfunction/dementia, and very few in high-risk diabetic stroke patients.
The aims of this PhD project are i) to examine pro- and anti-inflammation blood biomarkers during the course of clinical ischaemic stroke in patients with or without type II diabetes, ii) to explore the temporal patterns of inflammation in acute ischemic stroke and post-stroke cognitive decline, iii) to correlate these inflammation markers with clinical imaging findings and retinopathy biomarkers. Focusing on diabetic patients, this study will provide evidence of type II diabetes related inflammation in post stroke cognitive decline, identify strategies for early screening and intervention to prevent dementia.
St George’s University Hospital is a major comprehensive stroke centre in southwest London with high ethnic diversity of patient population, especially Asian patients of high prevalence in type II diabetes. St George’s University Hospital has an established and experience clinical stroke research team. University of Manchester has an international reputation in vascular inflammation and translational neuroscience. The studentship will link these two expert centres and provide training in setting up clinical study, lab skills, vascular and neuroimaging, cognitive assessment, data-analytics, statistics, with a potential of long-term clinical / academic development.
Skills acquisition
The studentship will link these two expert centres and provide training in setting up clinical study, lab skills, vascular and neuroimaging, cognitive assessment, data-analytics, statistics, with a potential of long-term clinical / academic development.
The programme also benefits from built in opportunities for placements with leading industrial partners, and bespoke training plans including schemes to develop teaching, mentoring, and grant writing skills.
Entry requirements
Applicants are expected to hold (or about to obtain) a minimum upper second class undergraduate honours degree (or equivalent) in a biomedical science or medicine. Experience in neuroscience and/or immunology is desirable.
Funding
This four-year studentship is open to UK and international students and provides funding to cover stipend (maintenance allowance at UKRI rate, set at £22,500 per year, paid in monthly instalments) and home tuition fees.
No international fees will be waived; students will be responsible for additional fees. However, St George's is prepared to consider individual cases if requested and a justification for funds can be made.
Funding is also provided for research expenses, career development, and student travel/conference attendance.
Application process
The following documents should be submitted to stgeorgesphd@sgul.ac.uk no later than Friday 20 December 2024, 23.59 GMT:
- Personal statement about your reasons for applying for this studentship (maximum one page)
- Curriculum Vitae (maximum two pages)
- Two references. Applicants should arrange for two relevant referees to submit letters of reference via email before the deadline.
Interested candidates must first make contact with the Primary Supervisor Dr Liqun Zhang prior to submitting a formal application, to discuss their interest and suitability for the project. Informal enquiries can be sent via email to liqun.zhang@stgeorges.nhs.uk
Interviews will likely take place in March 2025. Candidates will be asked to give an eight-minute presentation on a previous/on-going research project that showcases skills and knowledge, followed by questions on the presentation and the application.