PhD projects available through TRAM
Breach of self tolerance is the key point in the development of autoimmunity. Our research has focussed on applying state of the art intravital microscopy to analyse the cellular and molecular interactions that underpin this important process. These have led to mechanistic studies identifying key cells and molecules involved and have informed translational studies.
The interaction between naïve T lymphocytes (T cells) and Dendritic Cells (DC), called the immune synapse, underpins the decision by the immune system to switch ‘on’ or ‘off’. In autoimmune diseases such as rheumatoid arthritis, the immune system makes the wrong decision to switch on, when it should be switching off. Compounds that can re-educate the immune system to make the right decision therefore have potential to treat disease. We have pioneered the use of advanced microscopy techniques to analyse the immune synapse. This has allowed us to screen thousands of chemicals, to identify synapse disruptors, that can perform immune re-education and may therefore have potential in treatment of autoimmune disease. We are currently working with Prof Carl Goodyear to characterise and understand the effects of synapse disruptors in treatment-resistant rheumatoid arthritis.
The interaction between naïve T lymphocytes (T cells) and Dendritic Cells (DC), called the immune synapse, underpins the decision by the immune system to switch ‘on’ or ‘off’. In autoimmune diseases such as rheumatoid arthritis, the immune system makes the wrong decision to switch on, when it should be switching off. Compounds that can re-educate the immune system to make the right decision therefore have potential to treat disease. We have pioneered the use of advanced microscopy techniques to analyse the immune synapse. This has allowed us to screen thousands of chemicals, to identify synapse disruptors, that can perform immune re-education and may therefore have potential in treatment of autoimmune disease. We are currently working with Prof Carl Goodyear to characterise and understand the effects of synapse disruptors in treatment-resistant rheumatoid arthritis.
Exemplar project, supervisors Jim Brewer and Carl Goodyear:
- Identify targets of lead aptamers. We will use pull down assays to selectively isolate aptamer binding partners from target cell homogenates, followed by identification using mass spectrometry.
- Understand the mechanism of action of lead aptamers. This will involve RNA sequencing of treated dendritic cells to identify pathways modulated by aptamer exposure.
- Assess in vivo activity. Mouse models of arthritis will be used to determine whether the aptamers can resolve inflammation.
- Evaluate functionality in arthritis. Using T cells and DCs isolated from the peripheral blood of patients with arthritis, we will analyse how the aptamers influence their interactions compared with existing drug treatments.
My research programmes are inspired by my rheumatology practice where I am drawn to areas of considerable need such as systemic vasculitis and chronic pain in people with inflammatory rheumatic diseases. Within my clinical studies, I integrate cutting edge ex-vivo immunological approaches alongside the latest in-vivo imaging platforms (7T MRI and Full Body PET) to decipher mechanisms and develop novel prognostic biomarkers.
Exemplar project titles:
- Could there be a role for B cell depletion in the management of large vessel vasculitis?
- Pioneering Full Body PET to dynamically map the immune system in patients with inflammatory arthritis
Professor Gwo-Tzer Ho
Professor of Gastroenterology | The Gut Translational Research Group
Gwo-Tzer.Ho@glasgow.ac.uk
Professor of Gastroenterology | The Gut Translational Research Group
Gwo-Tzer.Ho@glasgow.ac.uk
I am a clinician-scientist with a deep interest in Inflammatory Bowel Disease, Crohn’s disease and Ulcerative colitis. These are immune-mediated conditions that affect 10 million individuals world wide. In IBD, inflammation variably affects joints, gut, skin and eye, yet the mechanisms determining why particular tissues become involved, and why inflammation persists in some sites but not others, remain poorly understood. Up to a 1/3 of IBD patients, also have joint inflammation. As a translational immunology group, we aim to understand the immune-mechanisms that underpin these key clinical observations in our patients.
Exemplar project titles:
- Defining the homeostatic circuits that underpin the tissue states that determine inflammation in gut and joints
- Characterising the evolution of inflammation in joints and inflammation following immune-therapy in IBD
My research focuses on identifying and developing new therapeutic targets for autoimmune rheumatic and inflammatory diseases. I am particularly interested in studying changes in the synovial tissue to develop novel therapeutics to target stromal cells (for which none currently exist). This has involved me investigating how stromal cells change in response to different therapies (samples from the BEACON cohort: University of Birmingham) and how they change in JIA as part of the MAPJAG study. I have also led on projects to study the molecular changes in stromal cells using a range of functional approaches to investigate how these cells drive inflammatory diseases. Overall, I am keen to integrate data science with experimental immunology to maximise translational output. My current work now focuses on understanding age related changes in synovial tissue that shapes inflammatory arthritis to identify more specific targets to stromal cells.
Exemplar project titles:
- Why IMIDs fail to resolve: age dependent breakdown of tissue homeostasis in inflammatory arthritis
- Ageing-associated determinants of response and resistance in inflammatory arthritis
As a paediatric rheumatologist, I am motivated by improving the lives of children and young people who live with life-changing inflammatory conditions such as Childhood Lupus and Juvenile Idiopathic Arthritis. My research focuses on understanding these diseases better, finding ways to diagnose and treat them earlier, and improving long term outcomes.
I lead the TARGET LUPUS programme, which brings together international experts to develop better ways of treating childhood onset lupus. This includes the world’s largest study of young people with lupus, cSLE T2T Global, helping us understand outcomes and care across different countries. I also lead the NEPHROTARGET study, which looks at whether urine biomarkers can help guide treatment decisions.
I’m the paediatric lead for the national NIHR FIRST trial, which is testing whether using Rituximab earlier can improve outcomes in both children and adults with lupus. Alongside my lupus research, I also lead a functional MRI study running at four sites across the UK exploring how the brain processes pain in young people with arthritis.
I lead the TARGET LUPUS programme, which brings together international experts to develop better ways of treating childhood onset lupus. This includes the world’s largest study of young people with lupus, cSLE T2T Global, helping us understand outcomes and care across different countries. I also lead the NEPHROTARGET study, which looks at whether urine biomarkers can help guide treatment decisions.
I’m the paediatric lead for the national NIHR FIRST trial, which is testing whether using Rituximab earlier can improve outcomes in both children and adults with lupus. Alongside my lupus research, I also lead a functional MRI study running at four sites across the UK exploring how the brain processes pain in young people with arthritis.
Exemplar project titles:
- Predicting poor outcomes in Rheumatic Diseases affecting children and adults using real world data
- Using natural language processing (NLP) to improve diagnosis, phenotyping and long-term outcome studies in rheumatology
- Development and testing of a digital tool to support treat to target (T2T) in Childhood Lupus
- Understanding obesity across the life-course in Paediatric Rheumatic Diseases: prevalence, inequalities and clinical impact
- Neuroimmune signatures of pain in paediatric rheumatic diseases
I am a clinical academic working at the interface of rheumatology, neuroscience, and immunology. In my clinical practice, I work primarily with people living with inflammatory arthritis, particularly psoriatic arthritis, where ongoing pain remains a major unmet need. This drives my research focus on understanding how the brain and immune system interact to sustain pain in the context of chronic inflammation. I currently lead a clinical mechanistic study exploring how non-invasive brain stimulation modulates pain and immune pathways in psoriatic arthritis, combining advanced neuroimaging and immune profiling with transcranial magnetic stimulation (TMS).
Exemplar project titles:
- Immunology-focused PhD: “Unravelling effect of brain-driven pain on peripheral immune set point in psoriatic arthritis: an epigenetic and transcriptomic approach”
- Neuroscience-focused PhD: “Targeting the brain to treat pain: mechanistic insights into transcranial magnetic stimulation in inflammatory arthritis”
Professor Stefan Siebert
Professor of Inflammation Medicine and Rheumatology
Stefan.siebert@glasgow.ac.uk
Professor of Inflammation Medicine and Rheumatology
Stefan.siebert@glasgow.ac.uk
I am a senior clinical academic rheumatologist in the School of Infection & Immunity with an active translational research programme in inflammatory arthritis. My specialist clinical areas of interest are psoriatic arthritis (PsA), rheumatoid arthritis (RA) and axial spondyloarthritis (axSpA), as well as related immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease and psoriasis. With colleagues in metabolic medicine, I also have an active research programme exploring the impacts of obesity, and weight-loss (including with GLP-1 receptor agonists) on PsA and psoriasis. Research activities and projects range from studying disease pathogenesis, biomarker discovery to stratify patients and predict treatment response, comorbidities and routine-data linkage, including studying rheumatic conditions across the life course. My work is informed by and focuses on our patients, addressing key areas of unmet need and is done in collaboration with both translational immunology colleagues and clinical colleagues across a range of IMID specialties. My work largely uses data and samples (blood, urine, joint and skin biopsies) from longitudinal observational cohort studies, experimental medicine studies using interventions (eg diet or drugs) to understand disease pathogenesis and human biology using a range of omic technologies, and studies testing the efficacy and safety of interventions in patients with inflammatory diseases.
Exemplar projects:
Potential PhD projects include laboratory-based studies using samples and data from these and other studies to investigate key immune/ metabolic disease pathways and to identify clinically relevant biomarkers in PsA, RA and obesity. There are also more data driven projects using data from existing studies or data-linkage in the trusted research environment (TRE) to investigate key aspects and outcomes of these conditions.
My research is currently focused on understanding immunopathogenesis of rheumatic diseases such as rheumatoid arthritis, psoriatic arthritis and vasculitis, with the aim of translating this knowledge into viable therapeutic agents for patients. Through my leadership of the Translational Immunology programme, I provide the critical interface between clinical and basic science, with a specific focus on precision medicine (the discovery and implementation of biomarkers) and experimental medicine studies.
Professor Mariola Kurowska-Stolarska
Professor of Immune Pathology and Homeostasis
Mariola.Kurowska-Stolarska@glasgow.ac.uk
Professor of Immune Pathology and Homeostasis
Mariola.Kurowska-Stolarska@glasgow.ac.uk
The Myeloid Cell–Focused Tissue Immunobiology Lab, led by Professor Mariola Kurowska-Stolarska at the University of Glasgow’s School of Infection and Immunity, investigates how tissue-resident macrophages and dendritic cells regulate immune homeostasis, inflammation, and disease resolution, using the joint as a model system.
To maximise the impact of tissue discoveries, our lab follows a bedside-to-bench-and-back scientific approach, in which human and mouse research strategies are fully integrated to advance understanding of basic tissue biology and drive clinical innovation. You will be embedded in an ex vivo and in vivo experimental tissue biology lab that is closely linked with the experimental medicine tissue lab at Gemelli Hospital in Rome, led by Professor Stefano Alivernini. This partnership enables a fully integrated basic science and translational research approach within a single project.
To maximise the impact of tissue discoveries, our lab follows a bedside-to-bench-and-back scientific approach, in which human and mouse research strategies are fully integrated to advance understanding of basic tissue biology and drive clinical innovation. You will be embedded in an ex vivo and in vivo experimental tissue biology lab that is closely linked with the experimental medicine tissue lab at Gemelli Hospital in Rome, led by Professor Stefano Alivernini. This partnership enables a fully integrated basic science and translational research approach within a single project.
Exemplar project titles:
- Identifying the cellular and molecular mechanisms that drive the localization of inflammation in joints of individuals at risk of Rheumatoid Arthritis.
- Investigating the role of synovial tissue AXL⁺ DC2 cells in maintaining local tissue and systemic immune tolerance.
- Studying the role of SPP1⁺ synovial tissue macrophages in driving disease flares in Rheumatoid Arthritis patients in remission.
If you would like to discuss these further, please contact tram@glasgow.ac.uk