Clinical Primer Award

Principal Investigator: Dr Chantelle Wiseman
School of Medicine

Post-traumatic stress disorder (PTSD) occurs in about 20% of individuals who experience a significant traumatic event (eg sexual assault). People with PTSD have repeated memories and nightmares about the event, which are very distressing and interfere with their relationships and their ability to work or function normally.

It is not clear why some people develop PTSD after a traumatic event, whilst others do not. A better understanding of what makes some people more likely to develop PTSD would help to identify those at greatest risk. They could then be followed up more closely, and receive help earlier to prevent PTSD from developing.

The aim of this study is to examine whether certain characteristics during early development influence risk of developing PTSD. I will examine whether personality traits during childhood and adolescence, the type of parent-child relationships whilst growing up, and problems with social cognition (that measures the way we think about and relate to other people) in adolescence influence the likelihood of developing PTSD after exposure to a traumatic event. I will use data that has already been collected in a large birth-cohort study to establish whether these characteristics can help to identify people at greatest risk of developing PTSD.

Principal Investigator: Dr Bnar Talabani
School of Medicine

Diabetes consumes approximately 10% of total NHS resources. Diabetic Kidney Disease (DKD) affects 40% of people with diabetes, remaining the commonest cause of kidney failure in the UK and leading to increased mortality. While good control of blood-sugar and blood-pressure can slow the decline of kidney function, we are unable to stop or reverse it. Macrophages are immune cells important in the control of infection and injury.

Recent advances suggest that Macrophages are important drivers of DKD. Understanding the behaviour of these cells, and how they may contribute to the development of DKD is a central focus of this application. I will capitalise on advances made in Cardiff and Bristol Universities that have (1) developed new, world-leading  approaches to studying subsets of tissue macrophages and (2) developed experimental models of DKD that closely model the pathology. I plan to identify and purify different types of kidney macrophages, and to perform an unbiased profiling of their gene expression patterns.

I expect these studies to delineate the transcriptional regulatory network underpinning renal macrophage biology in DKD, which I intend to study in depth. Ideally, this will lead to improvements in early diagnosis, stratification and treatment of patients likely to develop DKD.

Principal Investigator: Dr Zoe James
School of Medicine

Traumatic brain Injury (TBI) is a growing health and socioeconomic problem that effects many people worldwide. The damage incurred can be severely debilitating, primarily affecting younger populations, and can result in the requirement for life long care. TBI occurs in two stages; the first stage is the primary insult, which disrupts the structural architecture and triggers brain inflammation. Inflammation then induces a secondary stage of injury that results in the cognitive and behavioural deficits seen in TBI patients. However, this stage does not become irreversible until some time after the initial injury.

This may present a window of opportunity for therapeutic interventions aiming to improve outcomes subsequent to TBI. A significant increase in the levels of a protein called High-mobility group box-1 (HMGB1) has been observed in the blood and the brain of patients sustained TBI. HMB1, a key player in the secondary injury, acts as a ‘danger signal’ to intensely trigger port-TBI brain inflammation. In animal studies

Principle Investigator: Dr Jack underwood 
School of Medicine

Autism Spectrum Disorders (ASD) are a group of developmental disorders characterised by persistent difficulties in social interaction, communication, restricted interests, stereotypic behaviours and resistance to change. Estimates suggest around 1% of the population have ASD to some extent, with a male to female ratio of approximately 3:1.

Most research to date has looked at the more severe presentations of ASD and been focussed on children. Past research has shown that people with milder forms of ASD may not come to the attention of services or be aware of their difficulties with social interaction until they are adults. An increasing number of specialist services for these adults are being set up throughout the UK. Very few studies look at how adults with ASD live or why they present to clinical services for diagnosis.

This study will examine the lifestyle, social demographics and other mental and physical health problems of a population of adults diagnosed with ASD. Using data held in a national anonymous databank of health records I aim to establish how the lives of adults with ASD differ from the general population. This will provide information for consultations in specialist adult clinics, and clues to the biology behind ASD.

Principle Investigator: Dr Mark Ponsford
School of Medicine

Schizophrenia is a common and devastating mental illness affecting 1% of the population. Clozapine was licensed as therapy over 30 years ago and remains the only effective anti-psychotic therapy for patients with treatment-resistant schizophrenia. Despite saving lives by reducing suicide risk, people taking clozapine are at increased risk of chest infections.

I recently led a study which showed that patients on clozapine therapy typically display low levels of antibodies (known as “IgG”, “IgA”, and “IgM”) in the blood. These proteins are important for the neutralisation of bacteria and viruses, and this response may explain the increased incidence of infections associated with clozapine. This outcome is rarely seen with other schizophrenia drug-treatments. This supports a unique mode of action for clozapine that may be useful in the treatment of immune-mediated diseases (e.g. rheumatoid arthritis).

This grant will support new insights for how clozapine controls antibody production. I will use experimental model systems where antibody generation is required for the development of inflammatory disease. Thus, this project will identify how clozapine disrupts control of the immune system and will establish whether this anti-psychotic drug may have wider applications in the treatment of immune-mediated diseases (e.g. Rheumatoid arthritis).