Current Research Programmes

The Psoriasis Association is currently funding research into the following studies.

The 2017 research grant application process is now closed. For more information, please get in touch with us.

The role of IL-1 and IL-36 in palmar plantar pustulosis (PPP)

Dr Francesca Capon, King's College, London

What is already known about the problem that the project will address?

Palmar plantar pustulosis (PPP) is a severe form of psoriasis manifesting with the appearance of painful pustules on the palms and soles. These lesions can be preceded or accompanied by plaque psoriasis and/or psoriatic arthritis. PPP is a disabling condition that has a profound effect on quality of life, as affected individuals can find it very difficult to walk or carry out everyday tasks. At the same time, very little is known about the causes of the disease, which as a consequence is extremely difficult to treat.

What do you hope to find out?

The aim of our research is to achieve a better understanding of the causes of PPP, as that is essential for the development of effective treatment. Our group has already discovered two genes that malfunction in affected individuals, causing excessive production of an inflammatory molecule known as IL-36. Importantly, we also demonstrated that IL-36 drives the release of a protein called IL-1, which can be blocked by existing drugs. This was a breakthrough, which suggested that PPP could be treated with known IL-1 inhibitors.

It is important to bear in mind, however, that the genetic defects we have discovered are only found in 10-15% of individuals with PPP. Therefore, it is still not clear whether abnormal release of IL-36 and IL-1 is a general feature of the disease.

With this project, we plan to identify novel PPP genes and to establish whether they also cause excessive IL-36 and IL-1 production. If we find that the newly identified defects do not alter IL-36/IL-1 levels, we will seek to clarify what are the alternative mechanisms whereby they cause disease.

Mutation burden of narrowband UVB

Professor Eugene Healy, Southampton University

Ultraviolet radiation (UV) in sunlight is an effective treatment for psoriasis.  Narrowband UVB (NB-UVB) is a form of “artificial sunlight” which is used widely by dermatologists to treat patients with psoriasis.  It is known that UV can cause skin cancer, but the long-term safety of NB-UVB in relation to skin cancer development is unknown.  It has been highlighted that, in order to determine the long-term safety of NB-UVB, large studies in multiple dermatology centres involving several thousand new patients per year would need to be conducted and that those patients would need to be followed up at least for 10 years or more.  In the meantime, patients with psoriasis and dermatologists do not know what is a suitable safe limit of NB-UVB treatments for people with psoriasis to have over the course of their lifetime.

All of the cells in our body contain the genes that we are born with.  These genes are written in the DNA in all our cells, including our skin cells.  Exposure of the skin to UV causes specific damage to the DNA in skin cells and leads to mutations (i.e. errors in the DNA) that affect the ability of the genes to work properly.  When a skin cell divides these changes are passed on to its daughter cells.  Over time, these daughter cells and their descendants (which are collectively known as a clone) may eventually accumulate thousands of mutations which may cause the skin cells to become abnormal and form skin cancers.  Recent advances in genetic technology have allowed scientists to map groups of cells carrying altered genes which drive the formation of cancer in normal skin.  In the proposed study, we plan to use this technology (called next generation sequencing) to detect how many groups of cells carrying DNA changes linked to cancer are induced by NB-UVB treatment for psoriasis.  Based on these findings, we will calculate the additional risk of cancer in a psoriasis patient resulting from multiple courses of NB-UVB and thus estimate the long-term safety of NB-UVB.

The risk of cancer in psoriasis patients treated with biologic therapies compared with conventional systemic therapies: results from the British Association of Dermatologists Biologic Interventions Register (BADBIR)

Dr Richard Warren, University of Manchester

Patients with severe psoriasis (more than 10% of the body surface affected) are often offered two broad types of long-term systemic treatment: conventional systemic treatments, such as methotrexate, ciclosporin and acitretin; and biologics, such as Humira, Stelara, and Enbrel. Biologic therapies target the immune system and may affect the body’s ability to fight cancer. It is not known whether being treated with biologic therapies carries an increased risk of cancer in psoriasis patients compared to treatment with conventional systemic treatments. Very few studies have compared the safety of these two treatment options and have been limited by short duration with only small numbers of patients. As cancers develop relatively rarely, we need to compare large groups of psoriasis patients receiving biologic and conventional systemic treatments respectively.

A pilot study to compare the response of psoriasis to narrow-band UVB phototherapy in the morning and afternoon

Dr Henry Grantham, Royal Victoria Infirmary, Newcastle Upon Tyne

Psoriasis is a very common skin disease. We often think of psoriasis as a disease of just the skin, but research shows that people who have psoriasis may have different body clock rhythms from the general population. We know that people without psoriasis are more sensitive to phototherapy with ultraviolet B light at different times in the day. What we don’t know is if this is also true for people who have psoriasis.

The main aim of this research question is to see if patients' psoriasis is more sensitive to ultraviolet light at different times of the day.

We also aim to see whether the participants in our study have different body clock (circadian) rhythms to the general population. We will do this in multiple ways, such as looking at the levels of a few chemicals in the body that respond to body clock rhythms (melatonin and cortisol), asking questions about participants' sleep (by questionnaire), measuring sleep (with a wrist-worn motion sensor), and asking the patients to fill in questionnaires about depression.

We will recruit 15 patients who have been prescribed phototherapy for the treatment of their psoriasis. The study will last nine days per patient and after this they will proceed to their prescribed course of phototherapy.

Not just skin deep: circulating lipids in a "localised" disease

Dr Timothy M Millar, Southampton General Hospital

People with psoriasis have a greater risk of clogged arteries and heart disease than the general population. People with psoriasis show more bad cholesterol and less of the good kind circulating in the blood. This can lead to fatty plaques growing on the inside of the blood vessel wall which are filled with white blood cells.

Plaque psoriasis shows large numbers of white blood cells in the skin and an over growth of blood vessels. We believe that the plaque form of psoriasis and the fatty plaques seen in the blood vessels have striking similarities.

From our earlier research, we have shown that some types of fat found in the blood can control new blood vessel growth. New blood vessel growth is part of how plaques form in psoriasis and more blood vessels mean more white blood cells. These white blood cells in turn can cause blood vessels to grow causing a vicious circle of continued plaque flares.

We have also shown that some white blood cells have the potential to be activated by blood fats and that when fats are removed, more white cells die. While some current treatments for psoriasis show effects on blood lipids they still have side effects which could be improved on. Together with other chemicals which are raised in psoriasis, these blood fats could provide a simple target to help treat the skin disease and also reduce the risks from clogged arteries.

It is likely that our approach would provide an additional treatment to those already in place. It would mean that traditional treatments can be scaled back which would benefit patients with potentially fewer side effects. There is also the added benefit of reducing blood vessel diseases and improving quality of life through gains in fitness. These fat restricted nutritional approaches are achievable today but knowledge of the best mix of dietary fats is a medium term goal. More long term outcomes would be small drug treatments targeting fat dependent processes.

An innovative mixed methods study investigating altered emotional processing in psoriasis patients

Dr C. Elise Kleyn, University of Manchester

Psoriasis is a chronic, inflammatory skin disease which affects 2-3% of the UK population. As a result of the appearance of their skin, patients with psoriasis commonly experience negative social interactions and reactions from others including facial expressions of disgust.

Our group were the first to use brain scanning (magnetic resonance imaging) to demonstrate that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease. It was demonstrated that patients with psoriasis have a diminished signal in the insula, an area of the brain known to be important in disgust processing. This differential response may reflect a coping mechanism, adopted by patients to ‘block out’ the aversive reactions of others and protect themselves from stressful emotional responses. 

More recent, (unpublished) work, by the group suggests that an individual’s response to disgust may vary depending on the length of time a patient has had psoriasis and the age at which they were diagnosed. However, it is not known when this mechanism develops, or its wider implications on patients’ quality of life.

This novel study will pilot the integration of different techniques, including in-depth patient interviews and state-of-the art brain scanning, to further understanding of this proposed coping mechanism in psoriasis. Addressing this current gap in knowledge will inform the development of personalised clinical and psychological interventions to support people living with psoriasis.

The role of mast cell tryptase in psoriatic itch

Professor Silvia Bulfone-Paus, University of Manchester

Psoriasis is a chronic, frequently life-ruining skin disease in which itch is one of the least understood – but one of the most frustrating – symptoms.

The sensation of itch in psoriasis patients is unique and different to that of other skin diseases: an intense burning / biting sensation, which is often enhanced by stress and can often be experienced in the absence of active skin disease. Additionally, scratching can lead to a worsening of disease. There is therefore a need to explore the origins of so called “psoriasis itch” to develop more effective treatment strategies.

This PhD project will investigate chemicals produced by mast cells (a critically important cell type in psoriasis) and how they interact with other cells in the skin to produce the characteristic itching. This study promises to clarify the role of mast cells in psoriasis and may ultimately lead to more effective strategies for the management of psoriatic itch.

Characterization of novel pathogenic pathways for generalised pustular psoriasis

Dr Francesca Capon, King's College, London

Generalised Pustular Psoriasis (GPP) is a rare, but potentially life-threatening variant of psoriasis that is notoriously difficult to treat.

Our group has been leading the search for the genetic causes of GPP and has identified two genes, which account for a significant proportion of disease cases. We now plan to build on these exciting findings to gain a better understanding of the mechanisms that underlie the onset of GPP symptoms.

We will achieve this objective through a multi-disciplinary approach integrating genetic studies and computational methods. This innovative strategy will allow us to uncover additional genes that are abnormally active in the immune cells of GPP patients and therefore play an important role in determining disease onset.

These studies are expected to facilitate the identification of novel GPP genes and to shed new light on the mechanisms that can be targeted for the treatment of this severe disorder.

A role for connexin-mediated signalling events in the pathogenesis of psoriasis

Dr Patricia Martin, Glasgow Caledonian University

During psoriasis, skin cells multiply and their ability to stick to one another is affected, resulting in ‘flaky’ skin and inflammation. A change in the bacteria that live on the surface of the skin during psoriasis may also influence this process.

We will investigate how a family of proteins, the connexins, that enable skin cells to i) talk to one another and ii) stick to one another are modified during psoriasis and by microorganisms present on the skin.

Connexin26 is found at very high levels in the skin of psoriasis patients yet the level of its sister protein Connexin43 is reduced. Agents that can ‘block’ overactive Connexin26 may decrease inflammation, and agents that stabilise Connexin43 may encourage skin cells to stick together thereby reducing the symptoms of psoriasis. Skin cells isolated from ‘normal’ and ‘psoriatic’ skin samples will be used.

Such an approach may identify new treatments for psoriasis.

Psoriasis and sleep deprivation

Dr Chris Bundy, University of Manchester

Psoriasis is a chronic inflammatory skin disease that affects 1 in 50 people in the UK. It occurs as red, scaled patches particularly on the scalp, elbows and knees and is currently incurable.

Stress is known to both trigger and worsen psoriasis in some patients. The appearance of psoriasis and the scaling can be very distressing; some patients say the itch and soreness of plaques stops them sleeping well. We don’t know how widespread the problem is.

Lack of sleep can affect mood and ability to work and function in the day time. This aspect of psoriasis is under-recognised by health care staff and consequently is poorly managed.

This project will: (1) comprehensively assess whether sleep disturbance is a significant problem in people with psoriasis; and (2) test an existing on-line method to improve sleep quality in people with psoriasis.

In July 2017, an article from this study was published in the British Journal of Dermatology (BJD). You can read a summary here.

Neuropsychological morbidity in psoriasis

Dr Elise Kleyn, University of Manchester

Psoriasis is a chronic skin disease for which there is currently no cure. It afflicts far more than the skin and there is limited knowledge of the mechanisms or way in which psychological effects as well as other brain effects are caused.

We were the first to use brain scanning techniques to show that patients with psoriasis process facial expressions of disgust differently to individuals without skin disease.

This PhD project will use state-of-the-art brain scanning, questionnaires and laptop-based tasks to investigate whether treating psoriasis lesions effectively will change altered processing of disgust in patients. Patients’ reactions to pictures of their own psoriasis lesions and those of others will also be studied in a separate group of patients who have had psoriasis for varying lengths of time.

Understanding the brain-skin connection is key to developing new approaches to help treat the psychological and other brain effects of psoriasis.

Functional characterisation of genetic susceptibility to psoriasis

Dr Julian Knight, Oxford University

Recent genetic advances offer unique opportunities to improve our understanding of the causes of psoriasis and improve patient care.

There is now evidence of association between particular genetic differences between people and risk of disease. However these associations do not tell us which genes are associated with disease, how genetic variants act and how this is relevant to patients.

This studentship will aim to carry out research to address these questions using cutting-edge techniques applied to patient samples. The longer-term aim will be to provide a better understanding of psoriasis and identify pathways that could serve as drug targets or biomarkers for diagnosis and prognosis. The studentship provides a unique training opportunity for a future research leader in the field, building research capacity.

The research supervisors, Julian Knight and Graham Ogg are both clinical academics at the University of Oxford with research expertise spanning genetics and the biology of psoriasis.

An investigation into genetic factors which discriminate psoriasis from psoriatic arthritis 

Dr Richard Warren, University of Manchester

Psoriasis is complicated by an arthritis, known as psoriatic arthritis (PsA) in approximately 25% of cases.

It is well known that patients who have psoriasis affecting the skin and those who go on to develop the joint problems often have affected family members, what we would call a genetic predisposition to the condition.

What is not understood is which genetic factors (small changes in an individual's DNA code) influence who will develop psoriasis that remains confined to the skin versus those individuals who will also develop the arthritis.

This study will involve a large scale genetic investigation comparing and contrasting the genetic makeup of individuals from these 2 sub-groups. A greater understanding of the genetic factors which influence these two potential outcomes would be very helpful in: 1 – trying to devise ways to prevent the onset of PsA; and 2 – target specific individuals with more appropriate treatments.

The Psoriasis Association is the UK's leading national charity and membership organisation for people affected by psoriasis – patients, families, carers and health professionals Read More >

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