Charles Institute

The UCD Charles Institute of Dermatology is a purpose built research facility exclusively dedicated to translational research in cutaneous biology. It is the first academic research institute devoted to dermatology in Ireland.  Research in the UCD Charles institute of dermatology addresses common skin diseases such as psoriasis, atopic dermatitis, rosacea, rare genodermatoses and common symptoms such as itch.  The institute’s vision, under the guidance of its director Professor Martin Steinhoff is to become a world leader in dermatology research and training. It aims to achieve this through close collaboration with national and international centers and expertise within the specialty. This will ultimately lead to improved patient care through the discovery and mechanistic understanding of disease processes and the development of new therapeutic possibilities. 

The 2000 m2 research facility provides ample space for up to 72 scientists with access to world-class facilities and infrastructural support. The building bridges the gap between the UCD Health Sciences Centre (http://www.ucd.ie/chs/), Systems Biology Ireland (http://www.ucd.ie/sbi/) and the UCD Conway Institute of Biomolecular and Biomedical Research (www.ucd.ie/conway) where high-end core facilities for transcriptomics, mass spectrometry, proteomics, FACS, cell sorting, molecular biology, neurosciences, state-of-the-art- morphology and imaging are available (http://conway.ucd.ie/coretech/).

The institute is working in partnership with Systems Biology Ireland (SBI) on a number of collaborative projects. SBI designs new therapeutic approaches to diseases based on a systems level, mechanistic understanding of cellular signal transduction networks (combines experiments, bioinformatics, statistics, network modeling with dynamical modeling for systems pharmacology and therapeutics). 

Clinically, the Charles Institute of Dermatology aims to collaborate with national and international dermatology centers interested in participating in translational research in dermatology with a combined goal of improving our understanding of dermatology and ultimately of improving the care of our patients. 

Some areas of research currently underway in the UCD Charles Institute of Dermatology include:

Psoriasis

Psoriasis is a multi-systemic inflammatory skin disease affecting approximately 2% of the population and characterized by well-defined red scaly plaques on the skin. In addition to skin manifestations, the inflammation can also affect joints of patients resulting in psoriatic arthritis. There is currently no cure for psoriasis with treatment modalities aimed at disease control. Our work is aimed at evaluating the pathophysiology and progression of psoriasis in patients and animal models. In conjunction with leading industry partners, we are developing and testing novel therapeutic compounds to alleviate the symptoms associated with specific psoriasis subtypes.

Atopic dermatitis

Pathophysiology and neuroimmune mechanisms of atopic dermatitis:

Atopic dermatitis is one of the most common skin diseases that affect 15-30% of children and 2-10% of adults. In spite of this high prevalence the exact pathophysiological processes underlying the disease are unknown. Recent research has highlighted the importance of not only the immune system but also less well-known factors in the development of the disease. Our research focuses on the complex interactions between the nervous and immune systems, to find previously unknown molecular mechanisms responsible for this common dermatological condition. Understanding the pathophysiology by which this neuroimmune communication occurs will undoubtedly help the development of targeted and mechanism-based therapies against AD.

Itch

Molecular mechanisms of itch

Itch is the most common dermatological condition, affecting up to 8% of the adult population to varying degrees. In spite of it's common nature, true understanding of the molecular pathways activated during itch eludes us. This is especially true in the case of chronic non-histaminergic itch, where conventional therapies are often not effective. By combining novel in vitro, ex vivo and in vivo model systems we hope to find promising new targets for further translational research.

Molecular mechanisms of exocytosis and endocytosis for inflammatory mediators and their receptors

Chronic pruritus is initiated by abnormally upregulated exocytosis (vesicle fusion and release the content) of neuropeptides, cytokines and chemokines etc. In response to their endocytosis (internalization and intracellular routing), a number of the subcellular signaling pathways are activated. Possible consequences include the modulation of functions of puriceptors by elevation of their expression and transportation, as well as augmentation of release of other inflammatory factors. Thus, it is pivotal to pinpoint the key molecular components and understanding the underlying mechanism in the processes of exocytosis and endocytosis in the condition of chronically inflammatory diseases. The gleaned information is used to design and develop novel therapeutics for chronic pruritus. 

Genodermatoses

Epidemiological and Pathophysiological Studies about the Problem of Itch (Pruritus) in Patients with Epidermolysis Bullosa (EB)

Epidermolysis Bullosa (EB) is a family of genetic skin diseases characterized by skin fragility. Its clinical severity varies, with the resultant spectrum of symptoms and complications depending on the genetic subtype. Minor friction or trauma can lead to blistering and wound formation affecting skin and mucous membranes. This may also lead to secondary complications including infection, sepsis, deformities and skin cancer. One very important, albeit poorly understood, symptom in EB is chronic recalcitrant itch (pruritus). Recent publications have highlighted the prevalence and significance of itch in patients with EB where it occurs in 85% of cases. Indeed patients have reported itch as being the most bothersome of their EB symptoms. It results in impaired quality of life, disturbed sleep and complications from scratching. Disapointingly however specific itch treatment with consistent and sustained benefit is lacking. 

By identifying and characterizing key itch pathways, receptors and mediators (neuropeptides, proteases, cytokines, chemokines or growth factors) involved in itch in different EB subtypes, we hope to gain new insights and understanding into the underlying pathophysiology of this severe and distressing symptom. In particular, our human study focusing to identify the key itch pathway(s) important in EB in vivo and ex vivo is the first-of-its-kind and represents an essential first step towards the development of mechanism-based, subtype-oriented therapies in EB.

EB gene therapy

Prof Wenxin Wang and his team are also investigating recessive dystrophic epidermolysis bullosa (RDEB, OMIM ID #226600) caused by a variety of mutations in the COL7A1 gene located on chromosome band 3p21.

This COL7A1 gene encodes type VII collagen, a large (290KDa) elastic structural protein that attaches the epidermal basement membrane to the dermal matrix. The protein is primarily produced by keratinocytes but also by fibroblasts. As collagen is such an integral protein, RDEB affects the skin, eyes and internal membranes. 

Mutations in this gene lead to disruption of the integrity of the dermal-epidermal junction through structurally defective and reduced numbers of anchoring homotrimer fibrils. As a result, friction blisters form easily; some only damaging the top layer of skin but others developing into chronic wounds comparable with third degree burns.

Contact

For queries related to UCD Charles Institute of Dermatology please contact charles@ucd.ie

For all other enquiries, please contact:

Danielle Marie

UCD Charles Institute of Dermatology,
University College Dublin,Belfield
Dublin 4

danielle.marie@ucd.ie

+353 1 7166261

Or visit the website http://www.ucd.ie/charles/