The Oliver Thomas EB Fellowship will train a new scientist specialising in EB research and provide important developments in EB therapies. They will achieve their PhD by studying whether existing drugs can reduce EB blisters caused by immune system proteins and cells. 

A black and white photo of a smiling person wearing glasses

Dr Chambers works at the Blizard Institute (QMUL) and will supervise a PhD student to carry out this work on immune cells and proteins in JEB skin.  Drugs such as Anakinra, Infliximab and Entanercept, are already in use to stop the damaging effects of immune system proteins called interleukin-1 (IL-1) and TNF. This work will confirm that these proteins contribute to the symptoms in EB skin and test whether the existing drugs can reduce these symptoms. Additionally, immune system cells in EB skin samples will be investigated to see if they are responsible for producing the increased levels of these damaging proteins. The results could be relevant for other types of EB because immune system proteins are involved in all types of EB.

 

Contents:

 

About our funding:

Research leader Dr Emma S Chambers
Institution Centre for Immunobiology, Blizard Institute, Queen Mary University of London
Type of EB JEB
Patient involvement No
Funding amount £139,912.38
Project length Non-clinical PhD studentship - 4 years
Start date TBC 2024
DEBRA internal ID GR000048

 

Latest progress summary:

Due 2025.

 

About our researchers:

Lead researcher:

Dr Emma Chambers is a Lecturer in Immunology based in the Blizard Institute and has more than 10 years research experience in translational immunology with a particular focus on cutaneous immunity. Dr Chambers obtained her PhD at Kings’ College London and subsequently was a postdoctoral fellow in the lab of Professor Arne Akbar at University College London leading to a number of high impact publications. 

Co-researchers:

Dr Matthew Caley is a Senior Lecturer in Cell Biology (Blizard Institute) with more than a decade of experience in skin research, matrix biology and generating in vitro skin models. Dr Caley is a committee member of the British Society of Investigative Dermatology (BSID) and a founder of the national Skin Microbiome in Healthy Ageing (SMiHA) research network. 

Dr Emanuel Rognoni is a Senior Lecturer (Blizard Institute). During his PhD he focused on the EB subtype Kindler Syndrome where he revealed a novel function of the integrin binding protein Kindlin-1. Later, he further specialized in skin research, investigating how different dermal fibroblast subpopulations organize and influence each other during development and wound healing in Prof Fiona Watt’s lab (KCL). Using genome-wide sequencing technologies, innovative 2D/3D culture platforms and skin transgenic/disease models, his group at QMUL is now uncovering the molecular mechanisms and implications of fibroblast heterogeneity in skin health, regeneration and disease. 

 

Why this research is important:

The aim of this project is to understand the how IL-1 and TNF drive blister pathology in individuals suffering with JEB – with an ultimate aim to repurpose current therapies to improve the health-span of individuals suffering from JEB.

 Dr Chambers

Researcher’s abstract:

Grant title: Dissecting The Role Of Inflammatory pathways In Junctional epidermolysis bullosa (JEB) Pathology.

Junctional epidermolysis bullosa (JEB) is a rare genetic skin disease leading to widespread blistering and impaired wound healing. This debilitating disease is not curable, with current therapies treat the symptoms of the disease. Therefore, identifying how and why the disease develops and which signalling pathways are involved will open novel therapeutic targets. We have identified from an inducible model of JEB that the inflammatory cytokines Interleukin-1 (IL-1) and Tumour Necrosis Factor (TNF) are greatly increased during blister formation. The source of these cytokines has not been elucidated - however there is an accumulation of mononuclear phagocytes, as identified by the marker F4/80 – indicating that macrophages are a key cell in driving the inflammatory blister formation. The overarching aim of this project is to dissect the role of macrophages and inflammatory cytokines IL-1 and TNF in JEB blister pathology – with an ultimate aim to identify novel therapeutic targets to facilitate drug repurposing for JEB. For this PhD studentship we will investigate the time-course of IL-1 and TNF cytokine production and determine the cellular source (Aim 1) utilising flow cytometry and microscopy techniques. Subsequently, data from the inducible model will be validated in the human JEB skin organotypic model which has been previously optimised (Aim 2). Finally, anti-IL-1 and TNF therapies will be utilised in the JEB model to determine if they reduce disease pathology (Aim3).

 

Researcher’s progress update:

Due 2025.