Differences between the surface inside the mouth and the skin on the outside of the body may hold the key to understanding scarless healing and cancer development in RDEB. This could help to prevent EB wounds progressing to chronic wounds or cancer. 

 

Dr Inês Sequeira works at Queen Mary University, London, UK on this project to understand scarless healing and cancer resistance in DEB. Wounds in the mouth should heal quickly, but this is not the case in DEB. However, even people with DEB rarely get cancers occurring inside their mouths. By comparing cells lining the mouth in people with and without DEB and by comparing mouth lining to skin, this project hopes to identify ways to help EB wounds heal and prevent them from progressing to non-healing chronic wounds or cancer.

 
Contents:

• Project summary (top of page)
• About our funding
• Latest progress summary
• About our researchers
• Why this research is important
• Researcher's abstract
• Researcher's progress update

 

About our funding:

Research leader	Dr Inês Sequeira
Institution	Queen Mary University London (QMUL), UK
Type of EB	RDEB
Patient involvement	Tissue biopsies during routine oral surgery
Funding amount	£199,789.17 co-funded with DEBRA Ireland
Project length	3 years
Start date	TBC 2024
DEBRA internal ID	GR000038

 

Latest progress summary:

Due 2025

 

About our researchers:

Lead researcher:

Dr Inês Sequeira is a Senior Lecturer/Associate Professor in Oral Cancer and Deputy Director of Research at the Institute of Dentistry in the Blizard Building at Queen Mary University London. As a Stem Cell biologist for more than 18 years, she has dedicated much of her research career to studying skin and oral epithelia homeostasis, wound healing and cancer. She is currently involved in the global effort of mapping all the cells of the human body through the Human Cell Atlas (HCA) initiative and coordinates the Human Cell Atlas Oral and Craniofacial Biological Network focused in understanding the oral mucosa cell heterogeneity. Her team’s research focus in understanding the scarless potential of the oral mucosa when compared to skin, and in dissecting the cellular and molecular heterogeneity of oral squamous cell carcinomas. Dr Sequeira is highly engaged in science outreach, writing for several outreach blogs, producing a podcast on stem cell research, working in collaboration with artists and architects to develop art installations, organising lab visits for school children and giving talks in schools. Based on these networks and experience, she will work with the local community to share findings from her research.

Co-researchers:

Dr Christina Guttmann-Gruber and Dr Josefina Piñón Hofbauer are group leaders and principal investigators at the EB House Austria, an EU reference Centre of Excellence for patients with epidermolysis bullosa. 

Dr Su Mar Lwin is a dermatology registrar and a Group Leader at St John’s Institute of Dermatology, Guy’s and St Thomas’ NHS Foundation Trust and King’s College London, respectively. Dr Lwin has more than nine years’ experience in translational research in monogenic skin diseases; she is GCP (Good Clinical Practice) and HTA (Human Tissue Act)-trained, and Principal Investigator on a pre-clinical study to develop a novel spray-on ex vivo gene therapy for RDEB. 

Dr Mirjana Efremova is Lecturer and Group Leader at the Bart’s Cancer Institute. Dr Efremova is a bioinformatician with extensive experience in data analyses of single-cell multi-omic data and is involved in the data analysis of the Skin Cell Atlas (Human Cell Atlas project). She co-developed the receptor:ligand cell-cell interaction tool CellPhoneDB and data integration algorithm MultiMap. 

   

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Why this research is important:

If you are an RDEB patient, you live with the impending threat of cancer. There is an acute need to translate our understanding of RDEB biology into an ability to detect, predict, or prevent the degeneration of an acute wound into a non-healing fibrotic site and into a tumour.

Dr Inês Sequeira

 

Researcher’s abstract:

Grant title: Identifying the cellular and molecular mechanisms underlying the oral mucosal scarring and resistance to cancer development in RDEB patients.

If you are an RDEB patient, you live with the impending threat of cancer. There is an acute need to translate our understanding of RDEB biology into an ability to detect, predict, or prevent the degeneration of an acute wound into a non-healing fibrotic site and into a tumour. Our strategy to address this need, is to look at wound healing and cancer formation from the unique perspective of a tissue (oral mucosa) that normally heals very well. This ability is lost in RDEB oral mucosa, which nonetheless shows some resistance to tumour development compared to skin. Therefore, this tissue may hold a key to understanding what’s needed to promote wound healing and to prevent cancer. Yet, research on the oral mucosa in EB is sparse. We intend to make up for this by applying modern methods that allow us to maximise information gain from an individual tissue sample, and therefore be respectful of a patient’s disease burden. We will contextualise the data against large published and unpublished datasets from healthy paediatric and adult individuals, which we have access to as network leader within the Human Cell Atlas consortium, and from other inflammatory tissues. This means that we have the best chance of gaining biological insight from a limited number of patient samples. Our data will potentially highlight cell programs that can be targeted for therapy in a next phase of research. We will make our data widely available to support further research by the EB community.

In healthy individuals, wounds in the mouth (oral mucosa) heal rapidly and without scarring. However, in RDEB, patients suffer from non-healing wounds and profound scarring of both skin and oral mucosa. By studying the stark differences in wound healing between the oral mucosa of healthy individuals and RDEB patients, we can uncover clues as to what is needed for scarless healing. This will be accomplished using state-of-the-art technologies that enable us to identify the different cells that make up a tissue (i.e. cellular composition), and give insight into what those cells are doing (i.e. cell state). Additionally, while RDEB patients are prone to the development of skin tumours, oral tumours rarely develop in these patients, suggesting an inherent resistance to cancer formation of the oral mucosa that could be related to the different cell types, cell states, and inflammatory state present in the mouth versus skin. By comprehensively studying the cellular composition and cell state of the mouth and skin, we can identify cellular and molecular factors that contribute to scarless healing and cancer resistance, which is a prerequisite for the design of effective therapies to improve wound healing, prevent scarring and cancer formation in both skin and the mouth in RDEB patients.

 

Researcher’s progress update:

Due 2025.

 

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Image credit: Kamaji Ogino (Pexels)