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Blog: Understanding EBS skin and ways to strengthen it

This blog article first appeared on the DEBRA UK website. DEBRA is a national charity and patient support organisation for people living with the rare, extremely painful, genetic skin blistering condition, Epidermolysis Bullosa (EB) also known as ‘Butterfly Skin’. To view the original article, please visit the DEBRA blog page

Professor John Connelly in the lab

Professor John Connelly in the lab

My name is Prof John Connelly, Professor of Bioengineering at Queen Mary University London, UK.

Which aspect of EB are you most interested in?

My laboratory is currently investigating the physical strength and stretchiness (biomechanics) of skin in the simplex form of EB (EBS). EBS is caused by changes in genetic ‘recipes’ for the keratin proteins in the top layer of the skin.  Specifically, we want to understand how these genetic changes alter the physical behaviour of the skin cells (keratinocytes) themselves and their ability to sense and respond to pulling, pushing and pressure forces applied to the skin.  In fact, cells throughout our body are expertly able to sense and respond to these mechanical forces, and this general field of research is known as “mechanobiology”.  While there has been extensive research on the mechanobiology of other diseases, such as cancer, EB has received relatively little attention.

Based on some of my lab’s recent studies, we believe the nucleus of the cell and how DNA is packaged within it are critical components of the cell’s force-sensing ability, and this process is disrupted in EBS where the mechanical properties of skin cells are compromised.  This new research project, jointly funded by DEBRA and Action Medical Research, focuses on determining exactly how force sensing is disrupted in keratinocytes with EBS mutations.  Through this work, our aim is to improve our fundamental understanding of the disease, but more importantly, we want to identify new approaches to treatment and reduce the severity of EBS.  There are some further details about our planned research on the DEBRA website.

What difference will your work make to people living with EB?

We hope that our work will first provide people living with EB a better understanding of their condition, but ultimately, we want to develop new, yet realistic, approaches to improving the symptoms of EBS.  Our strategy in this project is to focus on existing drugs or compounds, which are known to work by altering cell mechanics, and test whether they can improve wound or blister healing in the lab. As some of these drugs are already in clinical trials for other conditions, there could be an opportunity to repurpose some of them for EB, and we think that this approach could allow us to speed up the process of getting treatments to patients.

Who/what inspired you to work on EB?

My interest in mechanobiology was first inspired by Prof Marjolein van der Meulen, who studies bone adaptation to mechanical forces.  I worked in Prof van der Meulen’s lab as an undergraduate student at Cornell University and was inspired by her incredible enthusiasm for science and the overall concept that tissues in the body are regulated by more than just biological substances - physics and mechanics are also crucially important.

For several years, the main focus of my own lab’s research was to understand how mechanical forces regulate normal cell function in the skin.  My team and I have mapped out some of the key ways that cells sense mechanical forces, and now we would like to apply this knowledge to understanding and treating skin diseases. EB is a particularly devastating condition for children and families, and since EB is a mechanically-based disease, we hope that our expertise could help make a real impact on the treatment and management of EB.  We have already been inspired by the bravery of children and adults living with EB and by the commitment of their families and charities like DEBRA to finding treatments and cures to improve the lives of patients.

What does the funding from DEBRA mean to you?

We are incredibly grateful to DEBRA and Action Medical Research for funding this project and allowing us to take forward some of our new ideas in this area.  There are currently limited opportunities for research funding in rare genetic skin disease, and DEBRA is the only charity to specifically fund EB-related research.  This project will therefore be a great opportunity to translate our fundamental knowledge in biomechanics to EB, and hopefully we can make a positive contribution to helping people with EB.

What does a day in your life as an EB researcher look like?

As the principal investigator for this project, my role is quite varied.  I spend much of my time meeting with researchers in the team to plan experiments, review findings, and discuss their implications.  I also work with our collaborators to get their input on the project.  Finally, I spend a fair amount of time writing manuscripts and grant proposals, and I teach undergraduate and postgraduate courses here at QMUL.

Who’s on your team and what do they do to support your EB research?

John Connelly's team photo

For this new project, we have recently recruited a new postdoctoral scientist, Dr Emily Lay, who joined the team in September 2023.  Emily completed her PhD from the University of Bath and will be the primary scientist working on this new project.  She brings expertise in growing different skin cells in layers to mimic the complex structure of our skin (3D cell culture models), skin biology, and gene sequencing.  She will also be supported by Yiyang Guo, who is a technician in the team and will be assisting with growing the skin cells and studying them under the microscope, and by Dr Liisa Blowes, who manages our 3D bioprinting facility and will assist with development of 3D cell culture models of EBS.

How do you relax when you’re not working on EB?

In my downtime, I enjoy long distance running, and I find this is a great way to take a break from work and get a bit of exercise outdoors.  As DEBRA is affiliated with a number of runs and challenges, I am hoping to get involved in one of the upcoming races and help raise some money for the charity.



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