By Dr Daniele Castiglia

My name is Daniele Castiglia. I am a molecular geneticist, and director of the Laboratory of Molecular and Cell Biology at Istituto Dermopatico dell’Immacolata (IDI-IRCCS) in Rome, Italy.

 

Which aspect of EB are you most interested in?

The common goal of my group at the IDI-IRCCS and our colleagues at the Bambino Gesù Children’s Hospital (OPBG) is to understand fibrosis in recessive dystrophic epidermolysis bullosa (RDEB). Fibrosis is the name for the process by which cells produce fibres of sticky protein to heal wounds. It’s like the body’s natural way of sticking bandages over an injury. The more often injuries happen, the more layers of ‘protein bandages’ our cells produce through fibrosis. This helps wounds close, but the repairs (scars) are not quite as good as new because the scarred skin can be thicker and less flexible than it was. Sometimes cells continue the process of fibrosis when they should stop – they are ‘deregulated’. This can do more harm than good and make RDEB symptoms worse. Over time, these deregulated skin cells may cause cancer to develop. By finding out more about how skin cells regulate the process of fibrosis, we may be able to develop new treatments to keep skin working better for longer and delay the onset of cancer.

We can take a small piece of skin (a biopsy) and grow skin cells, called fibroblasts and keratinocytes, from it in the laboratory. We use cells from people living with RDEB and also from people without EB to compare the RDEB skin cells to. Having EB and non-EB skin cells growing in our laboratory is called a ‘model’. It allows us to study how EB cells behave differently and find treatments that help them to work more like the skin cells from people without EB. A model like this is very useful to try out different therapies long before they are given to people living with EB. Evidence about how potential treatments work and how well they work can be collected.

Additionally, our research groups are interested in matching the symptoms a person experiences to the specific genetic change that causes their EB. This is useful for people to predict how their EB symptoms might progress when they find out what change they have but may also highlight ways that we could treat those symptoms.

 

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

RDEB is caused by a lack of a protein called collagen VII. When skin is made without this protein, it is very fragile and people suffer blistering, itching and painful wounds that are slow to heal. We’re working to understand how this affects skin cells and to choose which existing drugs could be repurposed to delay these symptoms. We can try out our chosen drugs on the cells (fibroblasts) in our laboratory to gather evidence that they work. By slowing down fibrosis, we hope to improve the quality of life of people living with RDEB.

 

Who/what inspired you to work on EB?

In 1995, I joined Dr Giovanna Zambruno's Laboratory at IDI-IRCCS as a research assistant. At that time, a large group of people living with EB were being cared for in our hospital. They, and their dermatologists, had high expectations from the Laboratory of Molecular and Cell Biology, then run by Giovanna (or Gianna, as she prefers to be called) and later by myself. In particular, there was a lot of work to be done on classifying EB subtypes and linking them to the exact genetic change that causes them. We also provided genetic counselling for families to explain what their genetic diagnosis would mean for them and their children and researched the development of possible new therapies. After having directly known the families and listened to the experiences of both those living with EB and their caregivers, I decided to do something useful for them.

I have never regretted this decision and now, close to retirement age, every small step forward in my research reaffirms my original choice.

 

What does the funding from DEBRA UK mean to you?

I consider it a privilege to have the support of such a strong and determined charity as DEBRA UK that has always been there to appreciate my proposals and to recognize their significance. This has helped me to gain confidence in myself and to find new motivation. DEBRA UK’s financial support has been key to carrying out our research.

 

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

As a longstanding EB researcher and laboratory manager, each day in the laboratory uses my knowledge and experience. I spend time discussing results and their meaning and offering colleagues potential solutions and steps forward when they encounter challenges. A very important part of my work revolves around people living with EB and involving them in our research.

 

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

Almost all my work on EB is the result of a well-established collaboration between my laboratory at the IDI-IRCCS and Dr May El Hachem's Genodermatosis Research Unit at OPBG where Gianna now works. In addition to the clinical-molecular experience on EB that Gianna and I have, the EB research work in these two laboratories has benefited from the enthusiasm and new ideas of Dr Angelo Condorelli, the architect and first author of our recently published study in the Journal of Investigative Dermatology (Condorelli AG et al, 2024). Crucial to our EB research has been the expertise of Dr Teresa Odorisio, a senior scientist at IDI-IRCCS. Importantly, our long-term collaborative efforts have allowed us to overcome difficulties related to having only small amounts of skin samples and so few people living with RDEB who can be involved in our research.

 

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

I like to discover other lives by reading novels, going to the cinema and theatre, and walking with my dog. I also like very much to stand in front of the sea. There, happiness is a simple idea (J-C Izzo).

 

What these words mean:

Molecular geneticist = Someone who studies the sequences of DNA molecules.

Genetic counselling = providing information about how a genetic change might affect you or your family.

Model = a way of testing treatments before they are offered to people.

 

Full glossary of scientific terms