By Dr. Carina Graham

My name is Dr. Carina Graham, and I’m a postdoctoral researcher in the laboratory of Dr Joanna Jacków-Malinowksa based at St John’s Institute of Dermatology, King’s College London.

 

Which aspect of EB are you most interested in?

My top interest is to improve quality of life for people living with EB, specifically dystrophic EB (DEB). In second place I am interested in the opportunity to create a technology that can be applied more universally. A topically applied DNA editing treatment would be enormously beneficial to all types of EB and all kinds of inherited skin diseases. It sounds like science fiction, but we hope to be among the first researchers to make it a reality!

 

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

A specific glue-like protein is meant to stick the layers of your skin together. The skin cells of people living with DEB are unable to make this protein glue due to errors in their DNA. DNA essentially instructs your cells how to build proteins, and mistakes in the DNA interfere with this – imagine trying to build Ikea furniture using instructions that are full of mistakes! When this happens, the layers of skin can slide apart from one another very easily and the symptoms of DEB occur.

The current cutting-edge DEB treatment, B-VEC, essentially delivers this protein into the skin. However, the protein wears off over time, so you have to reapply it over and over. Our DNA editing treatment would teach skin how to make its own protein, so you’d only need to apply it once, and the skin would stick to itself on its own from then on. Therefore, this treatment is a “one and done” cure that corrects the underlying cause of DEB. Because it replaces the entire gene (i.e. the entire instructions booklet for that particular protein), it doesn’t matter where the genetic change is in the DNA – any DEB patient would be able to receive this treatment.

Because there are a lot of safety concerns with making new medicines, even if everything goes perfectly, it will still be many years before this cure is available to patients. But this project is the first step in proving that it’s possible!

 

Who/what inspired you to work on EB? 

When I was a PhD student, I got to see Joanna Jacków-Malinowksa give a talk about her DEB research. I already knew that I wanted to work in DNA editing to treat human disease, and I was blown away hearing about how much DEB patients’ quality of life could be improved if DNA editing technology made it to the clinic. I immediately emailed her and asked if she would hire me as a researcher once I’d graduated. We wrote a project proposal together, and DEBRA UK granted us the funds to carry out this project.

 

What does the funding from DEBRA UK  mean to you?

I believe that DNA editing represents the future of medicine. It would allow doctors to correct the underlying causes of genetic diseases like DEB rather than just treating symptoms. The funding from DEBRA UK will allow us to take cutting-edge DNA editing technologies and apply them to cutting-edge models (like 3D skin constructs made from real patients’ cells). By combining the latest technology from both fields, we’ll have the best chance at laying the groundwork for a new DEB treatment.

 

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

As a “wet lab” researcher, most of my time is spent in the laboratory. Once this new project is fully underway, the first step is to create the custom tools I need to edit patients’ DNA using molecular biology techniques. Then, I’ll “transfect” (i.e. insert) these tools into patient cells grown in dishes. After the tools have gotten to work, I’ll take the DNA out of the patient cells and check to see if the edits have been made. If they have, I’ll take the edited cells and see what difference the edits have made in the cells’ ability to make the protein glue.

This all involves a lot of fancy equipment like confocal microscopes and cell sorting machines. I’ll even have the opportunity to learn new techniques that I’ve never used before, which is very exciting!

 

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

Our team consists of three PhD students, a masters student, a research technician, and a postdoc (me!). The students are all working on slightly different projects, but all with the main goal of either treating or better understanding DEB. Also, each person’s work supports the others’ in some way. For example, one PhD student is using a specific kind of DNA editing technology, while another 
student examines the unwanted “off-target” effects of that technology. The research technician is working on developing a 3D skin model that better represents DEB patients’ real skin, which everyone else in the lab can use for their experiments. The most important member of our team is Joanna Jacków-Malinowksa, who runs the entire lab. She guides everyone’s research by helping us interpret our results and make plans for future experiments based on what we’ve just learned.

 

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

Anytime I’m not in the lab, I like to turn off my “science brain” by doing something active or creative. I love to play volleyball, go for long walks, paint, read fiction, and play word games online with my family who live overseas.

 

What these words mean:

Transfect = process for passing genes or parts of genes into cells without using viruses

DNA editing = making changes to the genes within a cell

Confocal microscope = a microscope using lasers to more clearly visualise details within cells

Postdoc = a postdoctoral researcher – someone who has already completed a PhD research qualification and is continuing their research

“Off-target” effects = unwanted changes to DNA sequence that isn’t part of the gene being targeted by a gene editing therapy and could cause side effects

 

Full glossary of scientific terms