By Marija Dimitrievska

Hello, my name is Marija Dimitrievska and I am a PhD student in Prof McGrath’s Genetic Skin Disease Group at St. John’s Institute of Dermatology, King’s College London.

  

Which aspect of EB are you most interested in?

I am particularly interested in understanding the changes inside cells that affect wound healing and skin cancer development in recessive dystrophic epidermolysis bullosa (RDEB). I am working on a new method for cancer detection at an earlier stage before the cancerous changes become visible. I am excited about the development of new techniques that can improve the care doctors provide with the prospect of improving patient outcomes.

 

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

My project aims to improve clinical care for people living with RDEB by developing a new, non-invasive, way of detecting cancer at the early stages. ‘Non-invasive’ means that no instruments are put into the body or through the skin. Non-invasive procedures, like scans, are more tolerable for patients than biopsies that may involve creating a wound to remove a skin sample. Some people with RDEB develop skin cancers throughout their lives which can have a severe impact on health. The cancers tend to appear at sites of chronic (non-healing) wounds, which are highly inflamed, painful and have scarring. These things make it difficult to identify a skin cancer just by looking, especially at an early stage. This difficulty results in multiple biopsies being taken from sites of suspicion for diagnosis; however, this is a highly invasive procedure, and often there is no cancer present.

To tackle this problem, I am using Raman spectroscopy, a technique that involves shining light on the skin and measuring the ‘light scattering’. Light scattering involves lots of different behaviours of light; not just reflecting from shiny surfaces or refracting, which is the bending of light that we can see when it goes through glass or water.

Some molecules may absorb some frequencies (colours) of light and/or emit others. Every molecule has a specific ‘fingerprint’ of light scattering; therefore, I can detect with very high sensitivity and accuracy the molecular changes occurring in RDEB skin when cancer is present. So far, my work has involved imaging non-cancerous and cancerous RDEB biopsy samples to identify the ‘signature’ changes associated with the cancer. I am now moving on to using a fibre-optic Raman handheld probe that can detect these signature changes, with the goal of creating a bedside test that can help clinicians to monitor suspicious parts of chronic wounds and improve decision making about which part to biopsy.

Another aspect of my work uses nanoneedles, which under a powerful microscope would look like a ‘bed of nails’. They are capable of collecting samples from individual cells in the skin and also delivering molecules into the skin. By applying them as a patch on the skin for sampling, I hope to be able to take a non-invasive ‘nano-biopsy’ of the molecules such as proteins and fats that are in the skin. This would provide information as to whether cancer is likely and if a further skin biopsy is necessary. This can have a great impact as a non-invasive bedside test, helping reduce the number of biopsies needed.

I am also using nanoneedles to deliver a gene therapy into RDEB patient cells and correct the changes that cause the fragile skin. My hope for the future is that this can be applied in people with EB using nanoneedles built onto wound dressings as a form of treatment.

 

Who/what inspired you to work on EB?

My journey into EB research began during my Master’s course at St. John’s Institute of Dermatology, where I worked on using base editing, a type of gene editing, which functions as an eraser and pencil to precisely correct genetic changes responsible for causing dominantly inherited DEB (DDEB). DDEB is caused by only one genetic change in a pair of genes, while RDEB happens when both genes in the pair have a genetic mistake. During this period, I got the opportunity to learn more about recessive inherited DEB (RDEB), as well as the use of nanoneedles for delivering a gene therapy safely into patient cells.

My interest in translational research (converting lab results into treatments) and the direct impact it can have on patient care led me to my PhD. I am driven to help transform laboratory discoveries into practical tools and treatments that can be used in the clinic, especially in the realm of cancer detection for EB. By enabling earlier detection of cancer, my work has the potential to significantly improve the quality and length of life for people with RDEB, embodying my ambition to contribute to meaningful advancements in medical practice.

 

What does the funding from DEBRA UK mean to you?

The funding from DEBRA UK is incredibly valuable to me and my supervisors. It gives us the resources to pursue our research, testing our hypotheses while working in a highly skilled multidisciplinary team. This support allows us to focus on making real-world impacts, bringing our findings from the lab to the bedside where they can make a real difference for those living with EB.

 

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

Earlier on, much of my time was in the lab, growing patient cells, studying and attempting to correct a genetic change causing RDEB and preparing skin sections for Raman microscopy. Recently, I have been spending my time writing programming code to process my Raman results. So, the reality is my days can vary a lot, and can see me doing lab work or data analysis. Beyond this, my work in the lab sees me collaborating with a large range of people across different projects, and I also help mentor students who are undertaking short-term placements with us.

 

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

My project thrives on the collaborative energy from three distinct labs, blending a wide range of specialties into a cohesive, multidisciplinary team. This setup allows me to leverage the extensive experience and diverse expertise of team members, applying their knowledge in innovative ways to my EB research. The cross-specialty insights we gain are invaluable, often bringing new perspectives to our work. Central to the team is Prof John McGrath, whose guidance is instrumental. His experience not only steers the project but also fosters an environment where learning and development are at the forefront. Moreover, guidance from Dr Ciro Chiappini regarding nanoneedle use and discussions with Dr Mads Bergholt about our Raman findings are crucial to driving the project forward.

 

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

Taking care of my plants is a peaceful hobby that helps me unwind. I enjoy skincare and approach my skincare routine with the same curiosity I have in the lab, applying a bit of my research mindset to figure out the best products and ingredients to optimise my routine. Roaming around London offers endless opportunities to discover something new, and I seize every chance to travel, as I’m a big sightseer. These activities offer a refreshing counterbalance to my research, grounding me in the simple joys of life.

 

What these words mean:

Non-invasive = no instruments are put into the body or through the skin.

Biopsy = surgery to remove a small amount of skin (or other tissue).

Nano = one billionth (or something very, very small).

Spectroscopy = observing how light is absorbed and emitted.

Fibre-optic = using flexible glass or plastic 'optical fibres’ that light can travel along.

 

Full glossary of scientific terms