Speeding up drug discovery for cancer in RDEB

I’m Prerna Kadam. I recently started my PhD in Prof Gareth Inman’s group based at the Cancer Research UK Scotland Institute, University of Glasgow. I am working on a DEBRA funded project for repurposing drugs for the treatment of recessive dystrophic EB (RDEB) squamous cell carcinoma.

Which aspect of EB are you most interested in?

The most severe forms of recessive dystrophic epidermolysis bullosa (RDEB) result in complete loss of a protein called collagen-7. This is an important protein for skin strength as it forms fibres, called ‘anchoring fibrils’, that stick the top layer of skin cells (epidermal cells) to the layer beneath (dermis). Skin without collagen-7 is vulnerable to the two layers separating which causes blisters and wounds to form.

This skin damage results in an immune reaction called inflammation and the production of scar tissue, called fibrosis. The wounds can heal but the skin remains vulnerable because of the lack of collagen-7 and more blistering and wounds will form leading to repeated episodes of inflammation and fibrosis, and a high risk of cancer development.

My research is a drug discovery approach using repurposed drugs to treat cancer in RDEB patients. Repurposed drugs are drugs that are already approved for treating a different condition but are found to be effective for others. They can be made available to patients more quickly than completely new drugs because they have been tested for safety, and doses, side effects and methods of delivery are already established. We want to understand how RDEB skin is different from cancer in RDEB patients and how we may exploit those differences. This will assist in better treatment options. Creating therapeutic alternatives that will directly affect people with EB and could play a part in improving their quality of life excites me. One of the main motivators for my research journey has been conducting studies that have the potential to directly improve patient outcomes.

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

By the age of 55, 90% of people living with severe forms of RDEB have developed skin cancer. There are currently no approved effective targeted therapies, and cancer sadly continues to be the leading cause of death for people diagnosed with severe RDEB. For this reason, my research focuses on the most effective ways to target cancer in RDEB patients without aggravating their pre-existing skin vulnerability.

This research will enable the prompt use of drugs that have already been licensed for use in other conditions, so they can be put to use more quickly for RDEB cancer. Understanding which drugs are effective may also help us comprehend how RDEB patients’ cancer develops and how to use combination therapies to treat both RDEB and cancer. I hope my work will pave the way to better understand cancer in RDEB and provide treatment options for people living in fear of this.

Who/what inspired you to work on EB?

My research has always been driven by a curiosity for drug development and a desire to apply academic knowledge to substantial biological and therapeutic outcomes. I have worked on projects in drug development, bioinformatics (a field that merges biology, computer science and statistics), and cancer research, with a particular emphasis on understanding how treatments integrate into normal physiology.

After receiving my Master’s degree, I worked as a research technician in Dr Matthew Caley’s lab, where I first learnt about EB. Through lab meetings with Matthew, Dr Emanuel Rognoni, and Prof Edel O’Toole, I began to understand the severity of EB and the impactful work being carried out by the team. While I was applying for PhDs, Matt informed me about an upcoming opportunity in Prof Gareth Inman’s group that focused on RDEB-associated cancer drug discovery, which was exactly what I was interested in.

Gareth’s commitment, enthusiasm, and strong personal bond with EB research were incredibly motivating. For me, going to the DEBRA parliamentary reception with him was an unforgettable experience. Hearing directly from people with EB and their families highlighted the condition’s real-world effects and reinforced the responsibility researchers carry. It inspired me to approach my work with even greater diligence, integrity, and awareness, aiming to do effective and unbiased research that can truly make a difference.

Matthew, Gareth, and the powerful experiences at the DEBRA event have all been instrumental in encouraging my dedication to EB research.

What does the funding from DEBRA UK mean to you?

As an international student, I would not have been able to pursue a PhD without the help of DEBRA funding. This assistance helps me to focus on my desired research project without worrying about finances. Additionally, funding makes it possible to conduct desired experiments that are appropriate for answering relevant questions.

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

As a first-year PhD student, most days begin with planning experiments across both wet-lab and computational work. On some days, I spend all my time in the lab, while on others, I sit at my desk and use computers to analyse data and integrate experiment results. Reading and staying current with the most recent findings in the field also take up a large portion of my time.

I enjoy turning my ideas and understanding of RDEB into illustrations, which allows me to think imaginatively about the science and express complex topics more simply. Along with research, I attend meetings, present my work and get trained on new skills.

During breaks, I frequently catch up with students and colleagues from various lab groups or go for a coffee, which provides a wonderful balance to my day.

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

I feel incredibly fortunate to be part of a collaborative and supportive research community. My PhD supervisors, Prof Gareth Inman, Prof Karen Blyth, and Dr Kirsteen Campbell, are experts in cancer biology, model generation, and therapeutic discovery, and their assistance has been invaluable. Models of EB are vital so that experiments can be carried out without risks to people living with EB when potential treatments are at an earlier stage of development, and to better understand how they might be working.

Dr John Pritchard, a postdoctoral researcher in our lab, works closely with DEBRA to generate RDEB models and has led the major screening effort for this study. He has been a fantastic source of support, always friendly and encouraging. Dr Max Bone and Dr Samantha Campbell are the backbone of our bioinformatics assistance, who have been a helping hand in my effort to integrate computational work and wet lab experiments to give a holistic perspective to my research.

Other lab members, including Dr Michela Raponi, and Dr Christina Schoenherr, as well as other PhD students Rhona Hurley, Lucy Li, and Matthijs van Wijngaarden, have also been extremely helpful, providing ideas, optimism, and a constant willingness to help. Being part of such a team has made my PhD experience both gratifying and motivating.

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

Outside of the lab, I am frequently found experimenting in the kitchen and cooking a variety of meals. I love spending time in nature and exploring museums, so I try to plan walks, hikes, and museum trips whenever feasible. These activities give me a sense of calm and help me recharge mentally.

I also treasure my time with family and friends. As an international student with a family in India, I make the most of every visit home by eating wonderful food, spending quality time with my family, and celebrating festivals together. These moments allow me to refresh and stay connected, despite the distance.