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Prof John F. Marshall
Institution(s): Barts Cancer Institute, Queen Mary University of London
Research focus: Cancer migration and spread
What are your own areas of research, and what insights do these give you on EB?
I study a group of molecuyles on the surfce of cancer cells that enable them to grow faster, move, invade and potentially spread to another part oft he body. These molecules are called integrins, so called because the integrate the inside of the cell with the outside of the cell, providing information to the cell about where they are, and what they should do next: divide? move to another site? produce enzymes and invade?
My research focusses first on understanding how these integrins are able to perform these multiple different activities and secondly on developing drugs that can stop them from doing these activities that help cancers to grow and spread. The integrin that excites me most is called alpha-v beta-6 (written avb6). This integrin is not on the surface of most normal cells but appears in high levels of the squamous cancers of EB patients, representing a target for therapy. In addition avb6 appears on the skin cells in EB blisters. This I hope will develop into a gene therapy to deliver the missing collagen 7 directly into those cells that have avb6 on their surface.
Where do you see the biggest contributions research can make to improving options for people with EB?
I read with fascination and admiration the many different strategies colleagues in the EB field have made in the last 20 years that will see great developments in the coming decades. When I joined this EB research community, the amount of deep biological understanding of the disease was largely absent. In addition, if one had an idea for a therapy, or for a deeper understanding of the biological processes that cause and maintain the disease, there was no system that allowed you to test out your idea, before trying it of those with EB. This situation has transformed. We now have brilliant scientists who have created mouse models of EB that allow you to investigate the disease AND test novel therapies. Other researchers have concentrated on understanding the genetic principles that lead to the formation of cancers, the reason why many EB patients die so early. And yet other scientists have concentrated on developing different ways to introduce the corrected genes into the tissues of those with EB in order that their tissues will start to work correctly. Each of these developments are getting closer to generating valuable treatments for those with EB.
What are the current most urgent research questions, both in basic knowledge and translational research?
1.We must understand fully the biological processes that create the environment for generating cancers. Much of this information is being gathered now, but we have to develop drugs/therapies that can interrupt and stop these cancer-promoting processes
2.Once cancers have developed we need better targeted therapies that can selectively kill the cancer cells. Such therapies need to be able to be given in the blood so that all the cancer cells can be reached and killed. This is a very big and difficult question to address, but I dont think impossible.
DEBRA and EB-ResNet members are grateful for your dedication to helping people with EB; what do you find rewarding about being a member of MSAP?
The inspiration for remaining an active member oft he EB community are those with EB and their families that I have had the privilege to see and meet. While the biology oft he disease is extremely fascinating for a cancer research scientist like me, meeting and being with those with EB, listening to the stories of their lives, anchors you to how important this disease is. I wish to remain an active researcher in this field for all my career. I now have the very great honour of co-chairing the MSAP committee that reviews all the research ideas submitted to DEBRA and where possible fund their research, a huge privilege. It also means I get to meet regularly with MSAP colleagues, who are some of the most inspirational scientists in the world, in any diesease, and to learn from them. It is a huge pleasure to be part of DEBRA and to try to help this reseafch community grow.