Research into Kindler Syndrome and the development of skin cancer

Professor Valerie Brunton works in Edinburgh, UK, on a rare type of epidermolysis bullosa (EB) called Kindler syndrome. This is caused by genetic changes that mean the Kindlin-1 protein doesn’t work properly. Patients suffering with this form of EB have thin skin that blisters and sunburns easily and an increased risk of skin cancer (squamous cell carcinoma). This work uses a family of mice without Kindlin-1 protein to study how the growth and spread of skin cancer is related to Kindlin-1 protein. 


Grant Title: Understanding the role of Kindlin-1 loss in the development of squamous cell carcinoma

Investigators: Professor Valerie Brunton, Chair of Cancer Therapeutics, University of Edinburgh

Co-investigators: Dr Adam Byron (biochemistry) University of Edinburgh,

Professor Albena Dinkova-Kostova (cellular medicine) University of Dundee, and

Collaborator: Dr Alan Serrels (cancer / tumour microenvironment) University of Edinburgh

Institution: University of Edinburgh

Start Date: 1st October 2020

Grant amount: £230,271.67 over 3 Years (Proposed 49% funding with DEBRA Austria)

Research type: Laboratory/Pre-clinical


Kindler syndrome (KS) is a rare skin disorder that develops early in life. People with KS have skin blistering, and develop thin or papery skin. They are also highly sensitive to ultraviolet (UV) radiation from the sun and sunburn easily. KS also increases the risk of developing a type of skin cancer called squamous cell carcinoma. KS occurs due to a genetic mutation in the FERMT1 gene. Mutations in FERMT1 results in the production of a defective protein called Kindlin-1.

Currently there is very little known about why the loss of a functional Kindlin-1 protein in the skin of people with KS increases their risk of developing squamous cell carcinoma (SCC). The group have previously carried out experiments on skin cells grown in the laboratory which has shown that loss of Kindlin-1 sensitises cells to UV radiation. To understand why this happens they will use a mouse model which mimics sun exposure to UV radiation. Using mice in which they can delete the Kindlin-1 protein from the skin, it will help identify UV induced changes that are specifically controlled by loss of Kindlin. The next stage will look at whether loss of Kindlin-1 in the skin leads to increased skin cancer formation following UV exposure.

The 3 aims of this project are:

Aim 1: Do changes in the tissue environment of tumours lacking Kindlin-1 contribute to their growth and metastatic spread?

Aim 2: Do Kindlin-1 binding partners (molecules that interact), regulate cancer (SCC) growth?

Aim 3: Does the loss of Kindlin-1 promote UV-induced skin cancer (SCC) formation?

DEBRA UK previously funded Professor Valerie Brunton at the University of Edinburgh towards research in Kindler Syndrome. To read more about this earlier, completed project.

About this research and why it is important

"Our research has uncovered important changes in the tumour microenvironment (the normal cells and molecules that surround and support the growth of tumour cells), that are controlled by Kindlin-1. By studying these changes, we hope to gain a better understanding of how we can prevent the development and progression of skin cancer in patients with Kindler syndrome." Professor Valerie Brunton 

Investigator Biography:

Professor Valerie Brunton

Professor Valerie Brunton

Professor Valerie Brunton is Chair of Cancer Therapeutics at the University of Edinburgh. Her interests are in understanding the biology of Kindler Syndrome associated with skin atrophy (weakening), photosensitivity, and an increased risk of developing cutaneous squamous cell cancer. Her research aims to identify the key molecular pathways that underlie the pathology of Kindler Syndrome to help identify ways in which to treat this.