Epithelial Cell Biology in ENT Research (EpiCENTR) Group

The EpiCENTR group applies knowledge from developmental, stem cell biology and bioengineering approaches to generate new therapies for children with ENT disorders.

EpiCENTR brings together fundamental biologists with clinician scientists to address unmet clinical needs using stem cell and epithelial biology research methods. Our current research focus is on airway epithelial regeneration during healthy ageing, and airway disease in patients with epidermolysis bullosa.

To apply or target epithelial cells in clinical therapy, it will be critical to understand the mechanisms that regulate their behaviour, including during healthy ageing. We use human primary cell culture, including 2D and 3D organoid cultures, as well as in vivo lung injury models in mice to understand the repair of epithelial tissues.

The LAMA3, LAMB3, and LAMC2 genes encode protein subunits of a protein called laminin 332, that bridges epithelial integrins and dermal collagen fibrils. Mutations in these genes, or in COL17A1, disrupt epithelial cell anchorage and cause junctional epidermolysis bullosa (EB), a genetic disorder where patients suffer from extremely fragile surface tissues that painfully blister and scar with minimal trauma. However, JEB also presents with heterogenous airway manifestations including the loss of laminin-332 expression, and the full extent of airway involvement in EB remains unknown.

A cohort of EB patients at GOSH have been identified who suffer significant morbidity as a result of epithelial disease in the larynx and trachea. Our initial pre-clinical experiments indicate that gene-corrected epithelial stem cell transplantation may be a feasible clinical treatment for patients with airway problems associated with epidermolysis bullosa. Development of successful cell transplantation approaches in this setting would have broader consequences for airway disease management.

This work has been funded by the EB charity DEBRA and GOSH Charity. We collaborate with Dr. Anna Martinez (GOSH), Dr. Gabriela Petrof (GOSH) and Prof. John McGrath (Kings College London).

EpiCENTR brings together clinicians from Great Ormond Street Hospital for Children and scientists from UCL and is based within the Zayed Centre for Research into Rare Disease in Children, a new research facility opened in 2019.

Researchers