Awarded a two-year, £144,581 grant from Pachyonychia Congenita Project.
Several genetic skin conditions specifically affect the skin found on our palms and soles (palmoplantar), including the palmoplantar keratodermas (PPKs). PPKs are characterised by a thickening of palmoplantar skin, which is often accompanied by pain when walking, as in pachyonychia congenita. The skin forms a vital barrier between the human body and the environment and palmoplantar skin is uniquely adapted to provide this barrier function whilst withstanding high levels of mechanical stress. Compared to hairy skin covering the rest of the human body, it is thicker, hairless and has a distinctive gene expression pattern. Many of the genes mutated in inherited PPKs are only significantly expressed in palmoplantar skin, and yet this specialised skin is relatively understudied and the biological differences in palmoplantar skin are not well understood. Consequently, current PPK disease models grown in the lab based on skin cells derived from body skin, are not ideal or necessarily relevant for studying PPKs. To bridge this knowledge gap we are growing and studying skin cells in the lab that were extracted from human palm skin. However, it is not currently possible to confirm that these cells are a good model for palm skin due to the lack of published data on palmoplantar skin. We propose that a detailed comparison of gene expression differences between human palm and body skin from the same individuals will provide a robust data set to establish key differences that define palmoplantar skin. This information will then be used to assess how the palm skin cells perform as a model of palm skin in the lab. In addition, by using gene editing technology to introduce a mutation found in some pachyonychia congenita patients, we will compare how the mutant palm cells behave as a disease model compared to body skin cells.
Project Title: Towards an in vitro model for studying Pachyonychia Congenita
Principal Investigator (PI) Name: Diana Blaydon, PhD
PI Affiliations: Queen Mary University of London
