Dr. Daniel Johnston

This project seeks to explore the cause of the devasting skin condition hidradenitis suppurativa (HS). People with HS suffer recurring inflamed lesions in areas where skin touches skin, such as under the arms or the groin, causing great unseen pain and wounds with embarrassing odorous discharge causing social reclusion and mental health difficulties. HS disproportionally affects people with lower socioeconomic status, and it has the added affect of further driving people with the condition into further poverty through missed workdays through physical and mental illness. This disease has a great unmet clinical and social need and is an ideal starting point for our new laboratory, which seeks to perform excellent science that benefits society locally and globally in an inclusive and environmentally sustainable way. Biologically, HS is thought to originate in hair follicles " critical skin appendages with many roles in regulating bodily function. Hair follicles in HS appear to become blocked, and then rupture triggering the immune system to cause sustained inflammation and scarring. However, the chain of events is poorly understood despite consensus that hair follicles are the site of disease origin. In this work, we seek to understand how hair follicles in people with HS become so badly disrupted, and whether this information can be used to design a tissue culture model of HS hair follicle breakdown to better understand the disease, and trial potential disease treatments as a first step towards clinical use. To do this, we will take advantage of several collaborations established in recent years to gain access to cutting edge `omics data and rare tissue samples to build a picture of hair follicle vulnerability and model it in a laboratory setting. Firstly, using hair follicle biopsies, the student will be trained in their culture in the lab and learn to employ an existing model of hair follicle disruption used to study alopecia areata. The student will then undertake a systematic review of the HS literature and a computational biology analysis integrating data from collaborators to compare follicles from HS to other skin diseases. In the third aim of the project, we bring together data from our tissue culture model and `omics analysis, with data from the HS literature, with the aim of identifying factors that can cause hair follicle collapse, and determining if hair follicles from HS patients are more vulnerable to stresses. We will seek to reverse any disruption using pharmacological treatment which may inform future HS treatment strategies.

My research group seeks to model the initiating events in the pathogenesis of the devastating inflammatory skin disease hidradenitis suppurativa using ex vivo hair follicle culture and integrating data from existing single-cell transcriptomic datasets. However, these datasets are limited as the inclusion of the key follicular unit is inconsistent across samples. In this project, we will build a transcriptomic map of hidradenitis suppurativa (HS) hair-follicle vulnerability, by precisely taking multiple hair follicle samples from axillar resections and performing bulk and single-RNAseq from multiple samples/patient. The single-cell cell samples will identify cells types in the deconvoluted bulk RNAseq, increasing the power of the dataset. This proposal seeks to logically extend the scope of a current TRDA PhD project and greatly enhance its impact. Rather than relying on limited publicly available data, this proposal will allow the creation of a bespoke dataset which will benefit both our immediate and future research questions and the wider field. In addition, we seek to hold an ambitious and inclusive PPI event for HS patients in conjunction with partners in HS Ireland. Adapting the current best-in-class model developed by key opinion leaders in Denmark, this event will be the first of its kind in Ireland.

The research focusses on aim is to advancing our understanding of cell interactions driving disease processes in the gut, joint and skin, to develop new therapeutic approaches for immune-mediated inflammatory diseases including rheumatoid arthritis (RA), inflammatory bowel disease (IBD) and Hidradenitis suppurativa (HS).