H.R.D. (Henry) Showell, MSc
PhD Student
E-mail:
h.r.d.showell rug.nl
Field/Discipline
Expertise
Functional interactions between WNT/β-catenin signalling and the pro-fibrotic lung microenvironment. Idiopathic Pulmonary Fibrosis (IPF) is a devastating and fatal lung disease, characterised by excessive fibrosis, destruction of alveolar structures, and progressive loss of lung function. At its core, IPF involves aberrant epithelial-mesenchymal crosstalk, myofibroblast activation, and extensive extracellular matrix deposition; processes strongly influenced by dysregulation of WNT signalling pathways. Traditional research methods, such as bulk tissue analysis or oversimplified cell culture systems, often fail to capture the spatial complexity and cell-cell interactions underpinning fibrosis progression. This limitation is particularly significant in IPF, where WNT signalling pathways vary widely between epithelial and stromal compartments and are subject to dynamic regulation within the pro-fibrotic microenvironment. My research addresses this gap via the use of advanced experimental systems such as lung organoids derived from primary epithelial cells and precision-cut lung slices (PCLS), to model the fibrotic microenvironment. These models enable spatial and temporal analysis of WNT/β-catenin signalling, providing insights into how pro-fibrotic cues disrupt epithelial repair mechanisms and drive pathological fibroblast activation. Specifically, I aim to identify how targeted modulation of WNT signalling can reverse fibrosis and restore tissue homeostasis. This involves exploring the therapeutic potential of combining WNT modulators, such as porcupine inhibitors, with existing and emerging anti-fibrotics such as nintedanib and nerandomilast. By bridging the gap between in vitro findings and translational outcomes, this research attempts to deliver novel therapeutic strategies that improve treatment efficacy and ultimately benefit IPF patients.
| Last modified: | 11 November 2024 9.58 p.m. |