Interrogating the cellular and molecular mechanisms of tissue fibrosis

Fibrosis is a pathological process where excessive extracellular matrix deposition leads to scarring and loss of tissue function, contributing to progressive organ failure. It is a hallmark of chronic diseases affecting the lungs, liver, and kidneys. This project will investigate the cellular and molecular mechanisms underlying pericyte differentiation, a key event in fibrosis development.
Pericytes are vascular-associated mesenchymal progenitor cells with multipotent potential, sharing similarities with bone marrow-derived mesenchymal stem cells (MSCs). While MSCs are well-characterised, pericytes may exhibit distinct responses to inflammatory cues. Notably, the inflammatory marker TNF-alpha enhances osteogenesis in MSCs, yet how pericytes interpret pro-inflammatory and pro-fibrotic signals-such as TGF-beta, IL-1beta, and TNF-alpha-is poorly understood. Clarifying these responses is essential to understanding fibrosis initiation.
The project will initially employ 2D in vitro human pericyte cultures exposed to defined inflammatory environments. Differentiation into adipogenic, chondrogenic, and osteogenic lineages will be assessed using commercial kits, alongside expression profiling via qPCR arrays. The transition to myofibroblasts will be tracked through fibrotic marker expression and phenotypic changes.
To validate in vitro findings, in vivo experiments will be conducted using a mouse model of fibrosis. This will enable the assessment of pericyte behaviour in a physiologically relevant context, including their response to chronic inflammation and their contribution to fibrotic lesion formation.
This will provide expertise in advanced cell culture, molecular biology, qPCR, bioinformatics, and in vivo experimentation. A placement with Stemcell Technologies will allow participation in product development related to pericyte and stem cell biology and gain exposure to proprietary platforms.