Entries by awp-admin

Early work on structural role of ECM proteoglycans

My early work defined lumican, a keratan sulfate proteoglycan of connective tissue ECMs of the cornea, tendon, skin, cartilage. These studies predate completion of the Human Genome Project, necessitating the purification of the lumican protein, establishing its N-terminal amino acid sequence, isolating genomic and cDNA clones and Sanger sequencing of the lumican gene. Subsequently, we generated gene-targeted lumican-deficient mice that developed cloudy cornea, and skin and tendon fragility due to abnormal collagen fibril structure (Chakravarti, 1998).

 Emerging role of ECM components in immune response and inflammation

Beyond tissue structure, we discovered that collagen-free lumican has a second role in modulating inflammation and immune response (Wu, 2007; Shao2013). Other related members of this proteoglycan family also have dual roles in tissue structure and cell signaling. Lumican interacts with cell surface proteins (integrins, caveolin-1 and CD14) on neutrophils, macrophages, and dendritic cells to promote toll-like receptor (TLR)-4 mediated innate inflammatory signals and defense against bacterial infections.

Human corneal organoids

We are exploring the use of human corneal organoids as a pre-animal model system to investigate human corneal development and disease. Matured for up to 4 months in culture, these human corneal organoids establish a layered ECM-rich cornea-like tissue (Foster, 2017). Single cell transcriptomic studies show all major corneal cell types (Maiti, 2022) and a cornea-like stromal extracellular matrix of collagens and proteoglycans (Ashworth, 2025).

Sean Ashworth, PhD Joins the Lab

June 13, 2022 Sean Ashworth, PhD from the School of Optometry and Vision Sciences, Cardiff University is joining the lab in September this year. Welcome Sean!

Extracellular matrix in the healthy cornea

A major focus in our laboratory is understanding the structure and functions of the cells and the ECM of the cornea. The transparent cornea provides two thirds of the refractive power of the eye and serves as a protective barrier through unique adaptations of the cells and the ECM. The stromal ECM connective tissue is a highly organized array of collagen fibrils and regulatory proteoglycans produced by a specialized fibroblast, the keratocytes. We are trying to understand properties of keratocytes, their development and whether they can be maintained in culture to produce a cornea-like stromal ECM.