Speaker: Prof Tim Johnson, Director, Immunology Therapeutic Area, UCB Pharma, Slough & Professor of Kidney Science, University of Sheffield, Sheffield
Tissue Scarring – Its all in the Glue!
Tissue scarring and fibrosis is the largest clinical unmet need in the developed world, being directly responsible for 45% of all deaths. It affects every organ in the body, typically occurring as a consequence of some underlying chronic condition (such as diabetes or hypertension), or by exposure to environmental triggers (such as atmospheric pollutants or enviromental toxins). It is characterised by excessive accumulation of extracellular matrix proteins, fibrogenesis and remodelling of the target organ that leads to functional loss.
There are several major players in the fibrosis pathway, but Transglutaminase 2 (TG2) appears to be a key mechanism in disease progression. TG2 is a powerful protein crosslinking enzyme that can accelerate collagen deposition, render this collagen resistant to proteolytic decay and further recruit TGFb1 to the area of disease. The seminar will describe TG2, its mechanism in fibrotic remodelling and examine ways to therapeutically block its pro-fibrotic transamidation activity.