Interrogating mechanical signals in liver fibrosis for anti-fibrotic therapy
Liver disease is increasing and a major cause of morbidity and mortality. Long term damage to the liver results in scarring, known as liver fibrosis, which impairs liver function. Treatment of liver fibrosis is transplantation. Unfortunately this is limited due to the high numbers of people in need of a transplant. For this reason, identifying effective anti-fibrotic treatments for the disease would be hugely beneficial, as none currently exist. The characteristic scar promotes progression of fibrosis. Discovering how to block scar production or how it signals to surrounding cells that perpetuates fibrosis may lead to new drugs to treat liver disease.
The scar is sensed through receptors on the surface of cells, known as integrins made up of an alpha and beta subunit. Dr Su's supervisor’s group has shown that activation via integrins is one of the key steps in activation of scar producing cells, with key leads that the integrin subunits, alpha11 and beta1 play central roles. This is an exciting opportunity paving the way for me to discover how the integrins signal inside cells to induce changes leading to excessive scar production. This information is anticipated to lead to new drugs compounds capable of blocking integrin signalling on the outside and/or within the cell to prevent and/or reverse liver fibrosis.
Dr Su's MRC Clinical Fellowship is within the lab of Dr Piper-Hanley at the University of Manchester. Her pharmaceutical collaboration is with Roche Genentech. She will study mechanosignalling cues that promote fibrogenesis in the diseased liver, and how mechanosignalling cues mediated by the extracellular matrix interacts with immune components in fibrogenesis.