The RAS and AGE Laboratory

Head: Dr Chandana Herath
Our group has played a leading role in establishing that angiotensin II (Ang II), the key effector peptide of the RAS, plays a central role in the pathogenesis of hepatic fibrosis and its complications. This work has stimulated major interest in the potential therapeutic role of RAS blockade in liver disease. In addition to establishing the central role of Ang II, we have shown that there is an alternate, angiotensin converting enzyme 2 (ACE2) dependent arm of the RAS which is activated in both experimental and human chronic liver disease and opposes many of the vasoconstrictive and profibrotic effects of Ang II. Our studies explore the therapeutic role of manipulation of the RAS in experimental liver disease and portal hypertension, including the potential role of treatments targeting the alternate, ACE2 dependent pathway.

AGEs are a group of chemically heterogeneous compounds found in large amounts in the western diet and which are also produced endogenously in diabetes. They are formed by non-enzymatic reaction between plasma proteins and reducing sugar. We have shown that these compounds can worsen experimental liver injury. Our current experiments are focused on establishing whether manipulating the levels of AGEs in the diet or blocking AGE receptors can be used to reduce liver damage in experimental fatty liver disease and diabetes.

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Liver Immunology Laboratory

Head: Dr Adam Testro
Bacterial infections are common in patients with cirrhosis and are a major cause of mortality. The majority were due to spontaneous bacterial peritonitis (SBP). Bacterial translocation, the passage of bacteria from the intestinal lumen to regional lymph nodes, in addition to impaired host defences, are thought to be the major contributing factors predisposing to Gram-negative bacterial infection in patients with cirrhosis. The innate immune system, and in particular the Toll-like receptor (TLR) family, play a central role in the defence against bacteria and in the systemic response to endotoxemia. The major focus of this laboratory is to investigate the role of TLRs in cirrhosis and to formulate therapies targeting these receptors, particularly, TLR2 and 4.

These immune defects found in patients with end-stage liver disease can also influence the likelihood of post-liver transplant allograft rejection. Our laboratory also has an interest in immune monitoring post-liver transplant with regards to the interplay between the innate immune response, anti-rejection medication and organ rejection.