Krupa R. Mysore, MD, MS

Biliary Atresia Fund for the Cure Pilot Research Award
$50,000 over one year

Baylor College of Medicine

Molecular mechanisms of immune dysfunction in biliary atresia

For children with cirrhosis due to biliary atresia (BA), liver transplantation (LT) is a lifesaving procedure. Unfortunately, children awaiting LT develop significant number of serious infections leading to frequent hospitalizations and even death. Immune cells (white blood cells) help fight infections and are particularly important in children due to a developing immune system. Our research recently showed that certain immune cells in blood do not function well in children with BA. Liver plays a central role in the immune system, and immune dysregulation in cirrhosis is a critical area of research. The goal of this proposal is to understand the mechanisms of immune dysfunction in BA cirrhosis. Our proposal asks: (1) Can we identify unique immune gene signatures in cirrhotic BA compared to controls, (2) Can we identify associations between liver immune gene alterations and systemic (in the blood circulation) immune dysfunction in BA cirrhosis. We will study white blood cells obtained from children pre-LT to measure immune function. We will study gene changes in the liver tissue using a new technique called spatial transcriptomics. We expect to identify novel immune defects that lead to infections in children with BA, which will help develop future targeted therapies.