Research Projects

Biliary atresia (BA) is a lethal and one of the most common neonatal cholestatic liver diseases. The disorder soon after birth leads to progressive destruction of bile ducts followed by damage to the liver leading to fibrosis, cirrhosis, and eventually liver failure, if untreated. The etiology of BA remains poorly understood, with multiple etiological factors (genetic, immunological, infection, environmental) studied and proposed. However, the genetic basis of BA is underexplored, as most past studies have focused on common variants in small cohorts or single selected genes. Hence, there is limited knowledge about rare, potentially deleterious variants that may influence hepatobiliary development, inflammation, or ciliopathy-related pathways. Understanding the role of these variants could provide insights into BA pathogenesis and identify potential therapeutic targets. With the latest advancement in genomics in the form of availability of different sequencing methods it is now possible to do detailed genetic analysis in various diseases. Being a mysterious life-threatening disorder, it is important to take advantage of the latest technology and reinvestigate the associated genetic defects and their roles at a larger scale to better understand the disease pathogenesis and improve the disease outcome. To the best of my knowledge so far, no attempt similar to this proposal on BA has been made or reported. This project introduces a combination of whole exome sequencing and functional studies to identify novel and rare genetic variants associated with BA. Unlike earlier studies relying solely on GWAS, this approach integrates high-resolution sequencing with cellular assays to validate and elucidate the impact of identified variants. Integrating bioinformatics with experimental studies will significantly advance previous efforts and provide a comprehensive understanding of the genetic and molecular mechanisms underlying BA.