My research interest is hepatic epithelial cell function and dysfunction. My focus is principally on cholangiocytes (epithelial cells that line intrahepatic bile ducts) because of their biologic and clinical importance, new hypotheses and techniques developed for their study, and advancing cholangiocyte pathobiology - an underserved area of research.
The main studies of my research include:
- The cholangiociliopathies, a group of incurable genetic diseases manifesting biliary cysts with or without fibrosis; autosomal recessive and autosomal dominant polycystic kidney disease (ARPKD and ADPKD).
In this area, I am focused on the central hypothesis that normal sensory/transducing activities of cholangiocyte cilia are disrupted in cystic liver disease leading to altered intracellular signaling and modified miRNA expression resulting in cholangiocyte hyperproliferation, ductal dysmorphogenesis and hepatic cyst formation.
- The interactions between cholangiocytes and Cryptosporidium parvum (C. parvum), an emerging pathogen causing intestinal and biliary cryptosporidiosis.
In this area, I focus on the central hypothesis that C. parvum-cholangiocyte interactions activate host-cell TLR/NF-kB signaling cascades initiating cholangiocyte defense responses including upregulation of both TLRs and antimicrobial peptides (defensins) through both transcriptional and post-transcriptional (endogenous miRNA-mediated) gene regulation.
For more information, please visit my lab site.