Projects
Mayo Clinic's Genomic and Exposomic Hepatobiology Lab studies the genetic epidemiology and pathogenic mechanisms of the cholestatic liver diseases primary biliary cholangitis and primary sclerosing cholangitis. Current research projects related to these diseases focus on:
- Genomics. This long, ongoing study continues to dissect the genetic predisposition to primary biliary cholangitis and primary sclerosing cholangitis using array- and sequencing-based genotyping methodologies. This project has already identified numerous genes that potentially contribute to the development of primary biliary cholangitis and primary sclerosing cholangitis, as well as drugs that might be good candidates to treat these diseases. Future findings will continue to provide novel insights into primary biliary cholangitis and primary sclerosing cholangitis.
- The exposome and metabolome. This study seeks to determine whether environmental exposures and downstream impacts on metabolic processes contribute to disease pathogenesis in primary biliary cholangitis and primary sclerosing cholangitis. The lab's team uses cutting-edge, ultrahigh-resolution mass spectroscopy platforms. The findings of this study will provide a new appreciation of similarities and differences in disease pathogenesis in primary biliary cholangitis and primary sclerosing cholangitis.
- Peripheral immunity. This study aims to describe immune alterations in patients with primary biliary cholangitis or primary sclerosing cholangitis by evaluating peripheral immune cell type composition — the immunome — using mass cytometry. The study also evaluates activation state — methylome, transcriptome and proteome — using sequencing and proximity extension-based methods. Individual and combinatorial approaches to analyzing the resulting data will provide valuable insight regarding immune mechanisms contributing to these diseases.
- Gut microbial composition and dynamics. This study aims to characterize disease-associated differences in the gut microbial dynamics of patients with primary biliary cholangitis and primary sclerosing cholangitis. Next-generation sequencing of stool bacteria and fungi coupled with ultrahigh-resolution mass spectroscopy are used to gather data to evaluate the stool exposome and microbiome. This study will provide new insights into the link between gut health and the inflammatory nature of these diseases.
- Community resources. These resources serve to coordinate and disseminate data generated by our large-scale, omics-based experiments, along with residual biospecimens, to collaborators within the greater primary biliary cholangitis and primary sclerosing cholangitis scientific community. The availability of these resources helps quicken the pace of cholestatic disease research and facilitates the pursuit of complex multi-omics analyses using artificial intelligence and machine-learning approaches.