Identifying genetic and exposomic predispositions in cholestatic disorders
The Genomic and Exposomic Hepatobiology Lab at Mayo Clinic is applying genomic and exposomic approaches to better understand the pathogenesis of chronic cholestatic liver diseases. This step is critical to devising new, effective treatments.
Overview
The aim of Mayo Clinic's Genomic and Exposomic Hepatobiology Laboratory led by Konstantinos N. Lazaridis, M.D., is to investigate the genetic and environmental predisposition and downstream impacts of biological processes that contribute to the development and progression of the chronic cholestatic liver diseases primary biliary cholangitis and primary sclerosing cholangitis.
Primary biliary cholangitis and primary sclerosing cholangitis are rare chronic and progressive cholestatic liver diseases that contribute to hepatic failure and shorten patient life expectancy. Immune-mediated damage of cholangiocytes — the epithelial cells that line the bile ducts — likely cause primary biliary cholangitis and primary sclerosing cholangitis.
Genetic and environmental factors are strongly suspected to significantly contribute to the etiologies and outcomes of primary biliary cholangitis and primary sclerosing cholangitis. Yet, despite prior research efforts, the genetic loci, environmental elements and downstream interactions involved in the pathobiology of these diseases remain obscure. Thus, the development of novel and effective therapies to improve the quality of life and outcomes of these patients has been limited.
Over the past two decades, Dr. Lazaridis and his colleagues have created, and continued to maintain and expand, the largest research resource of people with primary biliary cholangitis and primary sclerosing cholangitis in the U.S. This resource is linked to curated clinical data and an expansive biorepository that includes samples derived from blood, urine, stool, saliva and liver tissue. This resource is critical for performing cutting-edge multi-omics studies aimed at better understanding underlying disease processes that may lead to the development of novel therapies.
The lab employs multi-omics-scale approaches to shed light on the underpinning mechanisms of these two enigmatic hepatic diseases. The foundation of the lab's experimental approach is the use of biological specimens collected from well-characterized patients with primary biliary cholangitis and primary sclerosing cholangitis, along with a pool of well-matched controls. These samples are used to generate large-scale multi-omics datasets to systematically investigate the genetic and environmental components that predispose people to primary biliary cholangitis and primary sclerosing cholangitis, as well as the downstream mechanisms that contribute to disease progression.
The Genomic and Exposomic Hepatobiology Laboratory is supported by National Institutes of Health grants, the Halloran Family Foundation and Mayo Clinic.
Affiliations