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 disease processes that contribute to the development and progression of the chronic cholestatic liver diseases primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).

PBC and PSC are rare chronic, progressive cholestatic liver diseases that contribute to hepatic failure and shorten patient life expectancy. PBC and PSC are likely caused by immune-mediated damage of cholangiocytes — the epithelial cells that line the bile ducts. Genetic and environmental factors are strongly suspected to significantly contribute to the etiologies of PBC and PSC. Yet, despite prior efforts, the genetic loci, environmental elements and downstream interactions involved in PBC and PSC pathobiology remain relatively obscure. Thus, the development of novel and effective therapies to improve patient quality of life and outcomes has been slow.

The lab employs omics-scale approaches to shed light on the underpinning mechanisms of these two enigmatic hepatic diseases. The foundation of our experimental approach is use of biological specimens collected from well-characterized patients with PBC and PSC along with a pool of well-matched, clinic-based controls. These samples are used to generate omics-scale data sets to systematically investigate the genetic and environmental components that predispose individuals to PBC and PSC, as well as the down-stream mechanisms that contribute to disease progression.

Over the past two decades, Dr. Lazaridis and his colleagues have created, and continue to maintain and expand the largest research resource of people with PBC and PSC in the U.S. This resource is linked to curated clinical data and an expansive biorepository, which includes samples derived from blood, urine, stool, saliva and liver tissue. This resource is critical for performing cutting-edge multiomic studies aimed to better understand underlying disease processes that may lead to the development of novel therapies.

The Genomic and Exposomic Hepatobiology Laboratory is supported by National Institutes of Health grants, the Halloran Family Foundation and Mayo Clinic.

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