The Liver Disease Immunobiology Lab led by Petra Hirsova, Pharm.D., Ph.D., at Mayo Clinic is interested in several areas:
Immune mechanism and T cell pathogenicity in nonalcoholic steatohepatitis (NASH). Affecting an estimated 5% of the U.S. population, NASH has become a significant public health concern. Due to the current lack of effective pharmacotherapies for NASH, there is a great need to better understand the molecular and cellular mechanisms involved in the NASH pathogenesis, which, in turn, would guide designing novel therapeutic strategies.
Our studies to date have explored immune mechanisms driving the onset and progression of NASH, demonstrating that both innate and adaptive immune systems play critical roles in disease pathogenesis. In addition, inhibition of these immune mechanisms has beneficial effects in murine models of NASH, highlighting that these approaches have a great potential to be translated to patient care. Our current work investigates the roles of various T cell subsets and T cell-mediated responses in NASH development.
- Cell-to-cell communication. Cell-to-cell communication is a vital process for any multicellular organism. It is now well recognized that cells communicate not only by direct contact and soluble factors but also via nanometer-sized membrane-bound vesicles termed extracellular vesicles. Dr. Hirsova's lab investigates crosstalk between different cell types mediated by extracellular vesicles during liver pathologies. Insights into pathological intercellular communication can uncover specific targets for therapeutic strategies for liver pathologies.
- Stress-induced signaling and cell death. NASH is characterized by cellular stress induced by toxic lipid intermediates. Unmitigated cellular stress can eventually lead to cell death. Both cellular stress and excessive death of hepatic cells can trigger liver pathologies. Dr. Hirsova is particularly interested in molecular mechanisms and consequences of lipid-induced cellular stress and death of liver parenchymal cells during NASH pathogenesis.
- Link between intestinal and liver inflammation. The gut-liver axis refers to the bidirectional relationship between the gut and the liver, resulting from the integration of signals generated by dietary, genetic and environmental factors. The lab's collaborative work with Dr. Bamidele investigates how intestinal inflammation affects liver function and diseases.