Education:

Ph.D., Biochemistry & Molecular Genetics, University of Louisville (2018)

 Research Areas and Projects:

The Hardesty laboratory is focused on identifying mechanisms of compromised liver regeneration and treatment options that restore liver regeneration and liver function in alcohol-associated liver disease (ALD) and steatotic liver disease (SLD). Liver diseases are thought to persist due to chronic inflammation that goes unresolved preventing liver regeneration. This is a common feature in multiple end-stage liver diseases for which there are no adequate treatments or therapies. Below are some ongoing projects in the Hardesty Lab.

Project 1: Restoring hepatic cardiolipin levels to promote liver regeneration in models of ALD and SLD. Our lab utilizes a hepatocyte cardiolipin deficient mouse model to establish the role of mitochondria dysfunction in compromised liver regeneration in ALD and SLD models. We also evaluate treatment molecules that 1) restore hepatic cardiolipin or 2) prevent hepatic cardiolipin oxidation as treatment strategies that promote liver regeneration in ALD and SLD.

Project 2: Improving liver function in end-stage liver diseases to reduce hypoalbuminemia. Hypoalbuminemia is a hallmark of end-stage liver diseases for which there is no effective treatment option. This project aims to determine if phosphoregulation of albumin is required for its secretion and if certain treatments can stimulate albumin phosphorylation and secretion.

Project 3: Identify markers and mechanisms of corticosteroid non-responsiveness in alcohol-associated hepatitis (AH). The current treatment strategy for AH is corticosteroids but unfortunately, not all patients respond to treatment (~40%). This project aims to identify mechanisms of steroid non-responsiveness in an animal model of AH. This will lead to the development of treatment options that will improve corticosteroid efficacy for AH patients.

Project 4: Determine cellular markers of compromised liver regeneration in end-stage liver disease using Visium Spatial Transcriptomic & Protein Analysis. Spatial transcriptomic analysis will be used to identify gene/protein signatures of hepatocyte proliferation in normal and diseased liver tissue. Findings from this study will help determine why liver regeneration is compromised or insufficient in many end-stage liver diseases.

Full List of Publications: https://www.ncbi.nlm.nih.gov/myncbi/josiah.hardesty.1/bibliography/public/