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Hyaluronan (HA) Synthesis Inhibition Normalizes Hepatic Fibrogenic Features by Reducing Hepatic Stellate Cell Activation in Alcohol-Associated Liver Disease Models

  • Published on September 22, 2020
  • Disease-Specific Resources
  • Test Systems & Methods
  • Webinars

Presenters: Michele Pritchard, Ph.D., Associate Professor, University of Kansas Medical Center and Maciej Czerwinski, Ph.D., Director of Consulting, SEKISUI XenoTech

In 2018, Dr. Pritchard published an abstract suggesting ethanol exposure sensitizes hepatic stellate cells (HSC) to activation stimuli resulting in enhanced pathogenic hyaluronan (HA) production. Targeting HSC hyaluronan production may therefore attenuate liver disease progression in alcohol-associated liver disease (ALD) patients.

Alcohol-associated liver disease (ALD) remains a pharmacologically incurable disease. Hyaluronan (HA), an extracellular matrix glycosaminoglycan, is increased in livers and blood of advanced liver disease patients who are actively drinking compared to those who do not drink. In the liver, hepatic stellate cells (HSCs) are responsible for most HA production, and HA synthesis is a prerequisite for fibroblast to myofibroblast transition. Further, increased HA content and fragmentation drive inflammation and fibrosis in many tissues. In this keynote, Dr. Pritchard will discuss how she and her colleagues tested the hypothesis that ethanol facilitates HSC activation through hyaluronan production in early ALD.

As a complementary presentation to Dr. Pritchard’s keynote, our in-house Director of Scientific Consulting, Dr. Maciej Czerwinski, will provide insight into pertinent test systems. SEKISUI XenoTech’s Research Biobank provides researchers with access to tissue microarrays (TMA) and liver tissue samples in various formats suitable for liver disease research. As a contributing author to Dr. Pritchard’s published abstract, and upcoming peer-reviewed publication, and resident expert for disease-state test systems, Dr. Czerwinski will provide details of the materials used and present an overview to the offerings and applications of Research Biobank tissue.

Key concepts discussed in the webinar:

  • Hyaluronan (HA) role in alcohol-associated liver disease (ALD)
  • Ethanol facilitation of hepatic stellate cell (HSC) activation through HA production early in ALD
  • Inhibiting HA synthesis in ALD mouse models
  • Tissue microarrays (TMAs) to evaluate HA and collagen content in steatotic livers
  • Research Biobank tissue applicability

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About the Presenters:

Dr. Michele Pritchard is an Associate Professor with tenure at the University of Kansas Medical Center in the Department of Pharmacology, Toxicology, and Therapeutics, and is also Associate Director of the Interdisciplinary Graduate Program in Biomedical Sciences. She received her Ph.D. in Immunology from the University at Buffalo in 2003 and conducted her postdoctoral research at Case Western Reserve University and the Cleveland Clinic. She has authored or co-authored more than 40 peer-reviewed publications in scientific journals including International Journal of Toxicology, Journal of Histochemistry & Cytochemistry, American Journal of Physiology. Gastrointestinal and Liver Physiology, and Hepatology. Her current research involves exploring hyaluronan biology in regenerative wound repair and fibrosis after tissue injury and during physiologic aging. The aim of Dr. Pritchard’s research is to identify ways to prevent organ fibrosis and to improve wound repair by targeting hyaluronan.

Dr. Maciej Czerwinski currently serves as a Director in the Scientific Consulting department at SEKISUI XenoTech. He received his Ph.D. from the University of Maryland at Baltimore Medical School in the Department of Pathology. Dr. Czerwinksi conducted his doctoral thesis research in the Laboratory of Dr. Frank Gonzalez at the National Cancer Institute in Bethesda, followed by a post-doc at the Department of Pharmaceutics, the University of Washington in Seattle. He has been with SEKISUI XenoTech since 1999 and guides the development of products and services for the in vitro analysis of drug safety. Dr. Czerwinski designed a patented method to analyze the in vitro cytokine-mediated drug-drug interactions between biologics and small molecule drugs, and he is also the inventor of SEKISUI XenoTech’s CryostaX single-freeze pooled hepatocytes.

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