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Advancing NASH Research with Mice: Best Practices and Applications of Westernized Diets

 
Taconic Biosciences hosted a NASH symposium that brought together researchers across academia and industry to discuss translational NASH modeling, particularly as embodied in Westernized diet through enrichment with fat, cholesterol, and fructose. 
 
Nonalcoholic fatty liver disease (NAFLD) is a complex spectrum of disorders ranging from simple benign steatosis to steatohepatitis (NASH) with fibrosis. NAFLD is increasingly common around the world, especially in Western nations. 
 
There are still no FDA-approved therapeutics for these metabolic diseases due to extremely high attrition in late-phase clinical trials, making the selection of appropriate preclinical research models critical for drug approval.
 
This symposium examined the translational value of different approaches, immune involvement in NASH, and the application of preclinical models toward the discovery and development of targeted therapies.
 
There are five featured speakers, including a keynote address presented by Dr. Michele Vacca on behalf of the LITMUS Group.
 
Select a session from the list below to get access to the on-demand presentation.

Featured Sessions

Welcome and Introduction to NASH Preclinical Modeling

Presented by Dr. Fred Beasley, Field Applications Scientist, Taconic Biosciences

Watch for a brief overview of the current state of NAFLD/NASH research. NAFLD is the most common chronic liver condition in Western populations, sometimes called the ‘Silent Epidemic’.

Dr. Beasley reviews the individual stages of NAFLD disease progression and available dietary models to induce NASH in rodents.

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Dietary Considerations to Optimize NASH in Rodent Models

Presented by Dr. Sridhar Radhakrishnan, Senior Scientist, Research Diets, Inc

Discover different diets commonly used for NAFLD/NASH development, their utility, and translatability in this presentation. Purified diets formulated with specific nutritional components can drive the entire spectrum of NAFLD in rodent models.

Dr. Radhakrishnan outlines different dietary approaches for NAFLD development in rodent models and discusses the time frames required for disease development and whether human-like NAFLD metabolic disease comorbidities develop.

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Identification of Antigens in Diet Induced Nonalcoholic Steatohepatitis

Presented by Dr. Arion Kennedy, Assistant Professor, Department of Molecular and Structural Biochemistry, North Carolina State University

Hear about novel findings for identification of NASH-associated liver antigens which may lead to the development of antigen-specific therapies for the prevention of NASH and severe chronic hepatic pathologies such as hepatic cellular carcinoma.

Dr. Kennedy’s research group investigated the mechanisms which drive the activation of hepatic CD8+ T cells in NASH. Her lab explored whether NASH is regulated by an antigen-driven process and alters the immunopeptidome in Taconic’s diet induced NASH B6 model.

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Bioactive Lipids in NASH Pathogenesis

Presented by Dr. Harmeet Malhi, Professor of Medicine and Physiology, Mayo Clinic

In this presentation, you will get a better understanding on the various classes of lipids that may mediate toxicity and identify actionable signaling pathways that may be therapeutic targets in NASH.

Dr. Malhi presents on related extracellular vesicles (EVs), emerging mediators of intercellular communication in NASH.

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Is There a Murine Model That Fully Recapitulates Human NASH? An Unbiased Bioinformatics Approach Proposed by the EU IMI2 LITMUS Consortium to Rank Pre-clinical Models Based on Proximity to Human Disease

Presented by Dr. Michele Vacca, on behalf of the EU-IMI2 LITMUS consortium and the University of Cambridge, Assistant Professor at the University of Bari (IT) and Principal Investigator at the Roger Williams Institute of Hepatology (UK)

Walk through the LITMUS consortium’s evaluation process to identify and rank NAFLD-relevant murine models in a retrospective review with comparison to human NASH.

The majority of preclinical NASH research is performed in rodents; nevertheless, the appropriate model for recapitulating human disease is yet uncertain. To address this major unmet need, the LITMUS Pre-clinical Group performed a wide-ranging retrospective review of commonly used murine models, comparing them to human NASH by using a complex bioinformatics pipeline based on:
1) metabolic phenotype
2) centralized liver histology
3) liver transcriptome benchmarked against human NASH.

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Fred Beasley, PhD

Field Applications Scientist, Taconic Biosciences

Sridhar Radhakrishnan, PhD

Senior Scientist, Research Diets

Arion Kennedy, PhD

Assistant Professor, North Carolina State University

Harmeet Malhi, MBBS

Professor of Medicine and Physiology, Mayo Clinic

Michele Vacca, MD, PhD

Assistant Professor at the University of Bari (IT) and Principal Investigator at the Roger Williams Institute of Hepatology (UK), and member of the LITMUS European consortium

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