Proteotoxic Stress Responses and Inflammation a Vicious Interplay in Liver Disease




Pranoti Mandrekar, PhD


University of Massachusetts Medical School








The physiological function of the liver is elimination of pathogens and antigens from the blood for which mounting of an immune response is required. To avoid unnecessary activation of the immune system, the liver develops a local immune response followed by induction of peripheral tolerance towards the antigen. When stressful agents such as pathogens or environmental insults challenge the liver for extended periods of time and their elimination is not possible, inflammation and injury follows. The onset of inflammation in the liver is followed by fibrosis, cirrhosis and liver cancer. Thus, studying the mechanisms involved in liver inflammation will provide major insights into pathogenesis of liver disease and progression.

Using various in vivo and in vitro models, we are studying the role of innate immune signaling pathways, their crosstalk with oxidative stress mechanisms leading to pro-inflammatory cytokine production. My presentation will focus on novel mechanisms related to proteotoxic stress responses in the liver and their role in inflammation and fibrosis. Specifically, the role of stress proteins heat shock factor1 (HSF1) and target proteins HSP70 and HSP90 in fatty liver and inflammation, as well as repurposing of HSP90 inhibitors in alleviating liver inflammation will be discussed. 


Suggested Readings

Ambade et. al. J. Hepatol 2014.pdf Inhibition of heat shock protein 90 alleviates steatosis and macrophage activation in murine alcoholic liver injury
Muralidharan and Mandrekar-JLB 2013 Review.pdf Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation

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