Meetings

Cellular behaviors are governed by dynamic gene expression programs regulated at both the transcriptional and post-transcriptional level. However, our understanding of the gene regulatory mechanisms is far from complete. In this talk, I will discuss the role of RNA-dependent gene regulation in innate immunity and inflammation with a focus on the role of long noncoding RNAs in macrophage inflammatory response.

Innate immune signaling must be tightly regulated to support robust protective inflammatory responses to infection, while avoiding inflammation upon minor challenges. A fundamental challenge in inflammation research is to understand how signals are modulated to facilitate quantitative decision-making within cells.Quantitative trait loci for kinase and phosphatase genes have been linked with chronic inflammatory diseases of barrier sites, suggesting that modest expression changes in signaling components contribute to aberrant inflammation in humans. Changes in microbiota composition and other environmental factors are also associated with chronic inflammation in barrier tissues. A major focus of our lab is elucidating mechanisms supporting distinct regulation of macrophage signaling in the lung. Our current efforts include investigation of environmental factors that control lung-specific homeostatic cytokine expression, alveolar macrophage signaling proteins regulated by homeostatic cytokines, and mechanisms by which these proteins tune alveolar macrophage signaling and function. Understanding regulation and dysregulation of these processes will inform mechanistic links between disease-associated genetic factors, changes in the microbiota, and inflammatory disease development.

Chronic inflammatory liver disease is a major public health issue and is the 12th leading cause of death in the US. Despite major advances in the field, a clear understanding of which individuals are at risk to develop liver disease remains elusive and few effective therapies exist. Hepatic inflammation sets the stage of overt liver disease and the gut microbiota is a key player in liver pathologies. We are studying mechanisms how the gut microbiota impacts on the development of hepatic pathology by modulating hepatic immune responses.