Immunology Faculty Member - Tiffany Horng, PhD
Tiffany Horng, PhD
Genetics & Complex Diseases
The lab is broadly interested in macrophage biology in multiple contexts including inflammatory bowel disease and metabolism. We are currently pursuing three lines of investigation relating to the functions of these cells.
One is centered on inflammasomes, cytosolic complexes that activate the proinflammatory caspase, Caspase-1, thus promoting maturation and release of IL-1b and IL-18. The inflammasome pathway has been linked to both adaptive and maladaptive inflammation in diverse settings, including host defense and metabolic diseases, yet there are major gaps in our understanding of inflammasome biology. We have recently described a role for calcium-mediated mitochondrial damage in activation of the NLRP3 inflammasome, and we continue to address mechanisms underlying inflammasome activation and regulation of their effector activities.
A second line of investigation is focused on macrophage polarization, and in particular M2/alternative polarization. We have recently described a role for a central metabolic pathway, the mTOR pathway, in control of macrophage polarization. We believe that the mTOR pathway can calibrate nutrient levels and metabolic input to macrophage polarization, and seek to elucidate the underlying basis. We are testing the relevance of this process for the function of adipose tissue macrophages, where M2 polarization has been shown to mediate adipocyte insulin sensitivity and metabolic homeostasis.
A final focus is on macrophages in the context of inflammatory bowel disease. IBD is characterized by chronic, remitting inflammation, and we are interested in the role of macrophages in sustaining chronic inflammation. Using the IL-10 knockout mouse model of colitis, we are testing the idea that macrophage-elaborated inflammatory responses can be reprogrammed during chronic inflammation, perhaps as a result of epigenetic changes. We also seek to characterize the mechanisms underlying sustained macrophage activation in this colitis model.
Last Update: 7/16/2014