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We study innate immune signaling, immunometabolism and immune-nonimmune cell interactions in the context of tissues

nflammation, while essential to preserve life, introduces difficult challenges to cellular communities 
 within tissues. Activation of inflammatory processes is associated with recruitment of potent immune cells and dramatic tissue remodeling that may regulate fundamental cellular functions across lineages and time scales. Successful resolution of inflammation requires that tissues regain the optimal homeostatic framework coordinating normal tissue function. However, inflammatory changes that cause prolonged dysregulation of the tissue molecular and cellular configuration may ultimately lead to organ dysfunction. Our lab strives to better understand the impact of inflammation on cellular responses within tissues, particularly those involving macrophages and fibroblasts, with the goal of developing new therapeutic approaches for inflammatory bowel disease, sepsis and fibrosis.

Mapping tissue remodeling in colitis

Elucidating the tissue context of cellular responses during inflammation may help design better therapies for chronic inflammatory diseases. We recently used spatial transcriptomics and lineage tracing to map cellular distribution in the healthy and inflamed colon. Our study highlighted a surprising diversity of inflammation-associated fibroblasts, and suggested a staged progression of inflammatory tissue remodeling towards ulceration.

Programming intestinal tolerance

Within the intestinal tissue, diverse immune and non-immune cells coordinate protective responses against pathogens and pathological inflammation. By studying immunometabolism, innate immune circuits and functional crosstalk, we strive to identify the multicellular regulatory pathways controlling immune tolerance in the gut and their breakdown during chronic inflammation.

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Targeting systemic infection

If not contained by the immune system, bacterial or viral infection may cascade to devastating outcomes. The liver is a key integrator of antimicrobial responses and tolerance to circulating pathogens. By virtue of its metabolic and immunoregulatory functions, the liver plays a central role in protecting the host against detrimental immune responses that lead to sepsis and organ failure. Our lab aims to elucidate the cellular crosstalk in the liver that governs protective and pathological immune responses to systemic infection.

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