NowarskiLAB
We study what makes or breaks tissue inflammation with a focus on cytokine signaling, immunometabolism, and innate immune memory
nflammation, while essential to preserve life, introduces difficult challenges to cellular communities
within tissues. Activation of inflammatory processes in tissue macrophages, epithelial cells and fibroblasts can impact their connectivity and function at different time scales. Therefore, better understanding of the tissue immunological circuitry, and its rewiring during tissue perturbation, holds the key to unlock the principles underlying tissue inflammation, its prevention, and its pathological persistence. We strive to leverage these insights towards developing new therapeutic approaches for immune-mediated diseases.
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. Our recent study identified a metabolic switch that programs durable immune tolerance through macrophage-epithelial feedback.
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.
