Dynamic metabolic reprogramming in macrophages and neutrophils during functional transitions

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Talk abstract:

Innate immune cells like macrophages and neutrophils can sense a variety of molecular signals associated with infection or tissue damage, and undergo a series of functional changes in response. Emerging evidence suggests this process is associated with specific, substantial rewiring of cellular metabolism, which can both support and orchestrate changes in immune functions. Using a combination of multi-omics analysis, isotopic tracing-based flux analysis and genetic approaches, my laboratory works on quantitively characterizing the metabolic rewiring in macrophages and neutrophils and understanding its regulatory mechanism and functional significance. Specifically, here I will present two projects. The first project focuses on the multi-stage remodeling of mitochondrial metabolism in macrophages over a course of response to classical stimulation. This tightly regulated sequence of metabolic remodeling causes waves of rise-and-fall in immunoregulatory metabolites and their downstream signaling effectors, highlighting the highly dynamic nature of metabolic reprogramming during immune response. The second project focuses on the rapid shift towards pentose cycle with reversed upper glycolysis in activated neutrophils. This drastic metabolic shift is quantitively coupled to the oxidative burst and it demonstrates the impressive metabolic flexibility in neutrophils that is critical for their functions.