Our lab uses quantitative approaches to understand how cells process stimuli to determine the appropriate functional response. Identifying the activating receptors, kinases and transcription factors that make up signaling pathways is necessary but not sufficient to predict how a cell will respond. It is important to understand how the level and activity of these pathway components are controlled in a context-dependent manner. For example, environmental and genetic factors can cause small variations in key signaling regulators. These quantitative changes may tune the sensitivity of cells to stimuli, setting the threshold for a functional response and influencing susceptibility to disease

A major focus of our lab is tuning of macrophage signaling and cytokine production. Many chronic inflammatory conditions have been linked to dysregulation of these responses. We study the signaling logic that helps macrophages discriminate low-level homeostatic stimuli from those of invasive infection. Our goal is to understand how this cellular decision-making and the resulting inflammatory thresholds are tuned in a context-specific manner. One such context is the tissue specific tuning of macrophage signaling at barrier sites including the lung and small intestine, where macrophages face ongoing exposure to the microbiota. Current projects are also interrogating the influence of aging on monocyte and macrophage signaling sensitivity and response dynamics. Our hope is that this work will yield insight into the cause of chronic inflammation in age-associated diseases, including cardiovascular disease and cancer.