Rachel A. Gottschalk, PhD

Our lab uses quantitative approaches to understand how cells process stimuli to determine the appropriate functional response. Identifying the receptors, kinases, and transcription factors that make up signaling pathways is necessary but not sufficient to predict how a cell will respond. Context-dependent factors, such as tissue-specific stimuli, age, or genetic traits, can cause small variations in signaling components. These changes may tune the sensitivity of cells to stimuli, setting the threshold for a functional response and influencing susceptibility to disease

The major focus of our lab is understanding context-specific macrophage signaling and function. One such context is the tissue-specific tuning of macrophage signaling at barrier sites, where macrophages face ongoing exposure to the microbiota. These efforts involve modeling how lung-specific homeostatic cytokines impact regulation of macrophage signaling and gene expression, and investigation of novel signaling regulators that are highly expressed in the lung, but not other tissues. Current projects also include interrogating the influence of aging on monocyte and macrophage signaling sensitivity and response dynamics. Specifically, we are investigating whether monocytes from young and old humans or mice have distinct potential for functional polarization, in vitro and in mouse models of inflammation and resolution. We hope our efforts will bring us closer to predicting inflammatory response regulation based on context-specific gene expression, informing tissue-specific and age-specific therapeutic strategies.