Richard James's Biography

Richard James, Principal Investigator and Associate Professor, Seattle Children’s Research Institute and University of Washington

Cellular signaling is often thought of as a linear cascade of protein modifications in a single signaling pathway in response to environmental cues. My primary research interest is to understand how disease processes and pharmacological treatments alter cell signaling in immune diseases. To do so, we use a variety of approaches including quantitative proteomics and genome engineering to understand which signaling pathways are up-regulated during disease and in response to therapies. One focus of our lab is to understand how disease-associated exon-coding variants contribute to immune disease and cancer, by way of modeling variant effects in human immune cells. To that end, we have developed a novel approach that for the first time enables high-efficiency gene editing and gene delivery to in primary human B cells. More recently, my lab leveraged our genome engineering expertise and develop a cloning-free method for performing saturation genome editing in a diploid B cell line. This method enabled us to simultaneously query ~2500 variants in a region of CARD11, an adaptor gene associated with atopic immune dys-regulation. We used these data to re-classify several novel variants in this gene in patients from our clinic.