Nolan Lab

Synopsis

We analyze cell signaling directly by next-generation mass cytometry and traditional flow cytometry, focusing on following multiple phosphoproteins in complex populations of primary cells such as mouse cells and human clinical samples. Using mass cytometry, up to 34 simultaneous protein parameters can be measured in single cells including multiple kinases, phosphoproteins, cell cycle proteins, and other parameters, enabling resolution of cellular activation states.

We are using these techniques to study healthy biochemical signaling in the immune system and dysfunctional signaling in hematological malignancies including AML, ALL, JMML, MDS, and follicular lymphoma. We have used this approach to distinguish predictive patterns of intracellular signaling to classify patient responses to chemotherapies and to determine how their signaling systems are altered in disease states. We are also using the technique for drug screening in primary cells to truly select for drugs with efficacies in certain cell subsets but not others.

Autoimmune diseases in which we have particular interest include rheumatoid arthritis and systemic lupus erythematosus. In these diseases, we focus on understanding how the immune system becomes dysregulated as as disease comes and goes. We can measure and determine the cellular network states in multiple cell subsets. In cancer, we are working in follicular lymphoma as well as acute myelogenous leukemia where we can look at disease progression as a measure of changes in disease states correlated to particular genetic changes in the genome of human cancer cells. Also we have made determined efforts in understanding how the cancerous microenvironment modulates immune signaling.

Published Experiments