Carsten Schultz and lab develop new imaging platform for profiling cell signaling networks

Dr. Carsten Schultz, chair of physiology and pharmacology, describes chemical tools he developed for manipulating and monitoring signaling that will advance OHSU's ability to study brain circuitry.

Cellular development, tissue repair, immunity, and normal homeostasis rely on cells perceiving and appropriately responding to their microenvironment. While significant knowledge exists on the individual aspects of these cell signaling pathways, the question persists on how cell signaling networks integrate and process information from multiple extracellular cues. Understanding these processes may help develop therapies to more effectively treat diseases such as cancer and diabetes that result from errors in processing information.

A study published December 8 by Carsten Schultz, Ph.D., chair of the OHSU School of Medicine’s Department of Physiology and Pharmacology, in Cell Chemical Biology reports development of a new imaging platform for monitoring cell signaling network activity that may, when combined with gene expression studies, answer long-standing questions about how this complex communication system works.

Dr. Schultz and his team developed a method that allows comprehensive system-level analysis of multiple signaling pathway dynamics under identical conditions. Such a method supports research into how cellular signaling networks integrate information from the extracellular environment, how they evoke specific cellular responses, and, most importantly, how normal signaling is rewired over the course of a disease.

The team combined cell microarray technology with Förster resonance energy transfer (FRET) biosensors and live-cell imaging. The study demonstrated that the platform enabled multi-dimensional data generation in a single experiment and successfully demonstrated the effect of perturbing the network by drugs. They also found that crosstalk of two growth factors produces distinct activity patterns.

The platform may in the future be applied to develop comprehensive models of signaling networks and help investigate the mechanisms of action, as well as side effects of therapeutic treatments. The findings may provide information relevant to disease progression and prognosis, design of therapeutic treatment, and drug discovery.

The research team included Dmitry Kuchenov, Vibor Laketa, and Frank Stein from the European Molecular Biology Laboratory (EMBL) Cell Biology and Biophysics Unit in Heidelberg, Germany, and Florian Salopiata and Ursula Klingmüller of the Translational Lung Research Center Heidelberg, a German Center for Lung Research site. Schultz joined OHSU in the fall of 2016 as chair of the Department of Physiology and Pharmacology.

The work was supported by the Schultz team at the European Molecular Biology Laboratory, the German Federal Ministry of Education and Research, the DFG (SFB 1129), and the Joachim Herz Foundation. The Klingmüller group was supported by the German Federal Ministry of Education and Research through the LungSysII consortium, and the German Center for Lung Research.