High throughput signaling pathway analysis during cellular organization into structures

Type of Award: Catalyst
Date Awarded: February 2010
Award End Date: January 2012
Amount Awarded: $ 200,000.00
PI(s): Lonnie Shea, PhD, Northwestern University; Debra Tonetti, PhD, University of Illinois at Chicago;

Abstract: Cells sense cues from the local environment and respond by initiating signals leading to a variety of cellular decisions such as cell growth, cell death, cell division or maturation. In cancer, an altered microenvironment may induce erroneous cellular responses, or the cell may erroneously respond to a normal environment. Quantifying the activity of the signaling pathways within normal and cancer cells as a function of the environmental cues may identify critical pathways leading to the formation of normal or abnormal tissue structures, which provides fundamental insight into the cell-environment interaction and could ultimately be used as a diagnostic in patient specific therapies. The proposed research to develop and apply a system to measure the signaling activity represents a collaboration between Prof. Shea, a bioengineer at Northwestern University and Prof. Tonetti at UIC, a breast cancer researcher. Prof Shea has developed a screening system that allows the defined modification of the extracellular environment and at the same time can detect and quantify multiple signaling pathways within cells, which will be expanded with the proposed research. Prof Tonetti has an extensive history of research involving signaling pathways in cancer cells, and has begun investigating the dependence upon the environmental context. This collaboration will apply defined microenvironments and the system for signaling pathway quantification to models of breast cancer to identify the pathways responsible for formation of normal and abnormal tissue structures, which have been observed in patients. Successful completion of these studies will lay the foundation to connect the microenvironment, cell signaling, and cellular responses to the organization of cells into functional tissues, which has numerous implications such as regenerative medicine, cancer, and stem cells. Additionally, this system has the potential to identify targets for therapeutic intervention and to understand the mechanistic basis of multiple diseases.