Abstract SY19-03: Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics

Abstract

Abstract Intracellular assays of signaling systems has been limited by an inability to correlate functional subsets of cells in complex populations based on active kinase states or other nodal signaling junctions. Such correlations could be important to distinguish changes in signaling status that arise in rare cell subsets during functional activation or in disease manifestation. We have demonstrated the ability to simultaneously detect activated kinases and phosphoproteins in simultaneous pathways in subpopulations of complex cell populations by multi-parameter flow cytometric analysis, and now via high throughput mass spectrometry at the single cell level. The focus of the presentation will be our mechanistic studies of human Follicular Lymphoma, as well as signaling of “stem cell” like cell subsets in Acute Myelogenous Leukemia and other myeloid dysplasias. The detailed, correlated datasets generated via single cell phospho-flow allows for ready representation via automated signaling network determination using Bayesian analysis. Our pursuit of deep analysis of these datasets, and the limitations of cloud computing or standard multi-CPU systems, has stimulated our development of unique computational approach using field programmable gate arrays and GPU multiprocessor architectures in the development of a ‘bioinformatics supercomputer’ and associated algorithms. By analyzing the immune system, or cancer, as individual cells we now observe structured network interactions within these tissues at a new level of clarity. I will present our initial generations of comprehensive network topology maps of signaling within, and between, primary immune subsets in normal and pathologic disease tissues in cancer. My emphasis will be on the application of these approaches directly to human samples in near-patient settings for the development of point-of-care mechanistic referencing of disease and drug action. Citation Format: Garry P. Nolan. Single-cell signaling and pathology in primary cell cancers for mechanism and diagnostics [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY19-03