Functional Genomics of Inflammation in Humans

Steve E. Calvano, Ph.D.,

University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, New Jersey

In analyses of microarray data, cluster and principal component approaches adequately describe overall changes in apparent gene expression, but they provide limited insights into the rich interactions that underlie cellular biological processes.  Using an in vivo human model of whole body inflammation induced by the intravenous administration of bacterial endotoxin, the transcriptional response of white blood cells was assessed over time by microarray technology.  Next, a structured network knowledge-base approach was developed and used to analyze this response in the context of known functional interrelationships among proteins, small molecules and phenotypes.  This new methodology revealed that the white blood cell response to an acute inflammation includes the transient dysregulation of leukocyte bioenergetics and modulation of its translational machinery.  The findings provide new insight into gene regulation in white blood cells and their subsets.