Inflammation is essential for host defense during infection,and may also be critical in the regulation of homeostatic functions in manytissues.  However, chronicinflammation is associated with a variety of diseased conditions such asobesity, diabetes, cancer and autoimmunity.  Macrophages constitute the most important cell type in the initiation and elaboration of inflammatory processes.  Consistent with the complexity of inflammation, these cells are capable of many different functional programs, including antimicrobial defense, tissue repair, phagocytosis, and regulation of metabolism.  We are interested in the transcriptional regulation of these functional programs, which will be key to understanding and manipulating inflammation and macrophage biology.  We believe that many of these functional programs are encoded by dedicated sets of genes, comprising distinct transcriptional modules that are each regulated by common transcriptional and epigenetic mechanisms.  Our goal is to characterize these modules; to identify the transcriptional masterregulators and epigenetic mechanisms that control their expression; and to understand how they are targeted by physiological regulators of macrophage biology and inflammation.

We are intrigued by the idea that inflammation is in many ways a fundamental mechanism of adaptive stress.  A related focus of the lab is on the reciprocal regulation of inflammation and the stress response, at the level of gene regulation.  We are interested in a group of transcription factors that are directly activated by different types of cellular stress and are therefore pivotally positioned to couple stress and inflammatory gene expression programs. We are also exploring the hypothesis that stress signaling may have a role in establishing inflammatory set points, such that prior exposure to cellular stress may alter subsequent inflammatory modalities.  At the molecular level, this is an epigenetic event that should be reflected in changes in the chromatin of inflammatory genes.