Research interest

Analysis of transcriptional and post-transcriptional mechanisms regulating inflammatory gene expression.

Analysis of relationship between inflammation and cellular stress.

Current program

• Evaluation of mechanisms regulating mRNA half life during inflammatory response
• Role of upstream open reading frames in regulating cellular stress responses
• Signal transduction pathways coupling cell stress and inflammatory response in myeloid cells

Brief Description

The diversity of the inflammatory process stems from multiple sources, including the complexity of inflammatory stimuli and cell types, the transmembrane and intracellular signaling processes that occur following stimulation, and the large number of independently regulated genes whose expression is subject to modulation during the process.

The primary objective of our research program is to define the molecular events that control the expression of inducible genes during the initiation and resolution of inflammation. An emerging component of these studies includes consideration of the process of cellular stress, also known as the unfolded protein response or endoplasmic reticulum stress. Collectively our research efforts focus on alterations in transcription and mRNA metabolism that can produce significant changes in levels of inflammatory gene products such as chemoattractant cytokines (chemokines) and mediators of cellular stress. Although the mechanisms that increase inflammatory gene expression are important, it is equally necessary to understand negative regulation of these genes since the expression patterns are transient and inappropriate or prolonged expression often results in substantial tissue injury.

The goals of current projects include: (1) identification of mRNA sequence controlling instability and stimulus-induced stabilization, (2) definition of mechanisms through which mRNA decay is achieved, and (3) characterization of the signaling pathways through which inflammatory and cellular stress pathways communicate with one another.