Overview
A broad goal of our laboratory is to begin to understand how regulation of intestinal gene expression influences the pathogenesis of enteric inflammation. We are interested in the molecular mechanisms of cross-talk between transcription factors that are typically associated with changes in gene expression in response to inflammation, and those that control genes that regulate development and regeneration of cells in the intestine. These efforts will provide insight into the coordinated responses of the intestine to the damaging effects of uncontrolled inflammation or infection as well as the subsequent manner in which tissue repair is initiated.
In order to address this, we have chosen two overlapping focus areas that involve clinically important signaling pathways and transcription factors:
- We are studying a transcription factor family called NF-κB and its role in controlling intestinal gene expression during inflammation and tissue repair. We have shown that NF-κB activity in intestinal epithelia is required for suppression of acute inflammation as well as for healing of the damaged epithelial cell layer. Current work is directed at identifying the set of NF-κB-regulated genes that provide this protective effect as well as determining the cellular signals that control this aspect of NF-κB function.
- We are investigating the role of a cellular signaling protein called GSK-3β in coordinating the interplay between NF-κB and the other transcription factors such as AP-1 and β-catenin. Our work has demonstrated that GSK-3 is able to control which sets of stress-induced genes are expressed, in part, by controlling how these transcription factors interact in the nucleus of intestinal epithelial cells. Collaborative studies designed to determine the consequences of loss of GSK-3β within the context of intestinal inflammation are currently being pursued.
The work in our laboratory utilizes both molecular approaches such as chromatin immunoprecipitation and microarray analysis, as well as unique intestine-specific knockout mice that lack either NF-κB or GSK-3β activity. By using this combined approach, we hope to gain insight into the way in which the cooperative activity of these proteins controls the course of acute intestinal inflammation and subsequent repair and healing.
Find Dr. Steinbrecher's publications as listed by PubMed
Eleana Marie Harmel-Laws is a Research Assistant III in Dr. Steinbrecher's laboratory. She received her Masters of Science degree from the University of Kentucky in 2004 for analysis of the effects of PCB exposure on liver function of freshwater fish. Her current work is directed toward understanding the protective role of epithelial NF-κB in intestinal inflammation.
eleana.laws@cchmc.orgg
Position Available
A postdoctoral position is currently open in Dr. Steinbrecher's laboratory.
Contact Us
Kris A. Steinbrecher, PhD
Assistant Professor of Pediatrics
Division of Gastroenterology, Hepatology, and Nutrition
Cincinnati Children's Hospital Medical Center
MLC 2010
3333 Burnet Avenue Cincinnati, OH 45229-3039
Email kris.steinbrecher@cchmc.org
Phone 513-636-2416
Fax 513-636-5581
