Rawls Lab at Duke University
How do microbes impact the functions of host intestinal epithelial cells?
The microbiome is the diverse community of microscopic organisms that colonize different regions of our bodies. In the Rawls Lab, we are interested in how the intestinal microbiome impacts diverse aspects of host physiology, including intestinal function and what goes wrong during inflammation and disease.
My goal is to better understand the interactions between commensal intestinal microbes and the cells that line the intestinal epithelium. Specifically, I'd like to find out how bacteria or bacterial products regulate the activity of transcription factors which are central to functions of the intestinal epithelium such as nutrient absorption and defense.
My goal is to better understand the interactions between commensal intestinal microbes and the cells that line the intestinal epithelium. Specifically, I'd like to find out how bacteria or bacterial products regulate the activity of transcription factors which are central to functions of the intestinal epithelium such as nutrient absorption and defense.
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To address these questions I am using the zebrafish model system. The advantages of using zebrafish for these studies a multifold. We can raise large numbers of animals at once, make them germfree on-demand, and have precise control of their microbial communities.
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Zebrafish larva with a transgene labeling the anterior intestine (blue).
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My work focused on the HNF4 family of nuclear receptor transcription factors. Our lab previously found the HNF4 family member activity responds to the intestinal microbial community. Some of the questions I am endeavoring to address are: What are the microbial and host signaling pathways that induce changes in HNF4 activity? What are the roles of the different HNF4 family members in microbial response? and What are the consequences of loss of these factors for the host?
Publications
Heppert JK, Lickwar CR, Tillman MC, Davis BR, Davison JM, Lu HY, Chen W, Busch-Nentwich EM, Corcoran DL, Rawls JF. Conserved roles for Hnf4 family transcription factors in zebrafish development and intestinal function. Genetics. 2022 Oct 11:iyac133. doi: 10.1093/genetics/iyac133. Epub ahead of print. PMID: 36218393.
Heppert, J.K., and Davison, J.M., Kelly C., Rawls, J.F. Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium. (2020) Nature Reviews Gastroenterology and Hepatology. https://doi.org/10.1038/s41575-020-00357-6
Heppert, J.K., and Davison, J.M., Kelly C., Rawls, J.F. Transcriptional programmes underlying cellular identity and microbial responsiveness in the intestinal epithelium. (2020) Nature Reviews Gastroenterology and Hepatology. https://doi.org/10.1038/s41575-020-00357-6
