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microRNAs: Novel Players in the Regulation of Endodontic Disease

Sheng Zhong: microRNAs: Novel Players in the Regulation of Endodontic Disease (Under the direction of Dr. Asma Khan) The purpose of this project was to examine the role of microRNA (miRNA) in endodontic disease. We tested the hypotheses that miRNAs are differentially expressed in infected pulps as compared to normal pulps and that exposure to lipopolysaccharide (LPS) induces changes in macrophage miRNA expression. miRNA expression in normal and infected human pulps (N=28) was profiled using microarray technology. Next CD14 positive monocytes isolated from fresh human buffy coats, and induced towards a macrophage phenotype were challenged with E. coli LPS for up to 8 hours and miRNAs expression was quantified using Nanostring technology. Of the 348 miRNAs expressed in the pulps, 36 were altered in infected pulps (p<0.003). The potential gene targets for these miRNAs included key mediators of the immune response. LPS challenge resulted in time-dependent changes in miRNA expression. Together our data provide support for the role of miRNAs in endodontic disease. iv Acknowledgements This thesis would not have been possible without the guidance and limitless help of my thesis committee. Special thanks to Dr. Asma Khan for leading the research project and her generous support throughout the study. A very special thank you goes to Dr. Salvador Nares for sharing his lab with us and guiding me through the study. I sincerely appreciate Dr. Eric Bair's statistical support and timely response to all of our questions. At the end, I would like to thank all the people involved in this study. It was you who made this journey such a wonderful experience.