When cells in the oral cavity undergo unfavorable alterations due to pathogen encounters, human diseases can arise. Therefore, we need a better understanding of the underlying molecular mechanisms to develop therapeutic interventions. A knowledge gap in the field arises from a lack of tools, limited access to human primary oral cells, and the loss of original cellular properties and protein interactions from experimentation. To overcome these barriers, my project aim is to create Yeast Two-Hybrid (Y2H) libraries from primary oral cells. We utilize Y2H since it is a well-established method to study protein-protein interactions and to identify novel protein interactions of target proteins. We have established two of these libraries, one from uninfected cells and the other from oncogenic Human Herpesvirus-8 (HHV-8) infected primary human oral cells. I am currently testing the quality of the two newly created libraries to make sure they contain a variety of expressed human genes in the oral cells. In the future, I hope to demonstrate the functionality of the new Y2H libraries by performing a proof-of-principle Y2H screen. The ultimate goal is to identify interaction partners of key oral factors and find out how they work together during host-pathogen interaction of oral cells.