Communication between different cell types is essential for the proper function of many human organs. What signals different cell types transfer between each other and how they respond to these signals is far from completely understood. This project studies the liver, which is one of the most important organs in the human body. Using a discovery-driven and inter-disciplinary approach, the goal of this project is to understand communications between the two main cell types in the liver, namely, hepatocytes and liver sinusoidal endothelial cells. The scientific objectives of the project are the following:
Objective I: Assemble three-dimensional liver mimics composed of hepatocytes and endothelial cells and collect temporal gene expression data using DNA microarrays.
Objective II: Compute molecular interaction networks that capture the response of hepatocytes and endothelial cells in liver mimics.
Intellectual Merit. The transformative nature of this project stems from the use of three-dimensional liver mimics to systematically probe and untangle the complex phenomena underlying cellular interactions in the liver. The integration of genome-wide transcriptional measurements in such liver mimics with molecular interaction networks will reveal the signals that mediate communications between hepatocytes and liver sinusoidal endothelial cells. Together, these studies will lead to deeper insights into the modes of interactions between cells types in the liver and their role in the maintenance of adult liver function.
Broader Impacts. A comprehensive understanding of biomimetic spatial organization and choreographed communication between different cell types has profound implications for tissue engineering. Information gleaned from this project will provide a sound theoretical basis for the design of the next generation of tissue-engineered livers.
Outreach to middle school students and to ethnically diverse female high school students through summer camps sponsored by Virginia Tech's Center for Enhancement in Engineering Diversity will introduce students to the notion of interdisciplinary research and demonstrate how collaborative advances in engineering and computer science can have a direct impact on human health.
The liver plays a critical role in maintaining health. This organ is responsible for the production of proteins, metabolism of glucose and cholesterol, detoxification or biotransformation of chemicals, and aids in digestion. In the liver, there are many different types of cells. Each of these cell types have specific roles, characteristics ad together, they coordinate liver functions. These cells are in constant communication with each other by receiving and sending signals. In this project we aimed to unearth some of the signaling pathways that result due to different cell types being in close proximity to each other. The liver model we assembled contained three of the four major liver cell types and therefore provided an ideal model to identify and analyze signaling mechanisms. This project contained both experimental and computational scientific aims. New computational approaches were designed to obtain information on cell signaling. We assembled liver-mimetic models, separated the cell types, extracted RNA, conducted microarray experiments, and analyzed the data using computational methods. The graduate students funded by this project were trained in the experimental and computational aspects and methods. We disseminated our results to the scientific community via peer-reviewed journal publications, presentations at national conferences, seminars at universities and in publicly available graduate theses.
