Decoding Functional Cell-Cell Communication to Uncover Cellular State Modulation, Tissue Homeostasis, and Disease Genetics

About This Grant

7. PROJECT SUMMARY/ABSTRACT Although recent advancements in single cell and spatial transcriptomics have provided unprecedented resolution to study intercellular communication, there are currently still no comprehensive methods to fully decipher the complexity of truly functional cell-cell communication and to investigate its implications for human health and disease. The long-term goal is to reveal the complex networks of cell-cell communication to better understand their roles in maintaining tissue homeostasis, contributing to disease mechanisms, and ultimately guiding the development of novel therapeutic strategies. The overall objectives in this application are to 1) develop computational methods to systematically decipher functional cell-cell communication, and 2) investigate the regulatory roles of cell-cell communication in cellular states, tissue organization, and disease genetics. The rationale for this project is that while cell-cell communication is recognized as a fundamental aspect of tissue biology, its full complexity, especially in the context of disease, remains incompletely understood. By advancing computational methodologies and integrating multi-dimensional data, we can provide deeper insights into the mechanisms governing intercellular communication, which are crucial for both normal tissue function and disease progression. The central challenges will be addressed by pursuing three specific aims: 1) Develop innovative computational approaches to accurately define and categorize active cell- cell communication networks within tissues; 2) Systematically explore the impact of these communication networks on cellular states and tissue organization; and 3) Elucidate the functional contributions of cell-cell communication in the context of disease genetics. The research proposed in this application is innovative, in the applicant’s opinion, because it leverages cutting-edge computational and experimental techniques to integrate spatial and single-cell data, providing a multi-layered understanding of cell-cell communication. This approach allows for the creation of detailed communication maps and the identification of key regulators that could serve as targets for novel therapeutic interventions. This research is significant because it addresses a critical gap in our understanding of how cell-cell communication influences tissue function and disease systematically. By providing a comprehensive framework to study these communications, this project has the potential to transform our approach to understanding complex genetic diseases and to identify new therapeutic targets. Ultimately, such knowledge has the potential to offer new opportunities for the development of innovative therapies to treat genetic diseases, contributing to the broader field of precision medicine.