Precision medicine approaches have aimed to tailor medical decisions and interventions to fit the unique biochemical state of each individual, recognizing patient-to-patient variance influences disease penetrance, patient prognosis, and therapeutic outcomes. Despite early successes, a major challenge in advancing precision medicine is in the limitations of bulk measurement in accessible biofluids (plasma) which cannot accurately resolve the tissue origins of circulating molecules, critical for tracking organ-specific disease processes. The development of tissue-specific markers that reflect disease-relevant pathophysiology, capable of being sampled over time and condition and therapeutic intervention would be highly significant and impactful. Such approaches would revolutionize human precision medicine by enabling clinical detection/monitoring of tissue health and stress across organs in systemic chronic diseases.
In this talk we will discuss the strategy, pipeline and discovery of tissue-specific EVs, focusing on adipose and cardiomyocyte-derived EVs, profiling tissue-specific EV transcriptomics in cardiometabolic diseases, and using functional genomics methods to define clinical relevance. The integration of human multi-omics, imaging, human model systems, and discovery science to identify, characterize, and translate circulating markers of cellular states offers a path to improve understanding, detection, and treatment of human disease.
Apart from their potential as tools for liquid biopsy, EV-RNAs are increasingly recognized as novel mediators of interorgan communication. In the final section of the talk, we will explore the role of EV-RNAs in mediating cardiometabolic phenotypes by distal signaling between adipose tissue and other organs.