PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE)

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ABSTRACT The kidney has developed a complex, three-dimensional architecture to serve its key functions, including excretion of waste substances, maintenance of the internal balance for fluid and salt, blood pressure control, and hormonal function. Understanding the roles of the individual renal cell types and cell states in these processes in health and disease is critical to develop novel targeted therapies. Extensive studies lead by this investigative group and others have started to identify molecular disease mechanism in renal biopsy tissues and helped to develop novel disease markers and therapies. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network has brought investigators from three leading biomedical research institutions with diverse, complementary expertise together. Our team has an established track record in working jointly to develop state of the art approaches in molecular analysis of renal disease. We will continue to perform high-quality, high-throughput single cell RNA sequencing on research biopsies from the Kidney Precision Medicine Project and advance the technology for deeper sequence coverage, reduce cost, use smaller biopsy portions without data loss so that additional technologies can be employed across KPMP, in a robust and reproducible manner. These single cell profiles will be linked to the disease states of the patients. Key signatures associated with specific cells and diseases will be extracted and localized in the spatial context of the kidney using specific, highly multiplexed RNA staining techniques. Additionally, we will employ cutting edge spatial transcriptomic technology to map cell clusters to their local environment for an added dimension of disease understanding. To this end the PREMIERE investigators will work closely with the tissue procurement sites and the Central Hub of the KPMP, using their 20 years of experience in team science, so that at the end of the KPMP funding cycle, novel cell type specific treatment targets are identified fueling the therapeutic pipelines of the future.