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 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. However, up to now these studies were limited using biopsy tissue homogenates, making it difficult to discern the specific pathways activated in cell types. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network will bring 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 set out to mine our existing compendium of thousands of gene expression profiles from renal biopsy tissues to extract single cell signatures using advanced data mining tools. In parallel we will develop technologies in our laboratories towards single cell analysis of renal tissues and scale them down so that they can work on single cells extracted from small renal biopsies. 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 three dimensional context of the kidney using specific RNA staining techniques in the first phase of the project. In the second phase, the analytical strategies will be scaled up so that single cell profiles from specific groups of patients can be obtained in a robust and reproducible manner. 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 first KPMP funding cycle novel, cell type specific treatment targets are identified fueling the therapeutic pipelines of the future.
PROJECT NARRARTIVE Understanding the roles of the individual renal cell types in renal health and disease is critical to develop novel targeted therapies. The PREcision Medicine through IntErrogation of Rna in the kidnEy (PREMIERE) Network will bring investigators from three leading biomedical research institution together to define the gene expression profiles of renal cell types in their tissue and disease context.