Resource Development Core

Mayo Clinic Rochester, Rochester MN

Investigators

Abstract

SUMMARY: MAYO RESOURCE DEVELOPMENT CORE (RDC) As described in the RFA of the Polycystic Kidney Disease Core Centers (U54), “the overall goal of the RDC is to establish and nurture a dynamic ‘incubator space’ that promotes innovation and ensures robust validation of new resources” and “a RDC is expected to demonstrate innovative strategies and capabilities to develop novel tools, models, and technologies”. Therefore, the objectives of the Mayo RDC are to provide this incubator space for Mayo investigators to explore new approaches through the development of expertise from their laboratories and the institution. The development and application of new technologies and methods is central to groundbreaking discoveries that lead to a better understanding of disease pathogenesis and the development of new therapies for PKD. Despite substantial progress in the identification of new disease- causing genes, variants, and molecular etiologies, there are limited targeted therapeutics and a deficiency of molecular biomarkers for ADPKD that can predict disease severity and progression as well as response to therapy. In addition, there are limited human ADPKD model systems that are valuable for understanding pathogenesis and testing new therapies. The extensive expertise and capabilities of Mayo Clinic Polycystic Kidney Disease Research Core Center (MPRC) investigators in state-of-the-art technologies and methodologies, and experience, knowhow and equipment of Mayo Clinic institutional cores illustrate potential areas to explore in the Mayo Resource Development Core (RDC). Although we note that the specific areas to be explored will be determined by the PKD-RRC Steering Committee. Areas of focus where we have specific expertise and experience that could be developed in this Core are to: 1) Develop reagents to enable genome editing in ADPKD, to target a range of ADPKD point and truncated mutations to facilitate specific and precise therapeutic strategies based on each patient's unique genetic makeup; 2) Develop PKD models of human stem cell-derived kidney organoids, to better model and test gene based therapies for the human disease; 3) Develop advanced imaging acquisitions and artificial intelligence (AI)-based image analysis software to monitor the progression of PKD, to more precisely determine disease severity; and 4) Develop capabilities for biomarker detection with cell free (cf)DNA and metabolomics approaches, to identify novel biomarkers in ADPKD. These areas are highlighted not only because of Mayo expertise in these areas but also the high potential impact if significant developments are made in any of these areas. The generation and sharing of new cutting-edge reagents and techniques are central to the development of novel therapeutic strategies and accurate monitoring of disease progression and response to treatments in ADPKD.