Project Grant K08DK139369

TRANSCRIPTOMIC DIAGNOSIS AND STAGING OF SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY - ACUTE KIDNEY INJURY IS DIAGNOSED IN OVER 50% OF PATIENTS WITH SEPSIS. SEPSIS-ASSOCIATED AKI (SAKI) CONTRIBUTES TO HIGH MORTALITY, THE DEVELOPMENT OF CHRONIC KIDNEY DISEASE (CKD) AND END- STAGE RENAL DISEASE (ESRD). DESPITE DECADES OF INVESTIGATION INTO THE PATHOPHYSIOLOGY AND TREATMENT OF SEPSIS AND ASSOCIATED KIDNEY INJURY, WE REMAIN WITHOUT DIAGNOSTIC TOOLS TO STRATIFY HUMAN AKI ETIOLOGY AND STAGE, WHICH WE SEEK TO ADDRESS IN THIS PROPOSAL. THE OVERALL GOAL OF OUR PROJECT IS TO TEST THE HYPOTHESIS THAT MURINE BLOOD TRANSCRIPTOMICS CAN BE USED TO DIAGNOSE AND STAGE HUMAN SAKI. WE WILL FIRST IDENTIFY MURINE BLOOD-BASED BIOMARKERS(MIRNA AND MRNA) REFLECTIVE OF SAKI TISSUE INJURY. WE WILL THEN USE THE MURINE BIOMARKERS TO STRATIFY HUMAN AKI ACCORDING TO SAKI DIAGNOSIS AND MOLECULAR STAGE. THE IMMEDIATE OUTCOME OF THIS WORK WILL BE THE DEVELOPMENT OF A LIQUID BIOPSY TO DIAGNOSE AND STAGE HUMAN SAKI. INDIANA UNIVERSITY HOUSES THE BIOBANK COHORT OF INDIANA AND IS AN ESTABLISHED TISSUE INTERROGATION SITE FOR THE KIDNEY PRECISION MEDICINE PROJECT (KPMP), THUS, MY INTERDISCIPLINARY MENTORING TEAM AND I ARE WELL-POSITIONED TO UNDERTAKE THIS HIGHLY TRANSLATABLE WORK. THE CURRENT PROPOSAL WILL DEVELOP A NUMBER OF SKILLS REQUIRED TO BE A SUCCESSFUL, INDEPENDENT TRANSLATIONAL RESEARCHER. WHILE MY LONG-TERM GOAL IS TREATMENT OF SAKI, THE IMPLEMENTATION OF THIS NECESSITATES SOLID BASIC SCIENCE AND COMPUTATIONAL SKILL SETS. THIS WILL ALLOW FOR FUTURE WORK FOCUSED ON THE TREATMENT OF SAKI. IF THESE STUDIES SHOW EFFICACY IN THE DIAGNOSIS AND STAGING OF HUMAN AKI, THESE STRATEGIES MAY BE RAPIDLY TRANSLATED INTO THE CLINICAL SETTING.