Project 2
Project 2 will investigate the role of a new genetic driver of focal segmental glomerulosclerosis (FSGS). Here single cell datasets, as in Project 1, will be generated at time points approximating the human postnatal development in control mice (for cross-species comparisons) and mouse model of FSGS (to find similarities in gene regulatory circuits with human FSGS).
Aim 1: Define cellular diversity, gene expression and the epigenetic landscape across the mouse kidney pediatric lifespan at timepoints relevant to kidney function and disease.
Aim 2: Determine cell states, expression signatures, pathways and gene regulatory mechanisms in a model of FSGS.
Principal Investigator
Michael I. Rauchman, MDCM
Chromalloy Professor of Medicine, Nephrology
Washington University in St. Louis School of Medicine
Michael Rauchman is a Professor of Medicine, Pediatrics and Developmental Biology at Washington University School of Medicine. He also serves as Section Chief of Nephrology at the St. Louis VA and directs a pediatric-to-adult transition clinic for kidney disease at Washington University. The main goal of his research is to investigate gene regulation during kidney development and disease. His lab applies this knowledge to understand birth defects of the kidney and to develop treatment strategies to promote repair and regeneration of the kidney in disease states. Ongoing studies are focusing on understanding how transcription factors and their associated chromatin remodeling complexes regulate cell fate of nephron progenitor cells during formation of the kidney. To identify novel genetic causes of congenital anomalies of the kidney and urinary tract (CAKUT), his research group and their collaborators are performing whole exome sequencing of parent-offspring trios comprising a child (fetus or newborn) with severe kidney defects identified on antenatal ultrasound. A second area of emphasis is to investigate epigenetic regulatory mechanisms of the kidney in response to acute and chronic disease. These studies are performed in mouse models and human tissues in collaboration with KPMP.
Co-Investigator
Michael Eadon, MD, PhD
Associate Professor of Medicine
Indiana University School of Medicine, Indianapolis, Indiana
Michael Eadon, MD, PhD is a translational physician scientist with accomplishments in the realms of pharmacogenomic discovery, construction of a molecular atlas of the kidney in health and disease, and implementation of pharmacogenomics and genomics of chronic kidney disease. He received his MD from Rush University (2006), completed internal medicine residency at Baylor College of Medicine (2009), and completed a combined research fellowship in nephrology, glomerulonephritis and clinical pharmacology at University of Chicago (2013). He joined Indiana University in 2013 and has appointments in nephrology, clinical pharmacology and medical & molecular genetics.
Eadon’s primary research efforts focus on the translation of pharmacogenomics into clinical practice as well as the identification of novel predictors of renal injury from large genomic and transcriptomic datasets. Major focus areas include the evaluation of renal disease expression patterns with spatial transcriptomics and understanding genetic variants that affect this expression (expression quantitative trait loci). He is an active member of NIDDK’s Kidney Precision Medicine Project and the Human BioMolecular Atlas Project, integrating diverse orthogonal datasets to characterize molecular patterns of kidney disease in subjects who have underwent a kidney biopsy.