Jing Yu, PhD
Research in the Yu laboratory focuses on intercellular and intracellular mechanisms governing organ formation and regeneration, using the mammalian kidney as the model system.
The mammalian kidney is composed of the nephron and collecting duct epithelia, the vasculature and the interstitium. The coordination and interdependence of these structures are vital for both renal physiology and the formation of a functional kidney during development. Congenital anomalies and chronic renal and extrarenal diseases arise when the interplay and formation of these structures go away.
Three major research interests in the laboratory are renal medulla formation and repair, the regulation of collecting duct morphogenesis and differentiation by miRNAs, and the regulation of nephrogenesis by miRNAs.
The renal medulla plays a vital role in regulation of body water and salt homeostasis and in long-term regulation of systemic blood pressure. It is composed of medullary collecting ducts, the loops of Henle, vasa recta, a straight network of capillaries, and the medullary interstitium. It is often damaged in hydronephrosis that affects 1 in 100 in humans. We have recently identified a critical role of Wnt7b signaling in renal medulla formation. Our goal is to define the role of Wnt7b in the formation of each of the medullary components, to dissect the molecular and cellular machineries mediating Wnt7b signaling in the regulation of the formation of these components, and to determine the role of Wnt7b in the repair and regeneration of the damaged/disease renal medulla.
miRNAs are a family of small, non-coding RNAs that function mainly by inhibiting their target genes. We revealed critical roles of miRNAs in the formation of the renal collecting ducts and the nephron epithelia. We showed that miRNAs regulate ureteric bud branching morphogenesis, renal cyst formation, and collecting duct differentiation. Ureteric bud branching morphogenesis establishes the renal collecting duct system. Defective ureteric bud branching morphogenesis leads to renal agenesis/hypoplasia, and low nephron endowment, the latter being a predisposing factor for hypertension and chronic renal disease/renal failure. The cystic kidney disease (polycystic kidney disease) is the leading renal disease that affects 1 in 500 people in the United States. Our current research aims towards identification of the specific miRNAs and their target genes that are responsible for these defects, the mechanisms whereby the target genes regulate the developmental processes, and the developmental regulations of these miRNAs.
The epithelial components of hundreds of thousands of nephrons are formed during embryonic/fetal life from nephron progenitors through mesenchyma-to-epithelial transition. Nephon progenitor cells are stem cells that are multipotent and capable of self-renewal. We reported recently that miRNAs are vital for nephron progenitor self-renewal. Our future direction is to understand how miRNAs and their targets regulate nephron progenitor self-renewal.