Details of Research Project:

Title: Hippo pathway signaling in podocyte injury and glomerular disease

Our lab has identified Hippo pathway upstream regulator KIBRA (Kidney BRAin) protein as a novel mediator of podocyte injury via inhibition of downstream pro-survival transcriptional co-activator YAP. Our previous work has demonstrated that upregulated KIBRA podocyte expression increases susceptibility to a murine model of FSGS and also that (the gene encoding KIBRA) is a risk gene for glomerular disease progression in human podocytopathies. Preliminary data suggests that increased KIBRA/Hippo pathway activation enhances podocyte injury in a diabetic milieu. We aim to test this hypothesis and the potential therapeutic role of small molecule Hippo mediators using complementary models including immortalized podocytes, hIPSC-derived podocytes and kidney organoids, diabetic rodent models, and banked human kidney tissue/biosamples. Other aims ...