Our lab investigates the regulation and roles of growth factors
in kidney function and IN the development of KIDNEY disease.
Growth factors and their receptors have been a focus of research for decades. We have learned much about the structure of receptors and ligands, the intracellular pathways they activate and the target genes they address. What is less well understood is the fine regulation in the organism that depends on synthesis, processing and release of growth factors (or receptors) by metalloprotease cleavage (Ectodomain shedding) or by other mechanisms in different cell types.
The kidney is a prime example for the participation of epithelial and endothelial cells, as well as fibroblasts and cells of the immune system in factor release. In the kidney, ADAM-mediated release of EGF Ligands induces EGFR activation which is important for tubular repair after injury. However, when EGFR activation is sustained by severe injury, or repeated chronic injury, it leads to fibrosis. The high prevalence and burden of fibrotic chronic kidney disease (CKD) is well established world-wide. However, therapeutic strategies to prevent fibrosis are lacking.
Our lab investigates regulation and release of growth factors in kidney disease using mouse models of acute kidney injury and chronic kidney disease as well as cell culture models. We study the complex network of intracellular signaling pathways that regulate ectodomain cleavage using biocomputational analysis of a large shRNA dataset of TGFalpha cleavage regulators we generated, and by validating our findings in vitro and in vivo in kidney disease as well as cancer models.