Our lab investigates
molecular mechanisms of tissue injury, repair and fibrosis in the kidney
AND their Deleterious consequences for other organs
*interorgan-communication / Interorgan crosstalk*
Our Lab is interested in understanding cellular and molecular mechanisms that orchestrate tissue injury, repair and fibrosis in the kidney as well as deleterious effects of kidney disease in other organs (interorgan crosstalk).
Acute kidney injury (AKI) and fibrotic Chronic kidney disease (CKD) and their secondary complications, cardiovascular disease and lung injury, are highly prevalent world-wide and cause significant morbidity and mortality. Therapeutic strategies to prevent kidney injury or fibrosis and secondary organ damage are lacking.
Recently, we are particularly interested in kidney-released growth factors, cytokines and their receptors that control injury, repair and fibrosis in the kidney and that are involved in organ to organ crosstalk, such as the kidney-lung, kidney-heart or kidney-liver axis.
We are using mouse models of acute kidney injury and chronic kidney disease, combined with cardiac, lung or liver injury, as well as cell culture models. We are defining critical cell types and signaling mediators/pathways involved in tissue injury-repair, fibrosis and organ crosstalk using a combination of cell-based studies, genomic/bioinformatics analysis (shRNA, siRNA, CRISPR-Cas9, functional genomics, single cell RNAseq), novel genetically-engineered mouse models, clinical specimens, and targeted therapeutics.
In addition, we study the complex network of intracellular signaling pathways that regulate ectodomain cleavage by ADAM17, a transmembrane cell surface metalloprotease and key enzyme in the release of EGF ligands, of TNFalpha and of its receptors (among other substrates), all involved in tissue injury, repair and fibrosis in kidney, heart, lung, liver and other organs. Here, we are using computational analysis of a large shRNA dataset of cleavage regulators we generated, and validation of our findings in vitro and in vivo in kidney disease models.