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Engineering and Technology

BMCE Faculty Candidate: Targeting Macrophage Persistence to Prevent Progression of Chronic Kidney Disease

January 9, 2020 at 9:30am10:30am EST

Bowne Hall, 414

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Leyuan Xu, Ph.D., from Yale University, is a candidate for a faculty position in the Department of Biomedical and Chemical Engineering, part of the cluster hiring initiative in the BioInspired Institute.

Abstract: The global burden of chronic kidney disease (CKD) remains high with clear unmet medical needs. Acute kidney injury (AKI) significantly increases the risk of developing progressive fibrosis and CKD. Macrophages play complex roles in AKI, with classically activated proinflammatory macrophages initially serving for clearance of apoptotic cells and debris after injury, and alternatively activated reparative macrophages promoting tubule repair followed by either egress or apoptosis of the macrophages in the event of adaptive repair. However, failure to achieve tubular repair after AKI leads to abnormal intrarenal accumulation of profibrotic macrophages, which in turn promote kidney fibrosis and recruit dendritic cells and T cells into kidney interstitium. This exaggerated immune response results sustained kidney injury, reduced tubule regeneration, and kidney atrophy in the setting of maladaptive kidney repair. Targeting macrophage persistence may slow, or even prevent, CKD progression. However, prolonged systemic administration of drugs that block macrophage function may increase the risk of developing chronic infections. Nanomedicines have been the subject of great interest for the targeted treatment of organ or cell-type specific diseases. Among these, dendrimers are a unique class of macromolecules comprised of a highly branched three-dimensional architecture with low polydispersity and a high degree of functionality, and they play an important role in the emerging field of nanomedicine. Due to their unique physiochemical properties, dendrimers hold great potential for kidney-specific drug delivery in overcoming three glomerular barriers, i.e., endothelium, glomerular basement membrane (GBM) and foot processes of podocytes.

This event was first published on January 6, 2020 and last updated on January 10, 2020.

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