Managing calcineurin inhibitor-induced nephrotoxicity for renoprotection (C04)

钙调磷酸酶抑制剂如环孢菌素A和他克莫司是广泛用于预防移植器官排斥反应的一线免疫抑制药物。尽管取得了成功，但肾毒性副作用（例如肾小球、血管和肾小管间质损伤）很常见。在这里，药物可能通过引起细胞应激和蛋白质质量控制途径的适应不良来影响蛋白质稳态。可能导致细胞保护和促凋亡反应之间的不平衡。该项目旨在了解钙调磷酸酶抑制下细胞蛋白质稳态的功能，并发现肾脏保护策略，例如小分子伴侣的应用。

Calcineurin inhibitors such as cyclosporin A and tacrolimus are first-line immunosuppressive drugs widely used to prevent rejection of transplanted organs. Despite their success, nephrotoxic side effects such as damage of the glomeruli, vasculature, and tubulointerstitium are common. Here, drugs may affect proteostasis by causing cell stress and maladaption of the pathways of protein quality control. A disequilibrium between cytoprotective and proapoptotic responses may result. This project aims at understanding the functions of cellular proteostasis under calcineurin inhibition, and at discovering renoprotective strategies such as the application of small molecular chaperones.