BLR&D Research Career Scientist Award Application

BLR

• 批准号: 10451503
• 负责人: Zheng Dong
• 金额: --
• 依托单位: CHARLIE NORWOOD VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2027-03-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10451503
• 关键词: Acute Renal Failure with Renal Papillary Necrosis; Aging; Alternative Splicing; Apoptosis; Area; Autophagocytosis; Award; CHEK1 gene; Cancer Patient; Cardiovascular Diseases; Cell Cycle; Cell Death; Chronic Kidney Failure; Cilia; Cisplatin; Collaborations; Communication; DNA Damage; DNA Methylation; Development; Diabetes Mellitus; Diagnosis; Disease; Epigenetic Process; Fibroblasts; Funding; Grant; Health; Hypoxia; Impairment; Injury; Injury to Kidney; International; Kidney; Kidney Diseases; Laboratories; Lead; Malignant - descriptor; Medical; Mentors; MicroRNAs; Mitochondria; Mus; Natural regeneration; Nature; Normal tissue morphology; Pathogenesis; Pathogenicity; Pathway interactions; Patients; Pharmaceutical Preparations; Principal Investigator; Profibrotic signal; Publishing; Regulation; Renal carcinoma; Renal tubule structure; Reperfusion Injury; Reperfusion Therapy; Reporting; Repression; Research; Research Personnel; Role; STAT1 gene; Science; Scientist; Seminal; Services; Signal Pathway; TP53 gene; Time; Training; Tubular formation; United States National Institutes of Health; Veterans; Work; aging population; cancer therapy; career; chemotherapy; diabetic; diabetic patient; epigenetic regulation; hypoxia inducible factor 1; indexing; injury and repair; insight; interstitial; kidney fibrosis; mitochondrial metabolism; mortality; nephrotoxicity; new therapeutic target; novel; novel therapeutic intervention; novel therapeutics; renal ischemia; response

Dr. Dong is a nationally and internationally recognized investigator in the research field of kidney injury and repair. His current work is focused on mitochondria, metabolism, autophagy, and epigenetic regulation in kidney injury and repair under the disease conditions of renal ischemia- reperfusion, diabetes, and cisplatin nephrotoxicity. As of July 1, 2019, Dr. Dong has published 256 research articles that have been cited for over 20,000 times with H-index of 66, attesting his scientific contributions. Dr. Dong is currently the principal investigator on a VA Merit review award and two NIH RO1 grants. In the project of the VA Merit review award, Dr. Dong and colleagues will elucidate the mechanism of renal fibrosis after ischemia-reperfusion injury. Specifically, they will determine the role of renal tubular autophagy in kidney fibrosis after ischemia-reperfusion injury, delineate the involvement of hypoxia-inducible factor 1 (HIF-1) in autophagy activation, and identify the key profibrotic factors that are produced in renal tubules in an autophagy-dependent manner for interstitial fibroblast activation. By elucidating tubular autophagy in renal fibrosis after ischemia- reperfusion injury, this project may lead to the discovery of new therapeutic strategies. In the project of NIH 5R01DK058831, Dr. Dong and colleagues propose to investigate the mechanism underlying the heightened kidney injury sensitivity in diabetes. They will specifically determine the role of p53 in miR-214 induction in diabetic kidneys, delineate microRNA-214 (miR- 214) repression of ULK1, and elucidate autophagy impairment as a key to injury sensitivity in diabetic kidneys. Completion of this project will delineate a novel pathway of p53/miR- 214/ULK1 that leads to autophagy impairment and kidney injury sensitivity in diabetes. As a result, it may identify miR-214 and autophagy as novel therapeutic targets for kidney injury in diabetic patients. In the project of NIH 5R01DK087843, Dr. Dong and colleagues will investigate nephrotoxicity induced by cisplatin, one of the most widely used cancer therapy drugs. Specifically, they will elucidate mitophagy as a protective mechanism of autophagy in cisplatin-induced nephrotoxicity, determine the autophagy-promoting role of p53, and analyze the effects of PKCδ inhibition in autophagy-suppressed and non-suppressed mice. The research will not only gain insights into autophagy protection and regulation in renal pathogenesis, but will also elucidate autophagy as a mechanism of the renoprotective effect of PKCδ inhibition, suggesting novel therapeutic strategies for kidney protection during chemotherapy in cancer patients. In conclusion, Dr. Dong is an outstanding investigator who has made seminal contributions to the research field of kidney injury and repair, which are highly relevant to veterans’ health. In the ongoing projects funded by VA Merit and two NIH R01 grants, Dr. Dong will continue to make important discoveries that may lead to novel therapies for kidney diseases for the improvement of veterans’ health.

董博士是国内和国际公认的肾脏研究领域的研究者 损伤和修复。他目前的工作主要集中在线粒体，代谢，自噬， 肾缺血疾病条件下肾损伤和修复的表观遗传调节- 再灌注、糖尿病和顺铂肾毒性。截至2019年7月1日，董博士已发表 256篇研究论文被引用超过20，000次，H指数为66，证明了他的 科学贡献。Dong博士目前是VA Merit评审奖的主要研究者 和两个NIH RO 1赠款。 在退伍军人管理局优秀评审奖的项目中，董博士和他的同事将阐明 缺血再灌注损伤后肾纤维化的机制具体来说，他们将确定 肾小管自噬在缺血-再灌注损伤后肾纤维化中的作用， 缺氧诱导因子1（HIF-1）参与自噬激活，并确定关键 在肾小管中以自噬依赖性方式产生的促纤维化因子， 间质成纤维细胞活化。通过阐明缺血后肾纤维化中的肾小管自噬- 再灌注损伤，该项目可能会导致新的治疗策略的发现。 在NIH 5 R 01 DK 058831项目中，Dong博士及其同事提议研究 糖尿病肾损伤敏感性增高的潜在机制。他们将专门 确定p53在糖尿病肾脏中miR-214诱导中的作用，描绘microRNA-214（miR-214）， 214)抑制ULK 1，并阐明自噬损伤作为损伤敏感性的关键， 糖尿病肾病该项目的完成将描绘p53/miR- 214/ULK 1的新途径 导致糖尿病患者的自噬损伤和肾损伤敏感性。因此，它可能 确定miR-214和自噬作为糖尿病患者肾损伤的新治疗靶点。 在NIH 5 R 01 DK 087843项目中，Dong博士及其同事将研究肾毒性 顺铂是最广泛使用的癌症治疗药物之一。具体来说，他们将 阐明线粒体自噬作为顺铂诱导肾毒性中自噬保护机制， 确定p53的自噬促进作用，并分析PKCδ抑制在 自噬抑制和非抑制小鼠。这项研究不仅可以深入了解 自噬保护和调节在肾脏发病机制，但也将阐明自噬， PKCδ抑制的肾保护作用的机制，提示新的治疗 癌症患者化疗期间的肾脏保护策略。 总而言之，董博士是一位杰出的研究者，他对以下方面做出了开创性的贡献： 与退伍军人健康密切相关的肾损伤与修复研究领域。在 由VA Merit和两个NIH R 01赠款资助的正在进行的项目，董博士将继续 重要发现，可能导致肾脏疾病的新疗法， 退伍军人的健康。