BLR&D Research Career Scientist Award Application

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.