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1. Delineate the mitochondrial pathway of apoptosis in hypoxic/ischemic kidney injury, discovered the role of Bak in the regulation of mitochondrial dynamics, and demonstrated the pathogenic role of mitochondrial dynamics disruption in kidney disease. Dr. Dong and his laboratory showed that the mitochondrial pathway is centered on the regulation of outer membrane permeabilization by Bcl-2 family proteins, resulting in the release of apoptogenic factors, such as cytochrome c. Their recent work further demonstrated a striking change of mitochondrial dynamics during cell injury and stress in diseases. They discovered a novel role of Bak in mitochondrial fragmentation and damage under cell stress and disease conditions. They further unveiled Bif-1 as a key regulator of mitochondrial inner membrane dynamics. These studies have been published in >50 research articles and have been cited for >6000 times. They have also contributed authoritative reviews in this field (eg. Zhan M. et. al. Kidney Int 2013; Linkermann et al. JASN 2014; Tang et al. Nature Rev Nephrol 2020). Representative original publications:

Representative Original Publications:

a. Brooks C, Wei Q, Feng L, Dong G, Tao Y, Mei L, Xie Z, Dong Z. Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with Mitofusins. Proceedings of National Academy of Sciences (USA) 104: 11649-11654, 2007. PMCID: PMC1913853 (Highlighted by Faculty 1000; with news report) 104: 11649-11654, 2007. PMCID: PMC1913853 (Highlighted by Faculty 1000; with news report).

b. Brooks C, Wei Q, Cho S, Dong Z. Regulation of mitochondrial dynamics in acute kidney injury in cell culture and rodent models. Journal of Clinical Investigation 119: 1275-85, 2009. PMCID: PMC2673870 (with news report).

c. Wei Q, Dong G, Chen J, Ramesh G, Dong Z. Role of Bax and Bak in ischemic acute kidney injury shown by global and proximal tubule-specific knockout mouse models. Kidney International 84:138-48, 2013. PMCID: PMC3686831.  

d. Cho S, Xiao X, Wang , Gao H, Rafikov R, Black S, Huang S, Ding HF, Yoon Y, Kirken RA, Yin XM, Wang H-G, Dong Z. Bif-1 interacts with prohibitin-2 to regulate mitochondrial inner membrane during cell stress and apoptosis. Journal of American Society of Nephrology 30:1174-1191, 2019. PMCID: PMC6622411 (Highlighted on Journal cover).

2. Unveil a rapid DNA damage response during cisplatin-induced nephrotoxicity and have further determined its pathogenic role. These findings have been verified by other investigators, leading to the recognition of the DNA damage response mediated by ATR/Chk2/p53 as an important pathogenic mechanism in cisplatin nephrotoxicity. The studies have been published in >40 research articles and have been cited for ~3000 times. We have also contributed authoritative reviews in this field (eg. Pabla N et al. Kidney Int 2008; Jiang M et al. JPET 2008; Yang Y et al. Arch Toxicol 2014; Zhu S et al. Arch Toxicol 2015; Tang C et al. Pharmacology & Therapeutics 2019; Tang et al. Nature Rev Nephrol 2023).

Representative Original Publications:

a. Pabla N, Ma Z, McIlhatton MA, Fishel R, Dong Z. hMSH2 recruits ATR to DNA damage sites for activation during DNA damage-induced apoptosis. Journal of Biological Chemistry 286:10411-8. 2011. (Highlighted by Faculty 1000)

b. Pabla N, Bhatt K, Dong Z. Chk1-S is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proceedings of National Academy of Sciences (USA) 109: 197-202, 2012. (news report) c. Zhang D, Liu Y, Wei Q, Huo Y, Liu K, Liu F, Dong Z. Tubular p53 regulates multiple genes to mediate acute kidney injury Journal of American Society of Nephrology 25 (10):2278-89, 2014 (Highlighted on journal cover)

d. Fu Y, Xiang Y, Han Y, Cai J, Duan S, Chen A, Dong Z. DUSP26 protects against acute kidney injury by dephosphorylating p53 at serine 312. Nature Communications 17, 3208, 2026.

3. Demonstrate the first evidence of autophagy in acute kidney injury and further establish its role in kidney injury and repair. This line of work has been verified and extended by other investigators to show the role and regulation of autophagy in other renal diseases, suggesting a therapeutic approach for kidney protection. The studies have been published in >40 research articles and have been cited for ~4000 times. Dr. Dong and his laboratory have also contributed authoritative reviews in this field (Periyasamy-Thandavan Set. al. AJP-Renal 2009; Huber et al. Autophagy 2012; Livingston et al. Seminar in Nephrol 2014; Tang et al. Nature Rev Nephrol. 2020).

Representative Original Publications:

a. Periyasamy-Thandavan S, Jiang M, Wei Q, Smith R, Yin X, Dong Z. Autophagy is cytoprotective during cisplatin injury of renal proximal tubular cells. Kidney International 74, 631–640, 2008. PMID: 18509315. (Highlighted by Editorial: Kidney Int 74, 555-7).

b. Jiang M, Wei Q, Dong G, Komatsu M, Su Y, Dong Z. Autophagy in proximal tubules protects against acute kidney injury. Kidney International 82: 1271-1283, 2012. (highlighted by Editorial: Kidney Int 82: 1250-3; also by Nature Rev Nephrol).

c. Livingston M, Ding H, Huang S, Hill J, Yin X, Dong Z. Persistent activation of autophagy in kidney tubular cells promotes renal interstitial fibrosis during unilateral ureteral obstruction. Autophagy 12:976-98, 2016.

d. Livingston Mang J, Ganley I, Yin X, Dong Z. Clearance of damaged mitochondria via mitophagy is important to the protective effect of ischemic preconditioning in kidneys. Autophagy 15(12):2142-2162, 2019

4. Report microRNA and DNA methylation as epigenetic mechanisms in ischemic and cisplatin nephrotoxic kidney injury. Dr. Dong and his laboratory have subsequently delineated the regulation of several specific microRNAs in kidney injury, protection, and repair. These studies, published in >30 research articles, have gained new insights into the pathogenesis of acute kidney injury and recovery, and have suggested novel therapeutic strategies by targeting epigenetics. They have also contributed several reviews (Bhatt et al. AJP-Renal 2011; Wei Q et al. IUBMB Life 2013; Kidney Int 2015; Guo C et al. Nature Rev Nephrol 2019).

Representative Original Publications:

a. Wei Q, Bhatt K, He H, Mi Q, Haase VH, Dong Z. Targeted deletion of Dicer from proximal tubules protects against ischemic acute kidney injury.  Journal of American Society of Nephrology 21: 756-761, 2010. PMCID: PMC2865746. (Highlighted on journal cover).

b. Guo C, Pei L, Xiao X, Wei Q, Chen JK, Ding HF, Huang S, Fan G, Shi H, Dong Z. DNA methylation protects against cisplatin-induced kidney injury by regulating specific genes, including interferon regulatory factor 8. Kidney International  92(5):1194-1205, 2017.

c. Wei Q, Sun H, Liu Y, Liu P, M.J. Livingston, Wang J, Liang M, Huo Y, Nahman S, Mei C, Dong Z. miR-668 is induced via HIF-1 in ischemic acute kidney injury to repress MTP18 for mitochondrial dynamics and cell survival. Journal of Clinical Investigation 128: 5448-5464, 2018 (Highlighted by Editorial: JCI 128:5216-8; with news report).

d. Ma Z,Li L,Livingston MJ,Zhang D,Mi Q, Zhang M, Ding HF, Huo Y, Mei C, Dong Z. p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. Journal of Clinical Investigation 130(9):5011-5026, 2020 (news report).

5. Discover an alternative splice form of check-point kinase 1 that regulates cell cycle and DNA damage checkpoints, delineate the differential PKCδ signaling pathways in malignant and normal tissues, discover the novel interaction between Intu and STAT1 in the regulation of cell death and cilia in kidney injury, and reported the first evidence of stress granules in kidney disease.

Representative Original Publications:

a. Pabla N, Bhatt K, Dong Z. Chk1-S is a splice variant and endogenous inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints. Proceedings of National Academy of Sciences (USA) 109: 197-202, 2012. (news report)

b. Pabla N, Dong G, Jiang M, Huang S, Kumar MV, Messing R, Dong Z. PKCd is a novel regulator of cisplatin nephrotoxicity and effective target for renoprotection during cancer therapy. Journal of Clinical Investigation 121: 2709-2722, 2011. (news report)

c. Wang S, Liu A, Wu G, Ding H, Huang S, Dong Z. The CPLANE protein Intu protects kidneys from ischemia-reperfusion injury by targeting STAT1 for degradation. Nature Communications 2018 Mar 26; 9(1):1234. (Highlighted by Commentary: Nat Rev Nephrol. 2018;14:354) d. Wang S, Kwon SH, Su Y, Dong Z. Stress granules are formed in renal proximal tubular cells during metabolic stress and ischemic injury for cell survival. Am J Physiol Renal Physiol. 2019;317:F116-F123.