Regents' Professor (part time), Leon H. Charbonnier Endowed Chair
Department of Cellular Biology and Anatomy
Senior Research Career Scientist, Director of Research Development
Charlie Norwood VA Medical Center
Office: R&E Building, CB1124
Phone: 706-721-2825
Fax: 706-721-6120
Email: zdong@augusta.edu
Lab Personnel:
Qingqing Wei, PhD, Asst Professor
Man J. Livingston, MD/PhD, Asst Res Scientist
Shixuan Wang, MD/PhD, Asst Res Scientist
Zhengwei Ma, MD/PhD, Senior Research Associate
Guie Dong, Senior Research Associate
Siyao Li, MD, Visiting Researcher
Lu Wen, MD, Visiting Researcher
Xiaoru Hu, MD, Visiting Researcher
| 1985-1989 B.Sc. | Microbiology, Fudan University, Shanghai, P.R. China | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 1989-1994 PhD | Physiology, Shanghai Institute of Physiology, Chinese Academy of Sciences | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 1994-1998 | University of Texas Health Science Center (UTHSC) at San Antonio | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2000 | Lyndon B. Johnson Research Award | American Heart Association | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2001 | Carl W. Gottschalk Scholar Award | American Society of Nephrology | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2001 | Patricia W. Robinson Young Investigator | National Kidney Foundation | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2004 | Career Development Award | VISN 7, Department of Veterans Affairs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2005 | Distinguished Faculty Award (Basic Science) | Medical College of Georgia, MCG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2005 | Distinguished Research Award | School of Graduate Studies, MCG | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2008 | Research Career Scientist Award | Department of Veterans Affairs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2011 | Regents’ Professorship | University System of Georgia | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2013 | Senior Research Career Scientist | Department of Veterans Affairs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2016 | Leon H. Charbonnier Endowed Chair | Augusta University | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2017 | Distinguished Faculty Award in Basic Science | Augusta University | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 2020 | Senior Research Career Scientist Award | Department of Veterans Affairs | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
American Journal of Physiology - Renal Physiology (Associate Editor 2020-present)
Kidney Diseases (Associate Editor 2019-present)
Journal of American Society of Nephology (Guest Associate Editor 2014, 2016, 2017)
Seminar in Nephrology (Guest Editor 2014)
Kidney International (2010-present)
Journal of American Society of Nephrology (2015-present)
American Journal of Physiology-Renal Physiology (2011-2020)
American Journal of Physiology-Cell Physiology (2018-present)
and others
1) Essentials of Apoptosis: A Guide for Basic and Clinical Research
Editors: Xiao-Ming Yin and Zheng Dong
1st edition, Humana Press, 259 pages.
ISBN: 978-1-59259-361-3, 2003
2nd edition, Humana Press, 707 pages.
ISBN: 978-1-60327-380-0, 2009
http://www.springer.com/us/book/9781603273800
2) Cell Death in Biology and Diseases
Series Editor: Xiao-Ming Yin and Zheng Dong
Publisher: Springer
| NIH: | Chartered Member | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2012-2016 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Ad hoc member: | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2006.10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2007.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2008.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2010.10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2011.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PBKD Study Section 2011.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PCD Study Section 2002.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| CSD Study Section 2006.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-G 02, 2009.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-A 58 2009.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-K11 2009.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-G 03, 2009.9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-G11, 2010.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-A 05, 2011.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 OBT-Z 50, 2013.3 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZDK1 GRB-N z(J6), 2013.9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Botanical Dietary Supplement Research Centers (P50), 2014.10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NCI Special panel ZCA1 RPRB-M (M5) 2016.4 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NCI Special panel ZCA1 SRB-1 (J1) R 2016.11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-J (03) 2016.12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-P (91) S 2017.01 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-P (02) M 2017.04 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 IDM-C 50 2017.07 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-P (04) 2017.10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| NCI Special panel ZCA1 SRB-A (M1) S 2018.02 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-L (55) 2018.06 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZRG1 DKUS-G (03) 2020.03 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Special panel ZDK1 GRB-M (M1) 2020.04 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| VA: | Career Development Award Program 2006.8 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2010.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2010.12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2011.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2011.12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2012.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2019.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| RDS/Promotions Review Committee 2019.5 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2019.12 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Merit Review Panel for Nephrology 2020.11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| DoD: | U.S. Army Research Program 2004.6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| EPSCoR IDeA Program 2006.7 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| PRCRP 2011 D-Kidney Cancer panel 2011.11 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Others: | Nebraska Research Initiative 2011.12, 2012.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| University of Toledo Intramural Program 2019.3; 2020.2 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| University of Texas Health Science Center at San Antonio 2019, 2020 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| China: | National Basic Research Program 2010.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 1000 Talents Program for Young Scholars 2012.11; 2014 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Changjiang Scholar Program 2013.5; 2015.5; 2016.7; 2017.9 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Outstanding Young Investigator Program 2012; 2015, 2016, 2018 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Chinese National Science Foundation 2013-present | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| France: | French National Research Agency 2015.4, 2016.4 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Germany: | German Research Foundation 2013.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Hong Kong: | Research Grant Council (RGC) of Hong Kong Panel Member: 2020-2022 Ad hoc: 2013.3; 2014.3, 2015.3, 2015.8, 2016.3, 2016.9, 2017.3, 2018.3 |
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| Netherland: | Dutch Cancer Society 2012.7 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Dutch Kidney Foundation 2018.6 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Poland: | National Science Centre 2013.3, 2017.3 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Romania: | Romanian National Council for Scientific Research 2011.11 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Singapore: | Biomedical Research Council Program 2004.2, 2007.5, 2009.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Switzerland: | Swiss National Science Foundation 2016.5 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| UK: | Cancer Research UK 2011.2, 2018.6 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Medical Research Council (MRC) 2011.10 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Yorkshire Cancer Foundation 2013.8 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Kidney Research UK 2013.1, 2014.1 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Research Interests
The long-term goal of our research is to delineate the mechanism of cell death, its protection, and subsequent regeneration during kidney injury and kidney repair. My current work is focused on mitochondria, metabolism, autophagy, and epigenetic regulation in disease conditions of acute kidney injury and diabetic kidney disease. As of February 1, 2021, we have published 290 full-length articles with a Google Scholar H-index of 76. The publications, including 215 original papers and 75 invited reviews and commentaries, have been cited more than 25,000 times, attesting the contribution to the field of kidney injury and repair in renal diseases and, cell death in general.
Contributions to Science
1. We have delineated 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. We 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. Our recent work further demonstrated a striking change of mitochondrial dynamics during cell injury and stress in diseases. We discovered a novel role of Bak in mitochondrial fragmentation and damage under cell stress and disease conditions. We further unveiled Bif-1 as a key regulator of mitochondrial inner membrane dynamics. These studies have been published in >40 research articles and have been cited for >5000 times. We 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. We have unveiled 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 >35 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).
Representative Original Publications:
a. Jiang M, Wei Q, Wang J, Du Q, Yu J, Zhang L, Dong Z. Regulation of PUMA-alpha by p53 in cisplatin-induced renal cell apoptosis. Oncogene 25:4056-66, 2006. 25:4056-66, 2006.
b.Pabla N, Huang S, Mi QS, Daniel R, Dong Z. ATR-Chk2 signaling in p53 activation and DNA damage response during cisplatin-induced apoptosis. Journal of Biological Chemistry 283: 6572 – 6583, 2008. PMID: 18162465 (Highlighted by Faculty 1000).
c. 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. PMCID: 3060494.
d. 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).
3. We have demonstrated the first evidence of autophagy in acute kidney injury and have further established its role in kidney injury and repair. This line of work has been 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 >30 research articles and have been cited for ~3000 times. , We 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. We have reported the first evidence of microRNA and DNA methylation as epigenetic mechanisms in ischemic and cisplatin nephrotoxic kidney injury. We have subsequently delineated the regulation of several specific microRNAs in kidney injury, protection, and repair. These studies, published in >25 research articles, have gained new insights into the pathogenesis of acute kidney injury and recovery, and have suggested novel therapeutic strategies by targeting epigenetics. We 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. We have delineated the differential PKCδ signaling pathways in malignant and normal tissues suggesting an effective approach for kidney protection during cisplatin chemotherapy. We have discovered a new alternatively spliced checkpoint kinase-1 (named Chk1-S) as a novel regulator of cell cycle and DNA damage response. Our latest work has discovered the novel interaction between Intu and STAT1 in the regulation of cell death and cilia in kidney injury.
Representative Original Publications:
a. Pabla N, Dong G, Jiang M, Huang S, Kumar MV, Messing R, Dong Z. PKCδ is a novel regulator of cisplatin nephrotoxicity and effective target for renoprotection during cancer therapy. Journal of Clinical Investigation 121: 2709-2722, 2011. PMCID: PMC3223835 (news report).
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. PMCID: PMC3252905 (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. PMCID: PMC5964315.
Confocal image of mitochondria. In control cells, mitochondria are elongated and filamentous. After injury, mitochondria are fragmented into short rods or spheres. The morphological change contributes to mitochondrial damage and apoptosis (Brooks…Dong. PNAS 104: 11649-11654, 2007. Journal of Clinical Investigation 119:1275-85, 2009).
Ovarian cancer xenografts were established in nude mice, which were then treated with
cisplatin with or without Rottlerin, a PKCδ inhibitor. In this and other tumor models,
Rottlerin and relevant protect protect kidneys and enhance cancer therapy effect during
cisplatin treatment. (Pabla…Dong. Journal of Clinical Investigation 121: 2709-2722, 20112011).
miR-668 is induced via HIF-1 in ischemic acute kidney injury to repress MTP18 for
mitochondrial dynamics and cell survival. Wei…Dong. Journal of Clinical Investigation 128: 5448-5464, 2018
p53/microRNA-214/ULK1 axis impairs renal tubular autophagy in diabetic kidney disease. Ma…Dong. Journal of Clinical Investigation 130(9):5011-5026, 2020
Approaches:
Gene cloning, transfection, expression, knockout (antisense and RNAi), promoter assay, genotyping, Northern/Southern blot, microRNA analysis, immunoblotting, immunoprecipitation, immunofluorescence, immunohistochemistry and light/fluorescence/confocal microscopy. In vitro and in vivo experimental models, germline and tissue specific gene knockout mice.
Grant Support:
National Institutes of Health; Department of Veterans Affairs
Representative Publications (2017-2021):
A. Original Studies
1. * Hao J, Wei Q, Mei S, Li L, Su Y, Mei C, Dong Z. MicroRNA-17-5p Is Induced via p53 to Protect against Renal Ischemia-Reperfusion
Injury by Targeting Death Receptor 6. Kidney International, 91, 106–118, 2017.
2. * Zhang D, Pan J, Xiang X, Liu Y, Dong G, Livingston MJ, Chen JK, Yin XM, Dong Z. Protein Kinase Cδ Suppresses Autophagy to Induce Kidney Cell Apoptosis in Cisplatin
Nephrotoxicity. Journal of American Society of Nephrology 28(4):1131-1144, 2017. (Selected by Autophagy for commentary).
3. * Zhou X, Zhang W, Yao Q, Zhang H, Dong G, Zhang M, Liu Y, Chen JK, Dong Z. Exosome production and its regulation of EGFR during wound healing in renal tubular
cells. Am J Physiol Renal Physiol. 312(6):F963-F970. 2017.
4. * Hao J, Lou Q, Wei Q, Mei S, Li L, Mi Q, Mei C, Dong Z. MicroRNA-375 Is Induced in Cisplatin Nephrotoxicity to Repress Hepatocyte Nuclear
Factor 1-beta. Journal of Biological Chemistry, 292:4571-4582, 2017.
5. * Yi M, Zhang L, Liu Y, Livingston MJ, Chen JK, Nahman NS Jr, Liu F, Dong Z. Autophagy is activated to protect against podocyte injury in adriamycin-induced
nephropathy. Am J Physiol Renal Physiol. 313(1):F74-F84, 2017.
6. * Mei S, Li L, Wei Q, Hao J, Su Y, Mei C, Dong Z. Double knockout of Bax and Bak from kidney proximal tubules reduces unilateral urethral
obstruction associated apoptosis and renal interstitial fibrosis. Scientific Reports. 2017 Mar 20;7:44892. doi: 10.1038/srep44892.
7. * Zhang W, Zhou X, Yao Q, Liu Y, Zhang H, Dong Z. HIF-1-mediated production of exosomes during hypoxia is protective in renal tubular
cells. Am J Physiol Renal Physiol. 2017 313(4):F906-F913.
8. *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 2017, 92(5):1194-1205.
9. * Tang C, Wang H, Yan M, Zhu S, Liu J, Liu Z, He L, Tan J, Liu Y, Liy H, Sun L,
Duan S, Peng Y, Liu F, Yin X, Zhang Z, Dong Z. PINK1-Parkin pathway of mitophagy is activated to protect against renal ischemia/reperfusion
injury. Autophagy 2018;14(5):880-897.
10. * Liu J, Livingston M, Dong G, Tang C, Su Y, Wu G, Yin X, Dong Z. Histone Deacetylase Inhibitors Protect Against Cisplatin-induced Acute Kidney Injury
by Activating Autophagy in Proximal Tubular Cells. Cell Death & Disease. 2018 Feb 23;9(3):322. doi: 10.1038/s41419-018-0374-7.
11. * Sun L, Liu J, Yuan Y, Zhang X, Dong Z. Protective effect of the BET protein inhibitor JQ1 in cisplatin-induced nephrotoxicity.
Am J Physiol Renal Physiol. 2018 Sep 1;315(3):F469-F478.
12. * Li F, Liu Z, Tang C, Cai J, Dong Z. FGF21 is induced in cisplatin nephrotoxicity
to protect against kidney tubular cell injury. FASEB J 2018, 32(6):3423-3433.
13. * Wang S, Liu A, Wu G, Ding H, Huang S, Nahman 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. doi: 10.1038/s41467-018-03628-8.
14. * Ma Z, Wei Q, Zhang M, Chen JK, Dong Z. Dicer deficiency in proximal tubules exacerbates renal injury and tubulointerstitial
fibrosis and upregulates Smad2/3. Am J Physiol Renal Physiol. 2018 Dec 1;315(6):F1822-F1832.
15. * Lou Q, Hu Y, Ma Y, Dong Z. RNA interference may suppresses stress granule formation by preventing Argonaute
2 recruitment. Am J Physiol Cell Physiol. 2019, 316(1):C81-C91.
16. * Wang Y, Tang C, Cai J, Chen G, Zhang D, Zhang Z, Dong Z. PINK1/Parkin-mediated mitophagy is activated in cisplatin nephrotoxicity to protect
against kidney injury. Cell Death Dis. 2018 Nov 1;9(11):1113.
17. * Shu S, Zhu J, Liu Z, Cai J, Tang C, Dong Z. Endoplasmic reticulum stress is activated in post-ischemic kidneys to promote chronic
kidney disease. EBioMedicine 37: 269-280. 2018.
18. * 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 2018 Dec 1;128(12):5448–5464.
19. * Chen G, Chen H, Ren S, Xia M, Zhu J, Liu Y, Zhang L, Tang L, Sun L, Liu H, Dong Z. Aberrant DNA methylation of mTOR pathway genes promotes inflammatory activation
of immune cells in diabetic kidney disease. Kidney Int. 2019 Aug;96(2):409-420.
20. * Wei Q, Su J, Dong G, Zhang M, Huo Y, Dong Z. Glycolysis inhibitors suppress renal interstitial fibrosis via divergent effects
on fibroblasts and tubular cells. Am J Physiol Renal Physiol. 2019 Jun 1;316(6):F1162-F1172.
21. * 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 Jul 1;317(1):F116-F123.
22. * Fu Y, Cai J, Li F, Liu Z, Shu S, Wang Y, Liu Y, Tang C, Dong Z. Chronic effects of repeated low dose cisplatin treatment in mouse kidneys and renal
tubular cells. Am J Physiol Renal Physiol. 2019 Dec 1;317(6):F1582-F1592.
23. * 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 2019 Dec;15(12):2142-2162.
24. * 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 2019 Jul;30(7):1174-1191.
25. * Cai J, Liu Z, Huang X, Shu S, Hu X, Zheng M, Tang C, Liu Y, Chen G, Sun L, Liu
H, Liu F, Cheng J, Dong Z. The deacetylase sirtuin 6 protects against kidney fibrosis by epigenetically blocking
β-catenin target gene expression. Kidney Int. 2020 Jan;97:106-118 (with editorial
commentary by Gewin L. Kidney International. 2020;97:27-29).
26. * Yan Y, Ma Z, Zhu J, Zeng M, Liu H, Dong Z. miR-214 represses Mitofusin-2 to promote renal tubular apoptosis in ischemic acute
kidney injury. Am J Physiol Renal Physiol. 2020 Apr 1;318(4):F878-F887.
27. * Liu Y, Fu Y, Liu Z, Shu S, Wang Y, Cai J, Tang C, Dong Z. Irisin is induced in renal ischemia-reperfusion to protect against tubular cell
injury via suppressing p53. Biochim Biophys Acta Mol Basis Dis. 2020 Jul 1;1866(7):165792.
28. * Song Z, Zhu J, Wei Q, Dong G, Dong Z. Canagliflozin reduces cisplatin uptake and activates Akt to protect against cisplatin-induced
nephrotoxicity. Am J Physiol Renal Physiol. 2020 Apr 1;318(4):F1041-F1052.
29. * Wang Y, Zhu J, Liu Z, Shu S, Fu Y, Liu Y, Cai J, Tang C, Liu Y, Yin X, Dong Z. The PINK1/PARK2/optineurin pathway of mitophagy is activated for protection in septic
acute kidney injury. Redox Biology. 2020 Oct 23;38:101767.
30. * Zhu J, Zeng C, Zhang L, Shu S, Liu Y, Chen G, Liu H, Liu Y, Dong Z. Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio in Predicting
Adverse Outcomes of Acute Kidney Injury in Hospitalized Patients. Kidney Dis (Basel). 2020 Sep;6(5):371-381.
31. * Wen J, Ma Z, Livingston MJ, Zhang W, Yuan Y, Guo C, Liu Y, Fu P, Dong Z. Decreased secretion and profibrotic activity of tubular exosomes in diabetic kidney
disease. Am J Physiol Renal Physiol. 2020 Oct 1;319(4):F664-F673.
32. * Li F, Sun A, Cheng G, Liu D, Xiao J, Zhao Z, Dong Z. Compound C Protects Against Cisplatin-Induced Nephrotoxicity Through Pleiotropic
Effects. Front Physiol. 2020, 23;11:614244.
33. * Zhu J, Zhang G, Song Z, Xiang X, Shu S, Liu Z, Yang D, Wei Q, Dong Z. PKCδ mediates kidney tubular injury in renal cold-storage transplantation. Journal of American Society of Nephrology 2020 May;31(5):1050-1065.
34. * Liu Z, Yang D, Gao J, Xiang X, Hu X, Li S, Wu W, Cai J, Tang C, Zhang D, Dong Z. Discovery and validation of miR-452 as an effective biomarker for acute kidney injury
in sepsis. Theranostics. 2020 Oct 25;10(26):11963-11975.
35. * 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 2020;130(9):5011-5026.
36. * Liu Z, Tang C, He L, Yang D, Cai J, Zhu J, Shu S, Liu Y, Yin L, Chen G, Liu
Y, Zhang D, Dong Z. The negative feedback loop of NF-kB/miR-376b/NFKBIZ in septic acute kidney injury.
JCI Insight 2020 Dec 17;5(24):e142272.
37. * Zeng M, Wen J, Ma Z, Xiao L, Liu Y, Kwon S, Liu Y, Dong Z. FOXO1-mediated Downregulation of RAB27B Leads to Decreased Exosome Secretion in
Diabetic Kidneys. Diabetes. 2021 Feb 17:db201108.
B. Invited Reviews/ Commentaries
1. * He L, Wei Q, Liu J, Yi M, Liu Y, Liu H, Sun L, Peng Y, Liu F, Venkatachalam MA,
Dong Z. AKI on CKD: heightened injury, suppressed repair, and the underlying mechanisms.
Kidney International 92(5):1071-1083. 2017.
2. Hypoxia, HIF, and Associated Signaling Networks in Chronic Kidney Disease. Int J Mol Sci. 2017 Apr 30;18(5). pii: E0950. doi: 10.3390/ijms18050950. PMCUD: PMC5454863.
3. *Li F, Livingston MJ, Dong Z. Protection of kidneys by magnesium in cisplatin chemotherapy: a fight between two
metals. Am J Physiol Renal Physiol. 2017, 313(4):F955-F956.
4. *Zhang D, Xu X, Dong Z. PKCδ contributes to nephrotoxicity during cisplatin chemotherapy by suppressing
autophagy. Autophagy 13(3):631-632, 2017.
5. * Yang D, Livingston MJ, Liu Z, Dong G, Zhang M, Chen JK, Dong Z. Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic
potential. Cell Mol Life Sci. 75(4):669-688, 2018.
6. * Liu J, Dong Z. Neutrophil extracellular traps in ischemic AKI: new way to kill. Kidney International 93(2):303-305, 2018.
7. * Yan M, Shu S, Guo C, Tang C, Dong Z. Endoplasmic Reticulum Stress in Ischemic and Nephrotoxic Acute Kidney Injury. Ann Med. 2018 Aug;50(5):381-390.
8. * Fu Y, Tang C, Cai J, Chen G, Zhang D, Dong Z. Rodent models of AKI-CKD transition. Am J Physiol Renal Physiol. 2018;315(4):F1098-F1106.
9. * Tang C, Ma Z, Zhu J, Liu Z, Liu Y, Liu Y, Cai J, Dong Z. P53 in kidney injury and repair: Mechanism and therapeutic potentials. Pharmacol & Therapeutics. 2019 Mar;195:5-12.
10. * Xiang X, Guo C, Tang C, Cai J, Dong Z. Epigenetic Regulation in Kidney Toxicity: Insights From Cisplatin Nephrotoxicity.
Seminars in Nephrology. 2019 Mar;39(2):152-158.
11. * Guo C, Dong G, Liang X, Dong Z. Epigenetic regulation in kidney injury and repair: mechanisms and therapeutic implications.
Nature Reviews Nephrology 2019, 15(4):220-239.
12. * Shu S, Wang Y, Zheng M, Liu Z, Cai J, Tang C, Dong Z. Hypoxia and Hypoxia-Inducible Factors in Kidney Injury and Repair. Cells. 2019 Feb 28;8(3). pii: E207.
13. * Liu Z, Wang Y, Shu S, Cai J, Tang C, Dong Z. Non-coding RNAs in kidney injury and repair. Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C177-C188.
14. * Zhao XC, Livingston MJ, Liang XL, Dong Z. Cell Apoptosis and Autophagy in Renal Fibrosis. Adv Exp Med Biol. 2019;1165:557-584.
15. * Wang Y, Cai J, Tang C, Dong Z. Mitophagy in Acute Kidney Injury and Kidney Repair. Cells. 2020 Feb 1;9(2). pii: E338. doi: 10.3390/cells9020338.
16. Edelstein C, Venkatachalam MA, Dong Z. Autophagy inhibition by chloroquine and hydroxychloroquine could adversely affect
acute kidney injury and other organ injury in critically ill patients with COVID-19.
Kidney International. 2020 Jul; 98(1): 234–235.
17. * Tang C, Livingston M, Liu Z, Dong Z. Autophagy in kidney homeostasis and health and disease. Nature Reviews Nephrology 16(9):489-508, 2020.
18. * Wang S, Dong Z. Is autophagy the culprit of cystogenesis in polycystic kidney disease? EBioMedicine. 2020 Nov; 61:103043.
19. * Wang Y, Liu Z, Shu S, Cai J, Tang C, Dong Z. AMPK/mTOR Signaling in Autophagy Regulation During Cisplatin-Induced Acute Kidney
Injury. Front Physiol. 2020 Dec 17;11:619730.
20. * Wei Q, Dong Z. The yin and yang of retinoic acid signaling in kidney diseases. J Clin Invest. 2020 Oct 1;130(10):5124-5126.
21. * Li S, Wen L, Hu X, Wei Q, Dong Z. HIF in Nephrotoxicity during Cisplatin Chemotherapy: Regulation, Function and Therapeutic
Potential. Cancers (Basel). 2021 Jan 7;13(2):180.
22. * Tang C, Cai J, Yin X, Weinberg JM, Venkatachalam MA, Dong Z. Mitochondrial quality control in kidney injury and repair. Nature Reviews Nephrology 2020 Nov 24. doi: 10.1038/s41581-020-00369-0. Online ahead of print.
