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Zheng Dong, Ph.D.
zdong@mcg.edu

Telephone: 706.721.2825
Fax: 706.721.6120
Room: CB-2917A

Professor, Department of Cellular Biology and Anatomy

Departmental Director of Graduate Studies

Education and Training:


1989     B.Sc.,     Microbiology, Fudan University, Shanghai, P.R. China

1994     Ph.D.,     Physiology, Shanghai Institute of Physiology, Chinese Academy of Sciences

1998     Postdoc  University of Texas Health Science Center at San Antonio

 

Research Experience:

1994     Postdoctoral Fellow, Department of Pathology, UT Health Science Center

1998     Research Instructor, Department of Pathology, UT Health Science Center

1999     Assistant Professor, Department of Pathology, UT Health Science Center

2002-    Associate Professor, Department of Cellular Biology and Anatomy, MCG

2004-    Research Physiologist, VA Medical Center at Augusta, GA

2007     Professor, Department of Cellular Biology and Anatomy, MCG

 

 Honors and Awards :
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, VA

2005   Distinguished Faculty Award (Basic Science)  School of Medicine, MCG

2005   Distinguished Research Award                  School of Graduate Studies, MCG

Extramural Grant Support:

National Institutes of Health

Department of Veteran’s Affairs

American Heart Association

Research Interest:

Cell injury and adaptation under hypoxic/ischemic stress: Lack of oxygen, i.e. hypoxia, is a key determinant of several important pathogenic processes.  Solid tumors adapt to hypoxic microenvironments by selecting for death resistance, which confers poor prognosis.  On the other hand, hypoxia leads to massive cell death in ischemic diseases including stroke, myocardial infarction and acute renal failure.  The objective of our research is to understand why some cells die during hypoxia whereas others can adapt to the stress and survive.  We have shown that, under hypoxia, cells are injured due to ATP-depletion and death by necrosis ensues.  Necrotic death of the hypoxic cells can be prevented by glycine, a small amino acid.  However, glycine is unable to rescue the cells permanently, and after re-oxygenation, these cells undergo apoptosis.  Apoptosis of reoxygenated cells is mediated by the mitochondrial pathway involving the proapoptotic molecule Bax, cytochrome c, and caspases.  Our current studies aim at further understanding of the apoptotic mechanisms responsible for hypoxic injury, the molecular basis of glycine cyto-protection and the regulation of cell injury related genes by hypoxia.  These studies are expected to gain insights into the cell injury and adaptation mechanisms activated by hypoxia-reoxygenation, and provide a theoretical basis for developing novel strategies to reduce tissue pathology caused by hypoxia/ischemia.

 Molecular signaling of cisplatin-induced nephrotoxicity

Cisplatin, a widely used chemotherapy drug, induces renal cell injury and nephrotoxicity, which limits its therapeutic efficacy.  We have demonstrated a role of p53 in renal cell apoptosis during cisplatin

treatment.  Our recent work

further shows that PUMA-a, a

unique BH3-only Bcl-2 protein,

is induced by p53 under the

experimental condition.  Upon

induction, PUMA accumulates

in mitochondria and

antagonizes Bcl-XL, resulting

in Bax activation, cytochrome

c release and apoptosis. 

Future studies aim at the

identification of the signaling

pathways and molecules that

regulate p53 and PUMA.  Work in

this direction may provide insights into

the cellular and molecular basis of cisplatin nephrotoxicity, and identify renal protective strategies to enhance the efficacy of the cancer therapy drug. 

 Key Words:

Apoptosis; Mitochondria; Cell injury and death; Adaptation; Gene regulation; Hypoxia;  Cisplatin; Chemotherapy; Chemoprotection; Acute renal failure

 Techniques:

Molecular cloning; promoter analysis; Northern, Southern & Western blot; Immunoprecipitation, Immunocytochemistry; Immunofluorescence; Cell death (apoptosis/necrosis) detection.

Recent Representative Publications:

Wei Q, Alam M, Wang M, Yu F, Dong Z. Bid Activation in Kidney Cells Following ATP Depletion in vitro and Ischemia in vivo.  American Journal of Physiology  286(4):F803-809, 2004.

Dong Z, Wang J.  Hypoxia Selection of Death Resistance Cells: a role for Bcl-XL. Journal of Biological Chemistry 279(10): 9215-9221, 2004.

Wang J, Wei Q, Wang CY, Hill WD, Hess DC, Dong Z.  Minocycline up-regulates Bcl-2 and protects against cell death in the mitochondria.  Journal of Biological Chemistry 279:19948-19954, 2004.

Wei Q, Wang J, Wang M, Yu F, Dong Z. Inhibition of Apoptosis by Zn2+ in Renal Tubular Cells Following ATP-depletion. American Journal of Physiology 287: F492-500, 2004.

Jiang M, Yi  X, Hsu S, Wang C, Dong Z . Role of p53 in cisplatin-induced tubular cell apoptosis: dependent on p53 transcriptional activity.  American Journal of Physiology: 287: 1140-1147, 2004.

Brooks C, Ketsawatsomkron P, Sui Y, Wang C, Yu F, Dong Z. Acidic pH Inhibits ATP depletion-induced Tubular Cell Apoptosis by Blocking Caspase-9 Activation in Apoptosome. American Journal of Physiology 289(2):F410-419, 2005.

Wei Q, Yin X, Wang M, Dong Z. Amelioration of Ischemic Renal Injury and Renal Failure in Bid-deficient Mice. American Journal of Physiology 290: F35-F42, 2006.

Wang J, Biju M, Wang M, Haase V, Dong Z. Cytoprotective effects of hypoxia against cisplatin-induced tubular cell apoptosis:     Involvement of Mitochondrial Inhibition and p53 Suppression. Journal of American Society of Nephrology 17(7):1875-1885, 2006

Jiang M, Wei Q, Wang J, Du Q, Yu J, Zhang L, Dong Z. Regulation of PUMA-a by p53 in Cisplatin-induced renal cell apoptosis.  Oncogene 25: 4056-4066, 2006.

Wang J, Pabla N, Wang C, Wang W, Schoenlein PV, Dong Z.  Caspase-mediated cleavage of ATM during cisplatin-induced tubular cell apoptosis: inactivation of its kinase activity towards p53.  American Journal of Physiology, 291: F1300-F1307, 2006.

Dong Z, Saikumar P, Weinberg J, Venkatachalam M.  Calcium in Cell Injury and Death.  Annual Reviews of Pathology 1:405-434, 2006.

Brooks C, Wang J, Dong Z. Characterization of Cell Clones Isolated from Hypoxia-selected Renal Proximal Tubular cells.  American Journal of Physiology, 292(1):F243-52, 2007.

Jiang M, Wei Q, Pabla N, Dong G, Wang C, Yang T, Smith S, Dong Z.  Effects of hydroxyl radical scavenging on cisplatin-induced p53 activation, tubular cell apoptosis and nephrotoxicity. Biochemical Pharmacology, 73(9):1499-510, 2007.

 Jiang M, Pabla N, Murphy RF, Yang T, Yin XM, Degenhardt K, White E, .Dong Z. Nutlin-3 Protects Kidney Cells during Cisplatin Therapy by Suppressing Bax/Bak activation. Journal of Biological Chemistry, 282(4):2636-45, 2007.

Wei Q, Dong G, Franklin J, Dong Z.  The pathological role of Bax in cisplatin nephrotoxicity.  Kidney International 72(1):53-62. 2007.

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.

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Cellular Biology and Anatomy
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Please email comments, suggestions or questions to:
Nan Eaton,
neaton@mcg.edu

July 10, 2007