Our previous studies have suggested that mitochondrial dysfunction causes oxidative genomic DNA damage and contributes to tumorigenesis. A major contributing factor is ambient oxygen which is the essential substrate for reactive oxygen species generation that can cause biological damage. Environmental and genetic methods will be used to modulate redox homeostasis and to determine their effect on energy metabolism, tumorigenesis, and cardiovascular disease. We are examining adaptive mechanisms by which cells of neoplastic or cardiovascular origin survive under oxidative or other toxic stress conditions.

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7
Fiscal Year
2016
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U.S. National Heart Lung and Blood Inst
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Chen, Jichun; Kang, Ju-Gyeong; Keyvanfar, Keyvan et al. (2016) Long-term adaptation to hypoxia preserves hematopoietic stem cell function. Exp Hematol :
Park, Ji-Hoon; Zhuang, Jie; Li, Jie et al. (2016) p53 as guardian of the mitochondrial genome. FEBS Lett 590:924-34
Zhuang, Jie; Kamp, William M; Li, Jie et al. (2016) Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise. J Biol Chem 291:24819-24827
Li, Jie; Ma, Wenzhe; Wang, Ping-yuan et al. (2014) Polo-like kinase 2 activates an antioxidant pathway to promote the survival of cells with mitochondrial dysfunction. Free Radic Biol Med 73:270-7
Wang, Ping-Yuan; Ma, Wenzhe; Park, Joon-Young et al. (2013) Increased oxidative metabolism in the Li-Fraumeni syndrome. N Engl J Med 368:1027-32
Zhuang, Jie; Ma, Wenzhe; Lago, Cory U et al. (2012) Metabolic regulation of oxygen and redox homeostasis by p53: lessons from evolutionary biology? Free Radic Biol Med 53:1279-85
Mai, Phuong L; Malkin, David; Garber, Judy E et al. (2012) Li-Fraumeni syndrome: report of a clinical research workshop and creation of a research consortium. Cancer Genet 205:479-87
Wang, Ping-Yuan; Zhuang, Jie; Hwang, Paul M (2012) p53: exercise capacity and metabolism. Curr Opin Oncol 24:76-82
Lago, Cory U; Sung, Ho Joong; Ma, Wenzhe et al. (2011) p53, aerobic metabolism, and cancer. Antioxid Redox Signal 15:1739-48
Sung, Ho Joong; Ma, Wenzhe; Starost, Matthew F et al. (2011) Ambient oxygen promotes tumorigenesis. PLoS One 6:e19785

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