Our current studies suggest mitochondrial dysfunction causes oxygen-associated genomic DNA damage. Because oxygen serves as an essential factor for oxidative stress, a cause of genomic instability, we have been examining the effect of modulating ambient oxygen on de novo tumorigenesis. We have found that decreasing the ambient oxygen exposure of p53 null mice causes a striking delay in tumorigenesis. We are now investigating this phenomenon in further detail. As hypoxia is known to affect the cardiovascular system, we are monitoring its effect on cardiovascular health for potential side-effects. These studies may provide insights into how modulation of ambient oxygen affects the course of tumorigenesis and have clinical implications.

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National Heart, Lung, and Blood Institute
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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
Sung, Ho Joong; Ma, Wenzhe; Starost, Matthew F et al. (2011) Ambient oxygen promotes tumorigenesis. PLoS One 6:e19785
Lago, Cory U; Sung, Ho Joong; Ma, Wenzhe et al. (2011) p53, aerobic metabolism, and cancer. Antioxid Redox Signal 15:1739-48

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