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.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2012
Total Cost
$668,168
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
Zip Code
Park, Ji-Hoon; Zhuang, Jie; Li, Jie et al. (2016) p53 as guardian of the mitochondrial genome. FEBS Lett 590:924-34
Chen, Jichun; Kang, Ju-Gyeong; Keyvanfar, Keyvan et al. (2016) Long-term adaptation to hypoxia preserves hematopoietic stem cell function. Exp Hematol :
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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
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Sung, Ho Joong; Ma, Wenzhe; Wang, Ping-yuan et al. (2010) Mitochondrial respiration protects against oxygen-associated DNA damage. Nat Commun 1:5