We have shown that p53 promotes aerobic metabolism through its positive regulation of mitochondrial respiration. p53 null mice, a model of de novo tumorigenesis, display profound deficiencies in aerobic exercise capacity. Remarkably, the promotion of exercise capacity by a tumor suppressor gene in a mouse model parallels the human epidemiologic observation of a strong inverse relationship between exercise capacity and cancer incidence. We believe that these two independent observations may share a common mechanism for tumor suppression, therefore, we are investigating the regulation of mitochondrial function by p53 using in vitro and in vivo models. Additionally, we are studying cardiovascular and metabolic functions in individuals with Li-Fraumeni syndrome, a premature cancer syndrome caused by germline mutations in the p53 gene. The goal of this work is to derive basic insights that may assist in the development of new strategies for preventing cancer and improving cardiovascular health.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2013
Total Cost
$995,492
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
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Zip Code
Kamp, William M; Wang, Ping-Yuan; Hwang, Paul M (2016) TP53 mutation, mitochondria and cancer. Curr Opin Genet Dev 38:16-22
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Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M (2014) Cell-based measurements of mitochondrial function in human subjects. Methods Enzymol 542:209-21
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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; Wang, Ping-yuan et al. (2010) Mitochondrial respiration protects against oxygen-associated DNA damage. Nat Commun 1:5

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