We have shown that p53 balances the energy generated by respiration and glycolysis and promotes aerobic metabolism through it positive regulation of mitochondrial function. An interesting effect of this biological mechanism is that mice deficient in p53 display profound deficiencies in aerobic exercise capacity. Given the strong inverse relationship between exercise capacity and cancer incidence in large epidemiologic studies, we are characterizing the regulation of mitochondrial function by p53 as a tumor suppressor and the relation between cardiovascular exercise capacity and tumorigenesis using mouse models and human studies. Specifically, 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 research is to derive basic insights that may assist in the development of new strategies for preventing cancer and improving cardiovascular fitness.

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2011
Total Cost
$814,792
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
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Wang, Ping-Yuan; Li, Jie; Walcott, Farzana L et al. (2017) Inhibiting mitochondrial respiration prevents cancer in a mouse model of Li-Fraumeni syndrome. J Clin Invest 127:132-136
Kamp, William M; Wang, Ping-Yuan; Hwang, Paul M (2016) TP53 mutation, mitochondria and cancer. Curr Opin Genet Dev 38:16-22
Bouchard, Claude; Antunes-Correa, Ligia M; Ashley, Euan A et al. (2015) Personalized preventive medicine: genetics and the response to regular exercise in preventive interventions. Prog Cardiovasc Dis 57:337-46
Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M (2014) Cell-based measurements of mitochondrial function in human subjects. Methods Enzymol 542:209-21
Zhuang, Jie; Wang, Ping-yuan; Huang, Xinglu et al. (2013) Mitochondrial disulfide relay mediates translocation of p53 and partitions its subcellular activity. Proc Natl Acad Sci U S A 110:17356-61
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

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