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 hypothesize that these two independent observations may share common mechanisms 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 insights from human studies that may assist in the development of new strategies for preventing cancer and improving cardiovascular health.
| Park, Ji-Hoon; Li, Jie; Starost, Matthew F et al. (2018) Mouse Homolog of the Human TP53 R337H Mutation Reveals Its Role in Tumorigenesis. Cancer Res 78:5375-5383 |
| 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 |
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