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.

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National Heart, Lung, and Blood Institute
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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
Kang, Ju-Gyeong; Wang, Ping-yuan; Hwang, Paul M (2014) Cell-based measurements of mitochondrial function in human subjects. Methods Enzymol 542:209-21
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
Park, Joon-Young; Wang, Ping-Yuan; Matsumoto, Takumi et al. (2009) p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res 105:705-12, 11 p following 712
Biesecker, Leslie G; Mullikin, James C; Facio, Flavia M et al. (2009) The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicine. Genome Res 19:1665-74
Matsumoto, Takumi; Wang, Ping-Yuan; Ma, Wenzhe et al. (2009) Polo-like kinases mediate cell survival in mitochondrial dysfunction. Proc Natl Acad Sci U S A 106:14542-6
Finkel, Toren; Hwang, Paul M (2009) The Krebs cycle meets the cell cycle: mitochondria and the G1-S transition. Proc Natl Acad Sci U S A 106:11825-6
Fujimura, Yota; Hwang, Paul M; Trout Iii, Hugh et al. (2008) Increased peripheral benzodiazepine receptors in arterial plaque of patients with atherosclerosis: an autoradiographic study with [(3)H]PK 11195. Atherosclerosis 201:108-11