A developing area of interest to our laboratory is investigating novel mechanisms of mitochondrial regulation that may be important for cardiovascular function. We have recently shown that the tumor suppressor gene p53 profoundly affects exercise capacity in mice, and we have identified the mediator gene as an assembly factor of the cytochrome c oxidase complex. This finding may offer a molecular explanation for some of our previous observations of p53 dependent oxidant generation and heart failure by chemotherapeutic agents. We are now initiating studies to translate some of these basic observations to human studies.? ? Our laboratory is also molecularly dissecting easily accessible human cells important for atherosclerosis to gain new insights into the disease process. Using unbiased approaches, we have identified monocyte and macrophage transcription factors as a reactive disease markers and mediators of disease. Studies are underway to elucidate the molecular mechanisms of candidate genes in pathogenesis using mouse and human model systems.
| 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 |
| Zhuang, Jie; Kamp, William M; Li, Jie et al. (2016) Forkhead Box O3A (FOXO3) and the Mitochondrial Disulfide Relay Carrier (CHCHD4) Regulate p53 Protein Nuclear Activity in Response to Exercise. J Biol Chem 291:24819-24827 |
| 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 |
| 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 |
| Fields, Jerad; Hanisch, Jesse J; Choi, Jeong W et al. (2007) How does p53 regulate mitochondrial respiration? IUBMB Life 59:682-4 |
| Ma, Wenzhe; Sung, Ho Joong; Park, Joon Y et al. (2007) A pivotal role for p53: balancing aerobic respiration and glycolysis. J Bioenerg Biomembr 39:243-6 |
| Matsumoto, Takumi; Hwang, Paul M (2007) Resizing the genomic regulation of restenosis. Circ Res 100:1537-9 |
| Liu, Hongjun; Fergusson, Maria M; Castilho, Rogerio M et al. (2007) Augmented Wnt signaling in a mammalian model of accelerated aging. Science 317:803-6 |
| Kang, Ju-Gyeong; Patino, Willmar D; Matoba, Satoaki et al. (2006) Genomic analysis of circulating cells: a window into atherosclerosis. Trends Cardiovasc Med 16:163-8 |
| Das, Hiranmoy; Kumar, Ajay; Lin, Zhiyong et al. (2006) Kruppel-like factor 2 (KLF2) regulates proinflammatory activation of monocytes. Proc Natl Acad Sci U S A 103:6653-8 |
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