We are focusing on a novel pathway that regulates mitochondrial function and cardiovascular exercise capacity with implications for tumorigenesis. We have recently shown that the tumor suppressor gene p53 balances the energy generated by respiration and glycolysis and that this effect is primarily mediated through a p53 transcriptional target gene involved in cytochrome c oxidase complex assembly. Interestingly, mice deficient in p53 display profound deficiencies in aerobic exercise capacity revealing a new function for a well-studied gene mainly associated with cell cycle and genomic regulation. This finding also offers possible molecular explanations for some of our previous observations of p53 dependent oxidant generation and heart failure by chemotherapeutic agents. We are further characterizing our preliminary findings, and we are initiating studies to translate some of these basic observations to human studies.? ? Our laboratory is also examining easily accessible human cells important for atherosclerosis to gain new insights into this cardiovascular disease. Using unbiased approaches, we have identified monocyte and macrophage transcriptional regulators as reactive markers and mediators of disease. We are performing studies to determine their clinical utility as markers and to elucidate their role as disease mediators using patient samples and 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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