Our laboratory is molecularly dissecting easily accessible cells important for atherosclerosis to gain new insights into the disease process. We are utilizing unbiased global genetic screens such as Serial Analysis of Gene Expression (SAGE) to study circulating human monocytes as they differentiate into plaque macrophages. Using this approach, we have identified the protooncogene FOS as a reactive disease marker expressed in monocytes and other transcriptional modulators in macrophages. In addition, we have observed networks of genes belonging to various functional pathways that are critical for inflammatory function. Studies are underway to determine the utility of the disease markers and the role of candidate genes in atherosclerosis. Another area of interest to our laboratory is the role of tumor suppressor gene p53 in cardiovascular function. We have previously shown that p53 can potently generate reactive oxidants in the mitochondria and that it is involved in chemotherapy induced heart failure. We are now investigating novel mechanisms of mitochondrial regulation by the nucleus that may be important for energy and oxidant generation. Ongoing studies indicate that these novel pathways may not only have direct consequences on cardiovascular function but that they may also be important in inflammatory function. Various molecular techniques such as mouse conditional and human somatic cell gene knockout models are being used to address these questions.
| 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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