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Michel Bernier, Ph.D., Investigator Diabetes Section Laboratory of Clinical Investigation E-mail: bernierm@vax.irp.nia.nih.gov |
| Biography: Dr. Bernier received his Ph.D. from the University of Montreal, Canada, in 1983, and completed two postdoctoral fellowships. The first one was held at INSERM U.162 in Lyon, France, and the second one at the Johns Hopkins University School of Medicine in Baltimore. He was an assistant professor of Biochemistry at McGill University in Canada before joining the NIA in 1990. His current projects include investigation of the molecular mechanisms linking inflammation with insulin resistance and aging. He is a member of the American Diabetes Association and the Endocrine Society. |
| Research Interests: The main focus of Michel Bernier’s laboratory is to elucidate the molecular mechanisms by which chronic low-grade inflammation participates in insulin resistance, oncogenesis and aging through posttranslational modification of select signaling proteins using cells in culture and in vivo models. His lab examined two key intracellular signaling pathways involved in inflammation, metabolism and cancer, namely the IKK/NF-kB and JAK/STAT3 pathways. His team has discovered the reversible formation of a mixed disulfide between glutathione and the transcription factor, STAT3, in response to pyrrolidine dithiocarbamate, thereby providing protection of protein cysteines from oxidative stress while conferring resistance to IL-6 inhibition of insulin signaling in hepatocytes. His lab is currently examining the contribution of the molecular chaperone Hsp90a and the associated up-regulation of stress response pathways in these processes. In human hepatocarcinoma cells, mRNA expression profiling revealed reciprocal changes in gene expression levels attributed to mTOR regulation when comparing IL-6 and pyrrolidine dithiocarbamate. Because of the central role for mTOR in lifespan extension through adaptive energy metabolism, strategies aimed at targeting mTOR may be therapeutically useful in fighting human metabolic diseases. Experiments are being carried out to determine the modalities that control the mTOR regulatory pattern, with an emphasis on microRNA, nuclear receptors, and transcription factors. |
Dr. Bernier’s laboratory is also actively involved in a number of collaborative studies whose aims are to determine the contribution of chemokine and adipogenic signaling in regulating cellular microenvironment associated with cancer and aging. |
| Selected Publications: |
| Song S, Kole S, Precht P, Pazin MJ, Bernier M. Activation of heat shock factor 1 plays a role in pyrrolidine dithiocarbamate-mediated expression of the co-chaperone BAG3. Int J Biochem Cell Biol. 2010 Aug 6. [Epub ahead of print] |
| Mello Coelho V, Bunbury A, Rangel LB, Giri B, Weeraratna A, Morin PJ, Bernier M, Taub DD. Fat-storing multilocular cells expressing CCR5 increase in the thymus with advancing age: potential role for CCR5 ligands on the differentiation and migration of preadipocytes. Int J Med Sci. 2010; 7(1):1-14. |
| He HJ, Zong Y, Bernier M, Wang L. Sensing the insulin signaling pathway with an antibody array. Proteomics – Clinical Applications 2009; 3(12):1440-1450. |
| Xie Y, Kole S, Precht P, Pazin MJ, Bernier M. S-glutathionylation impairs signal transducer and activator of transcription 3 activation and signaling. Endocrinology. 2009; 150(3):1122-31 |
Marszałł MP, Moaddel R, Kole S, Gandhari M, Bernier M, Wainer IW. Ligand and protein fishing with heat shock protein 90 coated magnetic beads. Anal Chem. 2008; 80(19):7571-5. |
| Zhu M, Lee GD, Ding L, Hu J, Qiu G, de Cabo R, Bernier M, Ingram DK, Zou S. Adipogenic signaling in rat white adipose tissue: modulation by aging and calorie restriction. Exp Gerontol. 2007; 42(8):733-44. |
| He HJ, Zhu TN, Xie Y, Fan J, Kole S, Saxena S, Bernier M. Pyrrolidine dithiocarbamate inhibits interleukin-6 signaling through impaired STAT3 activation and association with transcriptional coactivators in hepatocytes. J Biol Chem. 2006; 281(42):31369-79. |
| Bernier M, Kwon YK, Pandey SK, Zhu TN, Zhao RJ, Maciuk A, He HJ, de Cabo R, Kole S. Binding of manumycin A inhibits IkB kinase b activity. J Biol Chem. 2006; 281(5):2551-61. |
| Reviews: |
| Zheng B, Han M, Bernier M, Wen JK. Nuclear actin and actin-binding proteins in the regulation of transcription and gene expression. FEBS J. 2009; 276(10):2669-85. |
| Bernier M, He HJ, Kwon YK, Jang HJ. The roles of phospholipase C-g 1 and actin-binding protein filamin A in signal transduction of the insulin receptor. Vitam Horm. 2004; 69:221-47. |
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