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| Systems Biology | Inborn Errors of Energy Metabolism | Common Human Diseases |
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| Mitochondrial Dysfunction in Common Human Diseases |
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We previously used transcriptional profiling to discover that the common form of type 2 diabetes mellitus is characterized by a gradual decline in the expression and activity of mitochondrial oxidative phosphorylation (OXPHOS). This “mitochondrial signature” is subtle at the level of individual genes and could not have been detected using traditional experimental or analytical strategies focused on single genes. The changes are concordant across scores of mitochondrial genes, and hence, statistically robust and likely biologically meaningful. Our work has been corroborated by other groups and has contributed to the “mitochondrial hypothesis” for type 2 diabetes. We are collaborating with leading human geneticists to determine if genetic variation in OXPHOS components or its regulatory machinery contribute to the inherited risk of developing type 2 diabetes mellitus. |
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| Selected Publications |
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Metabolic profiling of the human response to a glucose challenge reveals distinct axes of insulin sensitivity
Shaham O, Wei R, Wang TJ, Ricciardi C, Lewis GD, Vasan RS, Carr SA, Thadhani R, Gerszten RE, Mootha VK.
Molecular Systems Biology doi:10.1038/msb.2008.50. 2008 |
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PGC-1α responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes
Mootha VK, Lindgren CM, Eriksson KF, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman BM, Lander ES, Hirschhorn JN, Altshuler D, Groop LC.
Nature Genetics 34(3):267-73. 2003 |
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Gene set enrichment analysis: A knowledge-based approach for Interpreting genomewide expression profiles
Subramanian AS, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP.
Proceedings of the National Academy of Sciences U.S.A., 102:15545-50. 2005
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