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Navdeep S. Chandel, PhDAssociate Professor
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Please visit the Chandel lab home page: http://www.chandellab.com/
The major function of mitochondria in cellular homeostasis has historically been the generation of energy through oxidative phosphorylation. However, we and others have demonstrated that mitochondria can serve as a signaling organelle. The projects in my lab are driven by the hypothesis that when cells encounter stress the mitochondria serve as key regulators of biological outcomes that include the induction of adaptive genes, cellular proliferation, senescence and death.
Hypoxic and oncogenic stress will be used to test our hypothesis. The microenvironment of stem cells and tumor cells is hypoxic. Failure to adapt to hypoxia results in tumor regression and loss of stem cell multipotency. Oncogenes are essential regulators of tumorigenesis including the conversion of stem cells to tumor cells. We hypothesize that the degree of hypoxic or oncogenic stress can release low levels of mitochondrial ROS to activate genes for cellular adaptation. Conversely, higher levels of mitochondrial ROS induce senescence. The degree of hypoxic or oncogenic stress is likely to regulate whether mitochondria provide substrates for lipid synthesis to allow cellular proliferation or commit to apoptosis through the release of cytochrome c during hypoxic or oncogenic stress. We are currently examining how mitochondria serve as a signaling organelle for stem cells and cancer.
Bell EL, Klimova TA, Eisenbart J, Moraes CT, Murphy MP, Budinger GR, Chandel NS. The Qo site of the mitochondrial complex III is required for the transduction of hypoxic signaling via reactive oxygen species production. J Cell Biol. 2007 Jun 18;177(6):1029-36.
Bell EL, Klimova TA, Eisenbart J, Schumacker PT, Chandel NS. Mitochondrial ROS trigger HIF-dependent extension of replicative lifespan during hypoxia. Mol Cell Biol. 2007 Aug;27(16):5737-45.
Brunelle JK, Shroff EH, Perlman H, Strasser A, Moraes CT, Flavell RA, Danial NN, Keith B, Thompson CB, Chandel NS. Loss of Mcl-1 protein and inhibition of electron transport chain together induce anoxic cell death. Mol Cell Biol. 2007 Feb;27(4):1222-35.
Budinger GR, Mutlu GM, Eisenbart J, Fuller AC, Bellmeyer AA, Baker CM, Wilson M, Ridge K, Barrett TA, Lee VY, Chandel NS. Proapoptotic Bid is required for pulmonary fibrosis. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4604-9.
Emerling BM, Chandel NS. Oxygen sensing: getting pumped by sterols. Science STKE. 2005 Jun 21;2005(289):pe30.
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View Publications by Navdeep Chandel listed in the National Library of Medicine (PubMed). |
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