Research Topics
Genomes and Genes | T FinkelSummaryAffiliation: National Institutes of Health Country: USA Publications
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Publications
Redox-dependent transcriptional regulationHongjun Liu
National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Circ Res 97:967-74. 2005..This review summarizes the recent progress on how cellular redox status can regulate transcription-factor activity and the implications of this regulation for cardiovascular disease...
Stem cell aging: what bleach can teachJie Liu
Nat Med 12:383-4. 2006
Intracellular redox regulation by the family of small GTPasesToren Finkel
Cardiology Branch, National Heart Lungs and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892 1454, USA
Antioxid Redox Signal 8:1857-63. 2006....
Cell biology: a clean energy programmeToren Finkel
Nature 444:151-2. 2006
Free radicals and senescenceTeng Lu
Translational Medicine Branch, NHLBI, NIH, Building 10 CRC 5 3330, Bethesda, MD 20892, USA
Exp Cell Res 314:1918-22. 2008..Although these data tend to support a role for ROS in mediating senescence, significant questions remain as to whether ROS act in a random or specific fashion and what precise oxidant species acts as the potential senescence trigger...
Relief with rapamycin: mTOR inhibition protects against radiation-induced mucositisToren Finkel
Center for Molecular Medicine, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cell Stem Cell 11:287-8. 2012..In normal tissues, rapamycin prevents epithelial stem cell senescence by reducing oxidative stress through increased MnSOD...
Signal transduction by mitochondrial oxidantsToren Finkel
Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 287:4434-40. 2012....
Reactive oxygen species and signal transductionT Finkel
Laboratory of Molecular Biology, NHLBI, NIH, Bethesda, MD 20814 1622, USA
IUBMB Life 52:3-6. 2001..This review will focus on the progress in the rapid emerging area of oxidant or redox-dependent signal transduction and speculate how these insights might alter our view and treatment of diseases thought to be caused by oxidative stress...
Radical medicine: treating ageing to cure diseaseToren Finkel
Cardiovascular Branch ofthe National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, Maryland 20892, USA
Nat Rev Mol Cell Biol 6:971-6. 2005....
Oxidant signals and oxidative stressToren Finkel
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892 1622, USA
Curr Opin Cell Biol 15:247-54. 2003..These new studies have significantly altered our understanding of how reactive oxygen species participate in diverse processes from tumourigenesis to ageing...
The common biology of cancer and ageingToren Finkel
Cardiology Branch, NIH, NHLBI, Building 10 CRC 5 3330, 10 Center Drive, Bethesda, Maryland 20892, USA
Nature 448:767-74. 2007..Here we review the series of key observations that has led to a complex but growing convergence between our understanding of the biology of ageing and the mechanisms that underlie cancer...
Oxidants, oxidative stress and the biology of ageingT Finkel
Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute National Institutes of Health, Bethesda, Maryland 20892 1622, USA
Nature 408:239-47. 2000..Here we review evidence that the appropriate and inappropriate production of oxidants, together with the ability of organisms to respond to oxidative stress, is intricately connected to ageing and life span...
Redox-dependent signal transductionT Finkel
Laboratory of Molecular Biology, National Heart Lung and Blood Institute, National Institutes of Health, Bldg 10 6N 240, 10 Center Drive, 20892 1622, Bethesda, MD, USA
FEBS Lett 476:52-4. 2000..This review will focus on the effects of ROS on signal transduction pathways, the molecules that regulate intracellular ROS production and the potential protein targets of oxidants...
Signal transduction by reactive oxygen speciesToren Finkel
Center for Molecular Medicine, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Cell Biol 194:7-15. 2011....
Redox regulation of forkhead proteins through a p66shc-dependent signaling pathwayShino Nemoto
Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10 6N 240, 10 Center Drive, Bethesda, MD 20892 1622, USA
Science 295:2450-2. 2002..These results demonstrate an important functional relation between three distinct elements linked to aging: forkhead proteins, p66shc, and intracellular oxidants...
Bmi1 regulates mitochondrial function and the DNA damage response pathwayJie Liu
Translational Medicine Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 459:387-92. 2009....
Endothelial progenitor cells and endothelial dysfunctionJ M Hill
The Laboratory of Molecular Biology; Cardiology Branch of the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA
Vox Sang 87:31-7. 2004
Reactive oxygen species as mediators of cellular senescenceRenata Colavitti
Cardiovascular Branch, NHLBI, NIH, Bethesda, Maryland 20892-1454, USA
IUBMB Life 57:277-81. 2005..In particular, we review the concept that intracellular reactive oxygen species function as signalling molecules and that oxidants play a central role as mediators of cellular senescence...
The ClinSeq Project: piloting large-scale genome sequencing for research in genomic medicineLeslie G Biesecker
National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Genome Res 19:1665-74. 2009..The early experiences with ClinSeq illustrate how large-scale medical sequencing can be a practical, productive, and critical component of research in genomic medicine...
A selective requirement for 53BP1 in the biological response to genomic instability induced by Brca1 deficiencyLiu Cao
Translational Medicine Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Mol Cell 35:534-41. 2009..These observations may have important implications for Brca1-mediated tumor formation as well as for the molecular pathway leading from genomic instability to organismal aging...
53BP1 inhibits homologous recombination in Brca1-deficient cells by blocking resection of DNA breaksSamuel F Bunting
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cell 141:243-54. 2010..Our results illustrate that HR and NHEJ compete to process DNA breaks that arise during DNA replication and that shifting the balance between these pathways can be exploited to selectively protect or kill cells harboring Brca1 mutations...
Strategic plan for lung vascular research: An NHLBI-ORDR Workshop ReportSerpil Erzurum
Department of Pathobiology, Cleveland Clinic, Cleveland, Ohio, USA
Am J Respir Crit Care Med 182:1554-62. 2010..Recommendations from this workshop will be used within the Lung Vascular Biology and Disease Extramural Research Program for planning and strategic implementation purposes...
Endothelial progenitor cellsAarif Y Khakoo
National Institutes of Health, National Heart, Lung, and Blood Institute, Cardiovascular Branch, Laboratory of Molecular Biology, Bethesda, Maryland 21284, USA
Annu Rev Med 56:79-101. 2005..We review experimental results obtained from both animal studies and recent clinical trials that suggest this cell type may have tremendous therapeutic potential for a wide range of human diseases...
A role for mitochondria as potential regulators of cellular life spanDong Xu
Cardiovascular Branch, NHLBI, NIH, Building 10/6N-240, 10 Center Drive, Bethesda, MD 20892-1622, USA
Biochem Biophys Res Commun 294:245-8. 2002..These results suggest that mitochondria appear to play a central role in regulating cellular life span...
Signal transduction by reactive oxygen species in non-phagocytic cellsT Finkel
National Institutes of Health, Bethesda, Maryland 20892 1650, USA
J Leukoc Biol 65:337-40. 1999..Nonetheless, numerous recent studies have implicated a dynamic change in the intracellular redox state as an important determinant in a host of cellular decisions ranging from growth, to apoptosis, to cellular senescence...
Apoptosis in vascular disease: opportunities for genetic therapeutic interventionT M Johnson
Cardiology Branch, National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA gov
Semin Interv Cardiol 1:195-202. 1996..These observations suggest that the transfer of apoptosis-inducing genes into vascular lesions may be a feasible, non-inflammatory strategy to eliminate the cellular components of restenotic and atherosclerotic plaques...
TOR and aging: less is moreStefan M Schieke
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Cell Metab 5:233-5. 2007..A new study in this issue of Cell Metabolism (Bonawitz et al., 2007) suggests that the TOR pathway controls mitochondrial respiration in yeast and that the harder mitochondria work, the longer yeast live...
Interplay among BRCA1, SIRT1, and Survivin during BRCA1-associated tumorigenesisRui Hong Wang
Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
Mol Cell 32:11-20. 2008..These findings suggest that resveratrol treatment serves as an excellent strategy for targeted therapy for BRCA1-associated breast cancer...
The mammalian longevity-associated gene product p66shc regulates mitochondrial metabolismShino Nemoto
Cardiology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bldg 10 6N 240, 10 Center Drive, Bethesda, MD 20892 1622, USA
J Biol Chem 281:10555-60. 2006..These results demonstrate that p66(shc) regulates mitochondrial oxidative capacity and suggest that p66(shc) may extend life span by repartitioning metabolic energy conversion away from oxidative and toward glycolytic pathways...
Circulating endothelial progenitor cells, vascular function, and cardiovascular riskJonathan M Hill
Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892-1622, USA
N Engl J Med 348:593-600. 2003..These findings suggest that endothelial injury in the absence of sufficient circulating progenitor cells may affect the progression of cardiovascular disease...
Redox regulation of Cdc25CPavel A Savitsky
Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1622, USA
J Biol Chem 277:20535-40. 2002..These results suggest that oxidative stress may induce cell cycle arrest in part through the degradation of Cdc25C...
Augmented Wnt signaling in a mammalian model of accelerated agingHongjun Liu
Cardiology Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892, USA
Science 317:803-6. 2007..Both in vitro and in vivo, continuous Wnt exposure triggered accelerated cellular senescence. Thus, klotho appears to be a secreted Wnt antagonist and Wnt proteins have an unexpected role in mammalian aging...
Mitochondria, oxidants, and agingRobert S Balaban
Laboratory of Cardiac Energetics, National Institutes of Health, Bethesda, Maryland 20892, USA
Cell 120:483-95. 2005..Here we review the evidence that both supports and conflicts with the free radical theory and examine the growing link between mitochondrial metabolism, oxidant formation, and the biology of aging...
Regulation of endothelial cell adherens junctions by a Ras-dependent signal transduction pathwayD D Hegland
Cardiology Branch, National Heart, Lung and Blood Institute, NIH, Bethesda, Maryland, 20892, USA
Biochem Biophys Res Commun 260:371-6. 1999....
Ras regulates NFAT3 activity in cardiac myocytesM Ichida
Laboratory of Molecular Biology, NHLBI, National Institutes of Health, Bethesda, Maryland 20892, USA
J Biol Chem 276:3524-30. 2001..Taken together, these results imply that, in cardiac myocytes, a Ras-regulated pathway involving stimulation of mitogen-activated protein kinase regulates NFAT3 activity...
Regulation of cellular oncosis by uncoupling protein 2Edward M Mills
Cardiovascular Branch, NHLBI/National Institutes of Health, 10 Center Drive, Bldg. 10/6N-240, Bethesda, MD 20892, USA
J Biol Chem 277:27385-92. 2002..These results suggest that distinct genetic programs may regulate the cellular response to either apoptotic or oncotic stimuli...
Detection and affinity purification of oxidant-sensitive proteins using biotinylated glutathione ethyl esterDaniel M Sullivan
Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
Methods Enzymol 353:101-13. 2002
Oxidants painting the cysteine chapel: redox regulation of PTPsDong Xu
Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, MD 20892, USA
Dev Cell 2:251-2. 2002..A new study now demonstrates that ligand-stimulated intracellular hydrogen peroxide can specifically and reversibly regulate the activity of protein tyrosine phosphatases...
A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasisBong Hyun Ahn
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
Proc Natl Acad Sci U S A 105:14447-52. 2008..These results implicate protein acetylation as an important regulator of Complex I activity and demonstrate that Sirt3 functions in vivo to regulate and maintain basal ATP levels...
A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagyIn Hye Lee
Translational Medicine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892
Proc Natl Acad Sci U S A 105:3374-9. 2008..These results suggest that the Sirt1 deacetylase is an important in vivo regulator of autophagy and provide a link between sirtuin function and the overall cellular response to limited nutrients...
Xanthine oxidoreductase is an endogenous regulator of cyclooxygenase-2Toshio Ohtsubo
Cardiovascular Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD 20892 1622, USA
Circ Res 95:1118-24. 2004..In addition, these results suggest a novel molecular link between cellular injury and the inflammatory response...
Identification of a specific molecular repressor of the peroxisome proliferator-activated receptor gamma Coactivator-1 alpha (PGC-1alpha)Masaru Ichida
Laboratory of Molecular Biology, Cardiovascular Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Biol Chem 277:50991-5. 2002..In addition, our results suggest that other co-activators might also have specific repressors, thereby identifying another layer of combinatorial complexity in transcriptional regulation...
Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagyJ Julie Wu
Translational Medicine Branch, National Heart Lung and Blood Institute, NIH, Bethesda, MD 20892, USA
Aging (Albany NY) 1:425-37. 2009..Taken together, these results demonstrate the potential role of mitochondrial dysfunction and oxidative stress in autophagy related pathology...
Nutrient availability regulates SIRT1 through a forkhead-dependent pathwayShino Nemoto
Cardiovascular Branch, National Heart, Lung, and Blood Institute NHLBI, Bethesda, MD 20892, USA
Science 306:2105-8. 2004..SIRT1 expression was not induced in starved p53-deficient mice. Thus, in mammalian cells, p53, Foxo3a, and SIRT1, three proteins separately implicated in aging, constitute a nutrient-sensing pathway...
Vascular effects following homozygous disruption of p47(phox) : An essential component of NADPH oxidaseE Hsich
Laboratory of Molecular Biology, National Heart, Lung, and Blood Institute, and the Laboratory of Host Defenses, National Institute of Health, Bethesda, MD 20892, USA
Circulation 101:1234-6. 2000..We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure...
Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery diseaseTiffany M Powell
Cardiovascular Branch, National Heart, Lung, and Blood Institute and the Department of Transfusion Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892-1650, USA
Arterioscler Thromb Vasc Biol 25:296-301. 2005..Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair in coronary artery disease patients must be tested in clinical trials...
SIRT1 functionally interacts with the metabolic regulator and transcriptional coactivator PGC-1{alpha}Shino Nemoto
Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1454, USA
J Biol Chem 280:16456-60. 2005..These results provide a direct link between the sirtuins, a family of proteins linked to lifespan determination and PGC-1alpha, a coactivator that regulates cellular metabolism...
Phosphorylation of p66Shc and forkhead proteins mediates Abeta toxicityWanli W Smith
Molecular Neurobiology Unit, Laboratory of Cellular and Molecular Biology, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
J Cell Biol 169:331-9. 2005..These findings underscore the potential usefulness of JNK, p66Shc, and forkhead proteins as therapeutic targets for AD...
Pharmacology: uncoupling the agony from ecstasyEdward M Mills
Cardiovascular Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892 1622, USA
Nature 426:403-4. 2003..Our findings indicate that UCP-3 is important in MDMA-induced hyperthermia and point to a new therapeutic direction for solving an increasing public-health problem...
Neutrophils with a license to kill: permeabilized, not stirredToren Finkel
Cardiovascular Branch, NHLBI, NIH, 10 Center Drive, Bethesda, MD 20892, USA
Dev Cell 4:146-8. 2003..Relatively little is known about the intracellular assembly or activation of the oxidase, but Brown et al. in the January issue of Molecular Cell provide a useful strategy involving permeabilized neutrophils to tackle this question...
Human mesenchymal stem cells exert potent antitumorigenic effects in a model of Kaposi's sarcomaAarif Y Khakoo
Laboratory of Molecular Biology, Cardiovascular Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Exp Med 203:1235-47. 2006....
Mitochondrial signaling, TOR, and life spanStefan M Schieke
Cardiology Branch, National Heart, Lung, and Blood Institute, NHLBI, National Institutes of Health, Bethesda, MD 20892-1622, USA
Biol Chem 387:1357-61. 2006..This brief review summarizes the recent progress on how mitochondrial signaling might contribute to the aging process with a particular emphasis on TOR signaling from invertebrates to humans...
Recent progress in the biology and physiology of sirtuinsToren Finkel
Translational Medicine Branch, National Heart Lung and Blood Institute, US National Institutes of Health, Bethesda, Maryland 20892, USA
Nature 460:587-91. 2009..Here we review the recent progress in sirtuin biology, the role these proteins have in various age-related diseases and the tantalizing notion that the activity of this family of enzymes somehow regulates how long we live...
Ageing and the mystery at ArlesShino Nemoto
Nature 429:149-52. 2004
Effect of a histone deacetylase inhibitor on human cardiac massYukitaka Shizukuda
Cardiovasc Drugs Ther 19:89-90. 2005
Cancer gets the Chk'ered flagLiu Cao
Nat Med 12:1354-6. 2006
