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    Archived pages: 6 . Archive date: 2014-09.

  • Title: Arany Lab
    Descriptive info: .. Home.. Research.. People.. Publications.. In the News.. Contact.. Perelman School of Medicine.. University of Pennsylvania.. Last Update August/2014..

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  • Title: Arany Lab
    Descriptive info: EditRegi.. on1.. The lab focuses on the gene regulatory events underlying cardiovascular metabolism.. The heart and skeletal muscle are highly metabolically active tissues.. Their rates of energy consumption, choice of substrates, and method of catabolism can vary widely.. Aberrant generation or use of energy in these tissues can lead to various diseases, including myopathies and heart failure.. Conversely, optimal handling of energy improves exercise performance, and can have beneficial impact on chronic diseases like diabetes.. Energy in the cell is most efficiently generated by complete oxidation, in the mitochondria, of substrates like sugars and fat.. ATP is abundantly generated in the process, while free oxygen is obligatorily reduced to water.. The generation and regulation of mitochondria is complex and highly regulated.. Importantly, the proper delivery of oxygen and nutrients must also be closely coordinated with mitochondrial function.. Accordingly, highly oxidative tissues are almost invariably also highly vascular.. The gene regulatory networks underlying these processes are only beginning to be understood.. Transcriptional co-activators are proteins that interact with DNA-bound transcription factors to regulate gene expression.. It is likely that most if not all transcription factors require co-activators.. Certain co-activators are highly regulated and integrate extracellular cues to affect gene regulation.. Probably the best example of this is the small family of PGC-1 co-activators (PGC-1α, PGC-1β, and PRC).. The PGC-1’s interact with a number of chromatin-bound transcription factors, including most nuclear receptors.. The PGC-1’s assist in the activation of the basal transcriptional machinery, including the mediator complex; assist in the recruitment of chromatin-modifying enzymes such as histone acetylases like p300; and help coordinate transcription with the splicing machinery.. The result is robust gene induction.. The  ...   increase in vasculature density in PGC-1α transgenic animals.. The induction of VEGF by PGC-1α requires the co-activation of ERRα on conserved binding sites found in the promoter and in a newly identified enhancer within the first intron of the VEGF gene.. Hence, PGC-1α and ERRα, major regulators of mitochondrial function in response to exercise and other stimuli, also control a novel angiogenic pathway that delivers needed oxygen and substrates.. In addition, PGC-1α also appears to play a specific role in the response to ischemia.. PGC-1α is induced by withdrawal of nutrients and oxygen, and full induction of VEGF by these conditions requires PGC-1α.. PGC-1α -/- mice show a striking failure to normally reconstitute blood flow to the limb after an ischemic insult.. Conversely, transgenic expression of PGC-1α in skeletal muscle is protective.. Hence, PGC-1α plays a critical role in the regulation of angiogenesis, both in health and disease.. The lab currently focuses on addressing a number of questions:.. 1.. What is the role of PGC-1 coactivators in regulating angiogenesis in various physiological and pathophysiological contexts?.. 2.. What is the role of PGC-1 coactivators in regulating cardiac and skeletal muscle metabolism?.. 3.. How are genes of oxidative phosphorylation and mitochondrial biology regulated during hypoxia and ischemia?.. 4.. What transcriptional networks regulate metabolic changes and angiogenesis in cardiac and skeletal muscle?.. We take a multidisciplinary approach to these questions, ranging from molecular biology and high-throughput genomics to cell biology and mouse physiology.. Our goal is to understand the gene regulatory events that underlie physiological and pathological metabolic adaptations in both heart and skeletal muscle.. Harvard Medical School.. Beth Israel Deaconess Medical Center.. Last Update July/2008..

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  • Title: Arany Lab
    Descriptive info: EditRe.. gion1.. Zolt Arany, MD PhD, P.. I.. Education:.. • B.. A.. Biochemical Sciences, Harvard College, 1989.. • PhD.. Biological and Biochemical Sciences, Harvard University, 1995.. • MD.. Medicine, Harvard Medical School, 1998.. • Internship in Medicine, Massachusetts General Hospital, 1999.. • Residency in Medicine, Massachusetts General Hospital, 2001.. • Fellowship in Cardiovascular Medicine, Brigham and Women’s Hospital, 2005.. Jian Li, MD.. Lab Manager.. James  ...   Atsushi Hoshino, MD PhD,.. Cholsoon Jang.. Grad Student.. Laura Liu.. George Huang.. Med Student.. Zhipeng Hu.. Visiting Student.. Past Lab Members.. Glenn C Rowe, PhD,.. Naoki Sawada, MD PhD,.. Srilatha Raghuram, PhD,.. Aihua Jiang, MD PhD,.. Adeel Safdar, PhD,.. Jonathan (Yoni) Shoag.. Amrita Goyal.. Robyn Thom.. Undergrad Student.. Luisa Baca.. Student Intern.. Jessica Chinsomboon.. Research Assistant.. Nicole Koulisis.. Ian Patten.. Caitlin Farrell.. Sophia Bampoh.. Tiffany Desouza..

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  • Title: Arany Lab
    Descriptive info: EditR.. egion1.. Selected Recent Articles.. Rowe GC, Raghuram S, Jang C, Nagy J, Patten IS, Goyal A, Chan MC, Liu L, Jiang A, Spokes K, Beeler DL, Dvorak HF, Aird WC, Arany Z.. PGC-1α Induces SPP1 to Activate Macrophages and Orchestrate Functional Angiogenesis in Skeletal Muscle.. Circ Res 2014 Jul 19 (In press).. Arany ZP, Walker CM, Wang L.. Case records of the Massachusetts General Hospital.. Case 22-2014.. A 40-year-old woman with postpartum dyspnea and hypoxemia.. N Engl J Med.. 2014 Jul 17;371(3):261-9.. Thom R, Rowe GC, Jang C, Safdar A, Arany Z.. Hypoxic Induction of Vascular Endothelial Growth Factor (VEGF) and Angiogenesis in Muscle by Truncated Peroxisome Proliferator-Activated Receptor Gamma Coactivator (PGC)-1alpha.. JBC 2014 March 28, 289 (13) 8810-8817.. Sawada N, Jiang A, Takizawa F, Safdar A, Manika A, Tesmenitsky Y, Kang KT, Bischoff J, Kalwa H, Sartoretto JL, Kamei Y, Benjamin LE, Watada H, Ogawa Y, Higashikuni Y, Kessinger CW, Jaffer FA, Michel T, Sata M, Croce K, Tanaka R, Arany Z.. Endothelial PGC-1α Mediates Vascular Dysfunction in Diabetes.. Cell Met 2014 Feb 4;19(2):246-58.. Chan MC, Rowe GC, Raghuram S, Patten IS, Farrell C, Arany Z.. Post-natal induction of PGC-1alpha protects against severe muscle dystrophy independently of utrophin.. Skeletal Muscle.. 2014 Jan 22;4(1):2.. Bello N, Hurtado Rendon IS, Arany Z.. The relationship between Preeclampsia and Peripartum Cardiomyopathy: a Systematic Review and Meta-Analysis.. J Am Coll Cardiol 2013 Aug 23 S0735-1097(13)04005-9.. Rowe GC, Patten IS, Zsengeller ZK, El-Khoury R, Okutsu M, Bampoh S, Koulisis N, Farrell C, Hirshman MF, Yan Z, Goodyear LJ, Rustin P, Arany Z.. Disconnecting mitochondiral content from respiratory chain capacity in PGC-1 deficient skeletal muscle.. Cell Rep 2013 May 30;3(5):1449-56.. Haq R, Shoag J, Andreu-Perez P, Yokoyama S, Edelman H, Rowe GC, Frederick DT, Hurley AD, Nellore A, Kung AL, Wargo JA, Song JS, Fisher DE, Arany Z, Widlund HR.. Oncogenic BRAF Regulates Oxidative Metabolism via PGC1a and MITF.. Cancer Cell 2013 Mar 18;23(3):302-15.. Shoag J, Haq R, Zhang M, Liu L, Rowe GC, Jiang A, Koulisis N, Farrell C, Amos CI, Wei Q, Lee JE, Zhang J, Kupper TS, Qureshi AA, Cui, Han J, Fisher DE, Arany Z.. PGC-1 Coactivators Regualte MITF and the Tanning Response.. Mol Cell Nov 2013 Jan 10;49(1):145-57.. Saint-Geniez M, Jiang A, Abend S, Liu L, Sweigard H, Connor KM, Arany Z.. PGC-1a Regulates Normal and Pathological Angiogenesis in the Retina.. Am J Pathology 2013 Jan;182(1):255-65.. Rowe GC, El-Khoury R, Patten IS, Rustin P, Arany Z.. PGC-1a is Despensable for Exercise-Induced Mitochondrial Biogenesis in Skeletal Muscle.. PLoS One 2012; 7(7):e41817.. Patten IS, Rana S, Shahul S, Rowe GC, Jang C, Liu L, Hacker M, Rhee JS, Mitchell J, Mahmood F, Hess P, Farrell C, Koulisis N, Khankin EV, Burke SD, Tudorache I, Bauersachs J, delMonte F, Hilfiker-Kleiner D, Karumanchi SA, Arany Z.. Cardiac Angiogenic Imbalance Leads to Peri-partum Cardiomyopathy.. Nature 2012 May  ...   KH, Rosenzweig A, and Spiegelman BM.. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α.. Nature.. 2008; 451: 1008-13.. Arany Z, Wagner BK, Ma Y, Chinsomboon J, Laznik D, and Spiegelman BM.. Gene expression-based screening identifies microtubule inhibitors as inducers of PGC-1α and oxidative phosphorylation.. 2008; 105: 4721-6.. Selected Recent Reviews.. Chan MC and Arany Z.. The many roles of PGC-1α in muscle - recent developments.. Metabolism.. 2014 Apr;63(4):441-451.. Hilfiker-Kleiner D and Arany Z.. Focus on Pregnancy-mediated Heart Vascular Disease.. Cardiovasc Res.. 2014 Mar 15;101(4):543-4.. Liu LX and Arany Z.. Maternal Cardiac Metabolism in Pregnancy.. 2014 Mar 15;101(4):545-53.. Rowe GC, Safdar A, Arany Z.. Running forward: new frontiers in endurance exercise biology.. Circulation.. 2014 Feb 18;129(7):798-810.. Rowe GC and Arany Z.. Genetic models of PGC-1 and glucose metabolism and homeostasis.. Rev Endocr Metab Disord.. 2014 Mar;15(1):21-9.. Jang C and Arany Z.. Metabolism: Sweet enticement to move.. Nature Aug 22;500(7463):409-11.. Patten IS and Arany Z.. PGC-1 coactivators in the cardiovascular system.. Trends Endocriol Metab 2012 Feb;23(2):90-7.. Rowe GC, Jiang A and Arany Z.. PGC-1 coactivators in cardiac development and disease.. Circ Res.. 2010 Oct 1;107(7):825-38.. Shoag J and Arany Z.. Regulation of hypoxia-inducible genes by PGC-1 alpha.. Arterioscler Thromb Vasc Biol 2010 Apr;30(4): 662-6.. Wagner BK and Arany Z.. High-throughput real-time PCR for detection of gene-expression levels.. Methods Mol Biol.. 2009; 486: 167-75.. Arany Z.. PGC-1 coactivators and skeletal muscle adaptations in health and disease.. Curr Opin Genet Dev.. 2008; 18: 426-34.. Selected Articles 1995-2004.. Arany Z, Sellers WR, Livingston DM and Eckner R.. E1A-associated p300 and CREB-associated CBP belong to a conserved family of coactivators.. Cell.. 1994; 77:799-800.. Krek W, Ewen ME, Shirodkar S, Arany Z, Kaelin WG, and Livingston DM.. Negative regulation of the growth promoting transcription factor E2F-1 by a stably bound cyclin A-dependent Protein Kinase.. 1994; 78:161-172.. Arany Z, Newsome D, Oldread L, Livingston DM and Eckner R.. A family of transcriptional adaptor proteins targeted by the E1A oncoprotein.. 1995; 374:81-84.. Arany Z, Huang LE, Eckner RE, Bhattacharya S, Jiang C, Goldberg MA, Bunn HF, and Livingston DM.. An essential role for p300/CBP in the cellular response to hypoxia.. 1996; 93:12969-73.. Bhattacharya S, Eckner R, Grossman S, Oldread E, Arany Z, D'Andrea A, and Livingston DM.. Cooperation of STAT2 and p300/CBP in signaling induced by Interferon-.. 1996; 383:344-7.. Huang LE, Arany Z, Livingston, DM and Bunn HF.. Activation of Hypoxia-inducible transcription factor depends primarily upon redox-sensitive stabilization of its subunit.. J.. Biol.. Chem.. 1996; 271:32253-9.. Eckner R, Ludlow JW, Lill NL, Oldread E, Arany Z, Modjtahedi N, DeCaprio JA, Livingston DM, and Morgan JA.. Association of p300 and CBP with Simian Virus 40 Large T Antigen.. Mol.. 1996; 16:3454-64.. Bhattacharya S, Michels CL, Leung MK, Arany Z, Kung AL, Livingston DM.. Functional role of p35srj, a novel p300/CBP binding protein, during transactivation by HIF-1.. Genes Development.. 1999; 13:64-75..

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  • Title: Arany Lab
    Descriptive info: •.. First Calabresi Prize honors cardiovascular researcher.. http://bbs.. yale.. edu/about/article.. aspx?id=7107.. Dvorak Young Investigator Awards Recognize the Promising Work of BIDMC's Young Scientists.. http://www.. bidmc.. org/News/In-Research/2013/October/Dvorak-Awards.. aspx.. Guest blog by Carlos Moraes: PGC-1α and 1ß in skeletal muscle: Are they essential for mitochondrial biogenesis and normal muscle function?.. http://news.. cell.. com/cellreports/cell-reports/guest-blog-by-carlos-moraes-pgc-1α-and-1s-in-skeletal-muscle-are-they-essential-for-mitochondrial-biogenesis-and-normal-muscle-function.. Nature Reviews Cancer 13, 296-297 (May 2013): Melanoma: More horses.. nature.. com/nrc/journal/v13/n5/full/nrc3512.. html.. Pigment Cell Melanoma Res Mar 2013: The masters talk: the PGC-1α–MITF axis as a melanoma energizer..  ...   go.. com/Health/HeartFailureNews/pregnancy-related-heart-failure/story?id=16311260#.. T-R8h47lR1A.. Science STKE Editor’s Choice.. http://stke.. sciencemag.. org/cgi/content/abstract/sigtrans;2/102/ec403.. New England Journal of Medicine.. Metabolism and Therapeutic Angiogenesis.. http://content.. nejm.. org/cgi/content/short/358/23/2511.. org/cgi/content/abstract/sigtrans;1/8/ec72.. Developmental Cell Preview.. Hungry for Blood Vessels: Linking Metabolism and Angiogenesis.. Dev Cell.. 2008 Mar;14(3):313-4.. •.. Harvard Gazette 08: New way to grow blood vessels.. harvard.. edu/gazette/story/2008/02/research-in-brief/.. • Harvard Medical School Focus Magazine 08.. :.. Metabolic regulator has hand in regulating Vessel Growth.. http://archives.. focus.. hms.. edu/2008/030708/cell_biology.. shtml.. Harvard Gazette 07:.. Mystery muscles make mightier mice.. edu/gazette/story/2007/02/mystery-muscles-make-mightier-mice/..

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  • Title: Arany Lab
    Descriptive info: EditRegion1.. Contact info:.. Zolt Arany, MD PhD.. Associate Professor Medicine.. Cardiovascular Institute.. Smilow Center for Translational Research.. 3400 Civic Center Boulevard, Bldg 421.. Philadelphia, PA 19104.. zarany@mail.. med.. upenn.. edu..

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  • Archived pages: 6