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    Heidi A Tissenbaum PhD

    TitleProfessor
    InstitutionUniversity of Massachusetts Medical School
    DepartmentProgram in Molecular Medicine
    AddressUniversity of Massachusetts Medical School
    364 Plantation Street, LRB-621
    Worcester MA 01605
    Phone508-856-5840
      Other Positions
      InstitutionUMMS - Graduate School of Biomedical Sciences
      DepartmentInterdisciplinary Graduate Program

      InstitutionUMMS - Programs, Centers and Institutes
      DepartmentProgram in Gene Function and Expression

        Overview 
        Narrative

        Academic Background

        Heidi Tissenbaum received her B.S. in Biology from Concordia University in Montreal, Quebec, Canada and an M.S. degree in Physiology from the University of Ottawa, in Ontario, Canada. In 1997, she graduated with a Ph.D. in Genetics from Harvard Medical School. From 1997 to 2001, she was a post-doc at MIT where she was supported by the Helen Hay Whitney Foundation. In 2001, Dr. Tissenbaum joined the Program in Gene Function and Expression at the University of Massachusetts Medical School, and also received a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund. Dr. Tissenbaum has received funding from the American Federation of Aging Research, the Worcester Foundation for Biomedical Research, the Concern Foundation, and the National Institute of Aging. Dr. Tissenbaum is also a William Randolph Hearst Young Investigator.

        Dissecting Molecular Mechanisms of the Aging Process

        Photo: Heidi 
Tissenbaum What determines how we age? What defines how long we will live? Is this a clock that is set from birth? How can we tinker with this clock? These are the questions we seek to address in the lab. The ultimate goal of our work is to increase the healthy. reproductive years of individuals; redefining and prolonging healthy middle age.

        We use the nematode C. elegans as our system to study the aging process. Worms have a short, reproducible life span and provide an excellent system for these studies. Similar to mammals, worms have many signaling ptahways that modulate lifespan, metabolism, stress and development. Using this simple system, we can begin to dissect the complex networks that regulate these processes.

        Specific Interests

        1. In C. elegans, the insulin/IGF-1 signaling pathway plays a central role in regulating lifespan, fat storage, stress and development. What are all the genes involved? How is each specific phenotype modulated? Are they modulated together?
        2. How do multiple conserved signaling pathways couple to the insulin/IGF-1 pathway to regulate lifespan? Fat storage? Stress? Development?
        3. How does the forkhead transcription factor DAF-16 function as a central mediator in C. elegans?


        Photo: Heidi 
Tissenbaum

        Rotation Projects

        Potential Rotation Projects

          Project #1: Genetic screen to identify genes that act in the sir-2.1 pathway that regulates aging.

          Project #2: Identify new genes that affect aging by gene dosage.

          Project #3: Create mutations in the C. elegans homologs of genes known to regulate insulin signaling in humans and determine their affects on life span.

        Overall questions of the lab:

        1. Are the general mechanisms of life span conserved? How?


        2. How can we control the genes that affect life span?


        3. Is aging the sums of many processes or are there specific signaling pathways for aging?


        4. How does life span regulation relate to insulin signaling?

        Program Affiliations:

          Gene Function and Expression, Interdisciplinary Graduate Program


        Bibliographic 
        selected publications
        List All   |   Timeline
        1. Bansal A, Kwon ES, Conte D, Liu H, Gilchrist MJ, MacNeil LT, Tissenbaum HA. Transcriptional regulation of Caenorhabditis elegans FOXO/DAF-16 modulates lifespan. Longev Healthspan. 2014; 3:5.
          View in: PubMed
        2. Ritter AD, Shen Y, Fuxman Bass J, Jeyaraj S, Deplancke B, Mukhopadhyay A, Xu J, Driscoll M, Tissenbaum HA, Walhout AJ. Complex expression dynamics and robustness in C. elegans insulin networks. Genome Res. 2013 Jun; 23(6):954-65.
          View in: PubMed
        3. Viswanathan M, Tissenbaum HA. C. elegans sirtuins. Methods Mol Biol. 2013; 1077:39-56.
          View in: PubMed
        4. Parker JA, Vazquez-Manrique RP, Tourette C, Farina F, Offner N, Mukhopadhyay A, Orfila AM, Darbois A, Menet S, Tissenbaum HA, Neri C. Integration of ß-catenin, sirtuin, and FOXO signaling protects from mutant huntingtin toxicity. J Neurosci. 2012 Sep 5; 32(36):12630-40.
          View in: PubMed
        5. Perrin AJ, Gunda M, Yu B, Yen K, Ito S, Forster S, Tissenbaum HA, Derry WB. Noncanonical control of C. elegans germline apoptosis by the insulin/IGF-1 and Ras/MAPK signaling pathways. Cell Death Differ. 2013 Jan; 20(1):97-107.
          View in: PubMed
        6. Tissenbaum HA. Genetics, life span, health span, and the aging process in Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci. 2012 May; 67(5):503-10.
          View in: PubMed
        7. Narasimhan SD, Yen K, Bansal A, Kwon ES, Padmanabhan S, Tissenbaum HA. PDP-1 links the TGF-ß and IIS pathways to regulate longevity, development, and metabolism. PLoS Genet. 2011 Apr; 7(4):e1001377.
          View in: PubMed
        8. Yen K, Narasimhan SD, Tissenbaum HA. DAF-16/Forkhead box O transcription factor: many paths to a single Fork(head) in the road. Antioxid Redox Signal. 2011 Feb 15; 14(4):623-34.
          View in: PubMed
        9. Yen K, Le TT, Bansal A, Narasimhan SD, Cheng JX, Tissenbaum HA. A comparative study of fat storage quantitation in nematode Caenorhabditis elegans using label and label-free methods. PLoS One. 2010; 5(9).
          View in: PubMed
        10. Baur JA, Chen D, Chini EN, Chua K, Cohen HY, de Cabo R, Deng C, Dimmeler S, Gius D, Guarente LP, Helfand SL, Imai S, Itoh H, Kadowaki T, Koya D, Leeuwenburgh C, McBurney M, Nabeshima Y, Neri C, Oberdoerffer P, Pestell RG, Rogina B, Sadoshima J, Sartorelli V, Serrano M, Sinclair DA, Steegborn C, Tatar M, Tissenbaum HA, Tong Q, Tsubota K, Vaquero A, Verdin E. Dietary restriction: standing up for sirtuins. Science. 2010 Aug 27; 329(5995):1012-3; author reply 1013-4.
          View in: PubMed
        11. Kwon ES, Narasimhan SD, Yen K, Tissenbaum HA. A new DAF-16 isoform regulates longevity. Nature. 2010 Jul 22; 466(7305):498-502.
          View in: PubMed
        12. Narasimhan SD, Mukhopadhyay A, Tissenbaum HA. InAKTivation of insulin/IGF-1 signaling by dephosphorylation. Cell Cycle. 2009 Dec; 8(23):3878-84.
          View in: PubMed
        13. Narasimhan SD, Yen K, Tissenbaum HA. Converging pathways in lifespan regulation. Curr Biol. 2009 Aug 11; 19(15):R657-66.
          View in: PubMed
        14. Padmanabhan S, Mukhopadhyay A, Narasimhan SD, Tesz G, Czech MP, Tissenbaum HA. A PP2A regulatory subunit regulates C. elegans insulin/IGF-1 signaling by modulating AKT-1 phosphorylation. Cell. 2009 Mar 6; 136(5):939-51.
          View in: PubMed
        15. Barber LJ, Youds JL, Ward JD, McIlwraith MJ, O'Neil NJ, Petalcorin MI, Martin JS, Collis SJ, Cantor SB, Auclair M, Tissenbaum H, West SC, Rose AM, Boulton SJ. RTEL1 maintains genomic stability by suppressing homologous recombination. Cell. 2008 Oct 17; 135(2):261-71.
          View in: PubMed
        16. Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. Chromatin immunoprecipitation (ChIP) coupled to detection by quantitative real-time PCR to study transcription factor binding to DNA in Caenorhabditis elegans. Nat Protoc. 2008; 3(4):698-709.
          View in: PubMed
        17. Mukhopadhyay A, Pan X, Lambright DG, Tissenbaum HA. An endocytic pathway as a target of tubby for regulation of fat storage. EMBO Rep. 2007 Oct; 8(10):931-8.
          View in: PubMed
        18. Mukhopadhyay A, Tissenbaum HA. Reproduction and longevity: secrets revealed by C. elegans. Trends Cell Biol. 2007 Feb; 17(2):65-71.
          View in: PubMed
        19. Tissenbaum HA. Serotonin's SOS signal. Cell Metab. 2006 Dec; 4(6):415-7.
          View in: PubMed
        20. Wang Y, Oh SW, Deplancke B, Luo J, Walhout AJ, Tissenbaum HA. C. elegans 14-3-3 proteins regulate life span and interact with SIR-2.1 and DAF-16/FOXO. Mech Ageing Dev. 2006 Sep; 127(9):741-7.
          View in: PubMed
        21. Mukhopadhyay A, Oh SW, Tissenbaum HA. Worming pathways to and from DAF-16/FOXO. Exp Gerontol. 2006 Oct; 41(10):928-34.
          View in: PubMed
        22. Deplancke B, Mukhopadhyay A, Ao W, Elewa AM, Grove CA, Martinez NJ, Sequerra R, Doucette-Stamm L, Reece-Hoyes JS, Hope IA, Tissenbaum HA, Mango SE, Walhout AJ. A gene-centered C. elegans protein-DNA interaction network. Cell. 2006 Jun 16; 125(6):1193-205.
          View in: PubMed
        23. Oh SW, Mukhopadhyay A, Dixit BL, Raha T, Green MR, Tissenbaum HA. Identification of direct DAF-16 targets controlling longevity, metabolism and diapause by chromatin immunoprecipitation. Nat Genet. 2006 Feb; 38(2):251-7.
          View in: PubMed
        24. Wang Y, Tissenbaum HA. Overlapping and distinct functions for a Caenorhabditis elegans SIR2 and DAF-16/FOXO. Mech Ageing Dev. 2006 Jan; 127(1):48-56.
          View in: PubMed
        25. Grabowski MM, Svrzikapa N, Tissenbaum HA. Bloom syndrome ortholog HIM-6 maintains genomic stability in C. elegans. Mech Ageing Dev. 2005 Dec; 126(12):1314-21.
          View in: PubMed
        26. Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab. 2005 Jul; 2(1):35-42.
          View in: PubMed
        27. Oh SW, Mukhopadhyay A, Svrzikapa N, Jiang F, Davis RJ, Tissenbaum HA. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc Natl Acad Sci U S A. 2005 Mar 22; 102(12):4494-9.
          View in: PubMed
        28. Tissenbaum HA, Guarente L. Model organisms as a guide to mammalian aging. Dev Cell. 2002 Jan; 2(1):9-19.
          View in: PubMed
        29. McVey M, Kaeberlein M, Tissenbaum HA, Guarente L. The short life span of Saccharomyces cerevisiae sgs1 and srs2 mutants is a composite of normal aging processes and mitotic arrest due to defective recombination. Genetics. 2001 Apr; 157(4):1531-42.
          View in: PubMed
        30. Tissenbaum HA, Guarente L. Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature. 2001 Mar 8; 410(6825):227-30.
          View in: PubMed
        31. Tissenbaum HA, Hawdon J, Perregaux M, Hotez P, Guarente L, Ruvkun G. A common muscarinic pathway for diapause recovery in the distantly related nematode species Caenorhabditis elegans and Ancylostoma caninum. Proc Natl Acad Sci U S A. 2000 Jan 4; 97(1):460-5.
          View in: PubMed
        32. Tissenbaum HA, Ruvkun G. An insulin-like signaling pathway affects both longevity and reproduction in Caenorhabditis elegans. Genetics. 1998 Feb; 148(2):703-17.
          View in: PubMed
        33. Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G. The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997 Oct 30; 389(6654):994-9.
          View in: PubMed
        34. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997 Aug 15; 277(5328):942-6.
          View in: PubMed
        35. Morris JZ, Tissenbaum HA, Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996 Aug 8; 382(6591):536-9.
          View in: PubMed
        36. Tissenbaum HA, Parry DJ. The effect of partial denervation of tibialis anterior (TA) muscle on the number and sizes of motorneurons in TA motornucleus of normal and dystrophic (C57BL dy2j/dy2j) mice. Can J Physiol Pharmacol. 1991 Nov; 69(11):1769-73.
          View in: PubMed
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