David A. Sinclair, Ph.D.

Associate Professor, Department of Pathology, Harvard Medical School

Contact Info

David Sinclair
Harvard Medical School
77 Avenue Louis Pasteur
Boston, MA, 02115
Mailstop: NRB, 954
Phone: 617-432-3931
Fax: 617-432-6225
david_sinclair@hms.harvard.edu

Assistant

Not Available.

DF/HCC Program Affiliation

Cancer Cell Biology

Research Abstract

Not Available.

Publications

Lamming DW, Wood JG, Sinclair DA.Small molecules that regulate lifespan: evidence for xenohormesis.Mol Microbiol 2004 Aug;53(4):1003-9.
15306006
Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D.Sirtuin activators mimic caloric restriction and delay ageing in metazoans.Nature 2004 Aug 5;430(7000):686-9.
15254550
Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA.Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase.Science 2004 Jul 16;305(5682):390-2.
15205477
Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA.Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.Mol Cell 2004 Mar 12;13(5):627-38.
15023334
Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME.Stress-dependent regulation of FOXO transcription factors by the SIRT1 dea
14976264
Anderson RM, Latorre-Esteves M, Neves AR, Lavu S, Medvedik O, Taylor C, Howitz KT, Santos H, Sinclair DA.Yeast life-span extension by calorie restriction is independent of NAD fluctuation.Science 2003 Dec 19;302(5653):2124-6.
14605207
Sinclair DA.Cell biology. An age of instability.Science 2003 Sep 26;301(5641):1859-60.
14512612
Bitterman KJ, Medvedik O, Sinclair DA.Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.Microbiol Mol Biol Rev 2003 Sep;67(3):376-99, table of contents.
12966141
Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA.Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.Nature 2003 Sep 11;425(6954):191-6.
12939617
Sinclair D.Is DNA cut out for a long life?.Sci Aging Knowledge Environ 2003 Apr 23;2003(16):PE8.
12844521
Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA.Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.Nature 2003 May 8;423(6936):181-5.
12736687
Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA.Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.J Biol Chem 2002 Nov 22;277(47):45099-107.
12297502
Sinclair DA.Paradigms and pitfalls of yeast longevity research.Mech Ageing Dev 2002 Apr 30;123(8):857-67.
12044934
Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA.Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels.J Biol Chem 2002 May 24;277(21):18881-90.
11884393
Mills KD, Sinclair DA, Guarente L.MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks.Cell 1999 May 28;97(5):609-20.
10367890
Johnson FB, Sinclair DA, Guarente L.Molecular biology of aging.Cell 1999 Jan 22;96(2):291-302.
9988222
Sinclair D, Mills K, Guarente L.Aging in Saccharomyces cerevisiae.Annu Rev Microbiol 1998;52:533-60.
9891807
Sinclair DA, Mills K, Guarente L.Molecular mechanisms of yeast aging.Trends Biochem Sci 1998 Apr;23(4):131-4.
9584615
Sinclair DA, Guarente L.Extrachromosomal rDNA circles--a cause of aging in yeast.Cell 1997 Dec 26;91(7):1033-42.
9428525
Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L.Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.Cell 1997 May 2;89(3):
9150138
Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA.The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.PLoS ONE 2008;3(4):
18414679
Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek M
18046409
Medvedik O, Lamming DW, Kim KD, Sinclair DA.MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.PLoS Biol 2007 Oct 2;5(10):e261.
17914901
Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA.Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.Cell 2007 Sep 21;130(6):1095-107.
17889652
Li Y, Yokota T, Gama V, Yoshida T, Gomez JA, Ishikawa K, Sasaguri H, Cohen HY, Sinclair DA, Mizusawa H, Matsuyama S.Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.Cell Death Differ 2007 Dec;14(12):2058-67.
17885668
Oberdoerffer P, Sinclair DA.The role of nuclear architecture in genomic instability and ageing.Nat Rev Mol Cell Biol 2007 Sep;8(9):692-702.
17700626
Syrzycka M, McEachern LA, Kinneard J, Prabhu K, Fitzpatrick K, Schulze S, Rawls JM, Lloyd VK, Sinclair DA, Honda BM.The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene.Genome 2007 Jun;50(6):548-56.
17632576
Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, Chini EN.The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity.FASEB J 2007 Nov;21(13):3629-39.
17585054
Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH.SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral scle
17581637
Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR, Diamond DM, Doolittle DJ, Dorato MA, Duke SO, Feinendegen L, Gardner DE, Hart RW, Hastings KL, Hayes AW, Hoffmann GR, Ives JA, Jawo
17459441
Wood JG, Sinclair DA.TPE or not TPE? It's no longer a question.Trends Pharmacol Sci 2002 Jan;23(1):1-4.
11804639
Cohen H, Sinclair DA.Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase.Proc Natl Acad Sci U S A 2001 Mar 13;98(6):3174-9.
11248051
Sinclair DA.Yeast aging research: recent advances and medical relevance.Cell Mol Life Sci 1999 Nov 30;56(9-10):807-16.
11212340
Ashrafi K, Sinclair D, Gordon JI, Guarente L.Passage through stationary phase advances replicative aging in Saccharomyces cerevisiae.Proc Natl Acad Sci U S A 1999 Aug 3;96(16):9100-5.
10430902
Hong SP, Piper MD, Sinclair DA, Dawes IW.Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae is mediated by a tetrahydrofolate-responsive protein binding to a glycine regulatory region including a core 5'-CTTCTT-3' motif.J Bio
10187845
Sinclair DA, Mills K, Guarente L.Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.Science 1997 Aug 29;277(5330):1313-6.
9271578
Sinclair DA, Hong SP, Dawes IW.Specific induction by glycine of the gene for the P-subunit of glycine decarboxylase from Saccharomyces cerevisiae.Mol Microbiol 1996 Feb;19(3):611-23.
8830251
Sinclair DA, Dawes IW.Genetics of the synthesis of serine from glycine and the utilization of glycine as sole nitrogen source by Saccharomyces cerevisiae.Genetics 1995 Aug;140(4):1213-22.
7498764
Sinclair DA, Dawes IW, Dickinson JR.Purification and characterization of the branched chain alpha-ketoacid dehydrogenase complex from Saccharomyces cerevisiae.Biochem Mol Biol Int 1993 Dec;31(5):911-22.
8136709

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DF/HCC Directory Login Update Member Profile Change Account Settings Applying for Membership Benefits Requirements Responsibilities	David A. Sinclair, Ph.D. Associate Professor, Department of Pathology, Harvard Medical School Contact Info David Sinclair Harvard Medical School 77 Avenue Louis Pasteur Boston, MA, 02115 Mailstop: NRB, 954 Phone: 617-432-3931 Fax: 617-432-6225 david_sinclair@hms.harvard.edu Assistant Not Available. DF/HCC Program Affiliation Cancer Cell Biology Research Abstract Not Available. Publications Lamming DW, Wood JG, Sinclair DA.Small molecules that regulate lifespan: evidence for xenohormesis.Mol Microbiol 2004 Aug;53(4):1003-9. 15306006 Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D.Sirtuin activators mimic caloric restriction and delay ageing in metazoans.Nature 2004 Aug 5;430(7000):686-9. 15254550 Cohen HY, Miller C, Bitterman KJ, Wall NR, Hekking B, Kessler B, Howitz KT, Gorospe M, de Cabo R, Sinclair DA.Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase.Science 2004 Jul 16;305(5682):390-2. 15205477 Cohen HY, Lavu S, Bitterman KJ, Hekking B, Imahiyerobo TA, Miller C, Frye R, Ploegh H, Kessler BM, Sinclair DA.Acetylation of the C terminus of Ku70 by CBP and PCAF controls Bax-mediated apoptosis.Mol Cell 2004 Mar 12;13(5):627-38. 15023334 Brunet A, Sweeney LB, Sturgill JF, Chua KF, Greer PL, Lin Y, Tran H, Ross SE, Mostoslavsky R, Cohen HY, Hu LS, Cheng HL, Jedrychowski MP, Gygi SP, Sinclair DA, Alt FW, Greenberg ME.Stress-dependent regulation of FOXO transcription factors by the SIRT1 dea 14976264 Anderson RM, Latorre-Esteves M, Neves AR, Lavu S, Medvedik O, Taylor C, Howitz KT, Santos H, Sinclair DA.Yeast life-span extension by calorie restriction is independent of NAD fluctuation.Science 2003 Dec 19;302(5653):2124-6. 14605207 Sinclair DA.Cell biology. An age of instability.Science 2003 Sep 26;301(5641):1859-60. 14512612 Bitterman KJ, Medvedik O, Sinclair DA.Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.Microbiol Mol Biol Rev 2003 Sep;67(3):376-99, table of contents. 12966141 Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA.Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan.Nature 2003 Sep 11;425(6954):191-6. 12939617 Sinclair D.Is DNA cut out for a long life?.Sci Aging Knowledge Environ 2003 Apr 23;2003(16):PE8. 12844521 Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Sinclair DA.Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae.Nature 2003 May 8;423(6936):181-5. 12736687 Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA.Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1.J Biol Chem 2002 Nov 22;277(47):45099-107. 12297502 Sinclair DA.Paradigms and pitfalls of yeast longevity research.Mech Ageing Dev 2002 Apr 30;123(8):857-67. 12044934 Anderson RM, Bitterman KJ, Wood JG, Medvedik O, Cohen H, Lin SS, Manchester JK, Gordon JI, Sinclair DA.Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels.J Biol Chem 2002 May 24;277(21):18881-90. 11884393 Mills KD, Sinclair DA, Guarente L.MEC1-dependent redistribution of the Sir3 silencing protein from telomeres to DNA double-strand breaks.Cell 1999 May 28;97(5):609-20. 10367890 Johnson FB, Sinclair DA, Guarente L.Molecular biology of aging.Cell 1999 Jan 22;96(2):291-302. 9988222 Sinclair D, Mills K, Guarente L.Aging in Saccharomyces cerevisiae.Annu Rev Microbiol 1998;52:533-60. 9891807 Sinclair DA, Mills K, Guarente L.Molecular mechanisms of yeast aging.Trends Biochem Sci 1998 Apr;23(4):131-4. 9584615 Sinclair DA, Guarente L.Extrachromosomal rDNA circles--a cause of aging in yeast.Cell 1997 Dec 26;91(7):1033-42. 9428525 Kennedy BK, Gotta M, Sinclair DA, Mills K, McNabb DS, Murthy M, Pak SM, Laroche T, Gasser SM, Guarente L.Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae.Cell 1997 May 2;89(3): 9150138 Firestein R, Blander G, Michan S, Oberdoerffer P, Ogino S, Campbell J, Bhimavarapu A, Luikenhuis S, de Cabo R, Fuchs C, Hahn WC, Guarente LP, Sinclair DA.The SIRT1 deacetylase suppresses intestinal tumorigenesis and colon cancer growth.PLoS ONE 2008;3(4): 18414679 Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek M 18046409 Medvedik O, Lamming DW, Kim KD, Sinclair DA.MSN2 and MSN4 link calorie restriction and TOR to sirtuin-mediated lifespan extension in Saccharomyces cerevisiae.PLoS Biol 2007 Oct 2;5(10):e261. 17914901 Yang H, Yang T, Baur JA, Perez E, Matsui T, Carmona JJ, Lamming DW, Souza-Pinto NC, Bohr VA, Rosenzweig A, de Cabo R, Sauve AA, Sinclair DA.Nutrient-sensitive mitochondrial NAD+ levels dictate cell survival.Cell 2007 Sep 21;130(6):1095-107. 17889652 Li Y, Yokota T, Gama V, Yoshida T, Gomez JA, Ishikawa K, Sasaguri H, Cohen HY, Sinclair DA, Mizusawa H, Matsuyama S.Bax-inhibiting peptide protects cells from polyglutamine toxicity caused by Ku70 acetylation.Cell Death Differ 2007 Dec;14(12):2058-67. 17885668 Oberdoerffer P, Sinclair DA.The role of nuclear architecture in genomic instability and ageing.Nat Rev Mol Cell Biol 2007 Sep;8(9):692-702. 17700626 Syrzycka M, McEachern LA, Kinneard J, Prabhu K, Fitzpatrick K, Schulze S, Rawls JM, Lloyd VK, Sinclair DA, Honda BM.The pink gene encodes the Drosophila orthologue of the human Hermansky-Pudlak syndrome 5 (HPS5) gene.Genome 2007 Jun;50(6):548-56. 17632576 Barbosa MT, Soares SM, Novak CM, Sinclair D, Levine JA, Aksoy P, Chini EN.The enzyme CD38 (a NAD glycohydrolase, EC 3.2.2.5) is necessary for the development of diet-induced obesity.FASEB J 2007 Nov;21(13):3629-39. 17585054 Kim D, Nguyen MD, Dobbin MM, Fischer A, Sananbenesi F, Rodgers JT, Delalle I, Baur JA, Sui G, Armour SM, Puigserver P, Sinclair DA, Tsai LH.SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral scle 17581637 Calabrese EJ, Bachmann KA, Bailer AJ, Bolger PM, Borak J, Cai L, Cedergreen N, Cherian MG, Chiueh CC, Clarkson TW, Cook RR, Diamond DM, Doolittle DJ, Dorato MA, Duke SO, Feinendegen L, Gardner DE, Hart RW, Hastings KL, Hayes AW, Hoffmann GR, Ives JA, Jawo 17459441 Wood JG, Sinclair DA.TPE or not TPE? It's no longer a question.Trends Pharmacol Sci 2002 Jan;23(1):1-4. 11804639 Cohen H, Sinclair DA.Recombination-mediated lengthening of terminal telomeric repeats requires the Sgs1 DNA helicase.Proc Natl Acad Sci U S A 2001 Mar 13;98(6):3174-9. 11248051 Sinclair DA.Yeast aging research: recent advances and medical relevance.Cell Mol Life Sci 1999 Nov 30;56(9-10):807-16. 11212340 Ashrafi K, Sinclair D, Gordon JI, Guarente L.Passage through stationary phase advances replicative aging in Saccharomyces cerevisiae.Proc Natl Acad Sci U S A 1999 Aug 3;96(16):9100-5. 10430902 Hong SP, Piper MD, Sinclair DA, Dawes IW.Control of expression of one-carbon metabolism genes of Saccharomyces cerevisiae is mediated by a tetrahydrofolate-responsive protein binding to a glycine regulatory region including a core 5'-CTTCTT-3' motif.J Bio 10187845 Sinclair DA, Mills K, Guarente L.Accelerated aging and nucleolar fragmentation in yeast sgs1 mutants.Science 1997 Aug 29;277(5330):1313-6. 9271578 Sinclair DA, Hong SP, Dawes IW.Specific induction by glycine of the gene for the P-subunit of glycine decarboxylase from Saccharomyces cerevisiae.Mol Microbiol 1996 Feb;19(3):611-23. 8830251 Sinclair DA, Dawes IW.Genetics of the synthesis of serine from glycine and the utilization of glycine as sole nitrogen source by Saccharomyces cerevisiae.Genetics 1995 Aug;140(4):1213-22. 7498764 Sinclair DA, Dawes IW, Dickinson JR.Purification and characterization of the branched chain alpha-ketoacid dehydrogenase complex from Saccharomyces cerevisiae.Biochem Mol Biol Int 1993 Dec;31(5):911-22. 8136709
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