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profileJoseph Avruch, M.D.

TitleProfessor of Medicine
InstitutionMassachusetts General Hospital
DepartmentMedicine
AddressMassachusetts General Hospital
Richard B. Simches Bldg., Diabetes Rsch. Labs, Rm 6.408
185 Cambridge St
Boston MA 02114
Phone617/726-6909
Fax617/726-5649
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Collapse Research 
Collapse research activities and funding
The research activities and funding listed below are automatically derived from NIH ExPORTER and other sources, which might result in incorrect or missing items. Faculty can login to make corrections and additions.
S10OD020112     (AVRUCH, JOSEPH)Feb 19, 2015 - Feb 18, 2016
NIH
TSE Systems Phenomaster Indirect Calorimetry Apparatus
Role: Principal Investigator

R01CA136567     (AVRUCH, JOSEPH)Jul 6, 2010 - Apr 30, 2015
NIH/NCI
Decoding the MST1 and MST2 kinases in cellular physiology and tumor suppression
Role: Principal Investigator

P30DK057521     (AVRUCH, JOSEPH)Jun 1, 2000 - Mar 31, 2020
NIH/NIDDK
Boston Area Diabetes Endocrinology Research Center
Role: Principal Investigator

R01CA073818     (AVRUCH, JOSEPH)Apr 1, 1997 - Nov 30, 2012
NIH/NCI
Molecular basis of Cell Growth Control by the TOR kinase
Role: Principal Investigator

R13GM051459     (AVRUCH, JOSEPH)Jun 13, 1994 - Jun 12, 1995
NIH/NIGMS
CONFERENCE ON 2ND MESSENGERS AND PROTEIN PHOSPHORYLATION
Role: Principal Investigator

Collapse Bibliographic 
Collapse selected publications
Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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  1. Galan JA, Avruch J. MST1/MST2 Protein Kinases: Regulation and Physiologic Roles. Biochemistry. 2016 Oct 04; 55(39):5507-5519. PMID: 27618557.
    View in: PubMed
  2. Geng J, Sun X, Wang P, Zhang S, Wang X, Wu H, Hong L, Xie C, Li X, Zhao H, Liu Q, Jiang M, Chen Q, Zhang J, Li Y, Song S, Wang HR, Zhou R, Johnson RL, Chien KY, Lin SC, Han J, Avruch J, Chen L, Zhou D. Kinases Mst1 and Mst2 positively regulate phagocytic induction of reactive oxygen species and bactericidal activity. Nat Immunol. 2015 Nov; 16(11):1142-52. PMID: 26414765; PMCID: PMC4618176.
  3. Dai N, Zhao L, Wrighting D, Krämer D, Majithia A, Wang Y, Cracan V, Borges-Rivera D, Mootha VK, Nahrendorf M, Thorburn DR, Minichiello L, Altshuler D, Avruch J. IGF2BP2/IMP2-Deficient mice resist obesity through enhanced translation of Ucp1 mRNA and Other mRNAs encoding mitochondrial proteins. Cell Metab. 2015 Apr 07; 21(4):609-21. PMID: 25863250; PMCID: PMC4663978.
  4. Papageorgiou A, Rapley J, Mesirov JP, Tamayo P, Avruch J. A genome-wide siRNA screen in mammalian cells for regulators of S6 phosphorylation. PLoS One. 2015; 10(3):e0116096. PMID: 25790369; PMCID: PMC4366019.
  5. Fitamant J, Kottakis F, Benhamouche S, Tian HS, Chuvin N, Parachoniak CA, Nagle JM, Perera RM, Lapouge M, Deshpande V, Zhu AX, Lai A, Min B, Hoshida Y, Avruch J, Sia D, Campreciós G, McClatchey AI, Llovet JM, Morrissey D, Raj L, Bardeesy N. YAP Inhibition Restores Hepatocyte Differentiation in Advanced HCC, Leading to Tumor Regression. Cell Rep. 2015 Mar 10. PMID: 25772357.
    View in: PubMed
  6. Oshiro N, Rapley J, Avruch J. Amino acids activate mammalian target of rapamycin (mTOR) complex 1 without changing Rag GTPase guanyl nucleotide charging. J Biol Chem. 2014 Jan 31; 289(5):2658-74. PMID: 24337580; PMCID: PMC3908400.
  7. Wu H, Xiao Y, Zhang S, Ji S, Wei L, Fan F, Geng J, Tian J, Sun X, Qin F, Jin C, Lin J, Yin ZY, Zhang T, Luo L, Li Y, Song S, Lin SC, Deng X, Camargo F, Avruch J, Chen L, Zhou D. The Ets transcription factor GABP is a component of the hippo pathway essential for growth and antioxidant defense. Cell Rep. 2013 May 30; 3(5):1663-77. PMID: 23684612; PMCID: PMC3855275.
  8. Regué L, Mou F, Avruch J. G protein-coupled receptors engage the mammalian Hippo pathway through F-actin: F-Actin, assembled in response to Galpha12/13 induced RhoA-GTP, promotes dephosphorylation and activation of the YAP oncogene. Bioessays. 2013 May; 35(5):430-5. PMID: 23450633; PMCID: PMC4092039.
  9. Gao T, Zhou D, Yang C, Singh T, Penzo-Méndez A, Maddipati R, Tzatsos A, Bardeesy N, Avruch J, Stanger BZ. Hippo signaling regulates differentiation and maintenance in the exocrine pancreas. Gastroenterology. 2013 Jun; 144(7):1543-53, 1553.e1. PMID: 23454691; PMCID: PMC3665616.
  10. Dai N, Christiansen J, Nielsen FC, Avruch J. mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts. Genes Dev. 2013 Feb 01; 27(3):301-12. PMID: 23388827; PMCID: PMC3576515.
  11. Avruch J, Zhou D, Fitamant J, Bardeesy N, Mou F, Barrufet LR. Protein kinases of the Hippo pathway: regulation and substrates. Semin Cell Dev Biol. 2012 Sep; 23(7):770-84. PMID: 22898666; PMCID: PMC3489012.
  12. Faustman DL, Wang L, Okubo Y, Burger D, Ban L, Man G, Zheng H, Schoenfeld D, Pompei R, Avruch J, Nathan DM. Proof-of-concept, randomized, controlled clinical trial of Bacillus-Calmette-Guerin for treatment of long-term type 1 diabetes. PLoS One. 2012; 7(8):e41756. PMID: 22905105; PMCID: PMC3414482.
  13. Chen L, Qin F, Deng X, Avruch J, Zhou D. Hippo pathway in intestinal homeostasis and tumorigenesis. Protein Cell. 2012 Apr; 3(4):305-10. PMID: 22492181; PMCID: PMC4875478.
  14. Kyriakis JM, Avruch J. Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. Physiol Rev. 2012 Apr; 92(2):689-737. PMID: 22535895.
    View in: PubMed
  15. Avruch J, Zhou D, Bardeesy N. YAP oncogene overexpression supercharges colon cancer proliferation. Cell Cycle. 2012 Mar 15; 11(6):1090-6. PMID: 22356765; PMCID: PMC3335916.
  16. Mou F, Praskova M, Xia F, Van Buren D, Hock H, Avruch J, Zhou D. The Mst1 and Mst2 kinases control activation of rho family GTPases and thymic egress of mature thymocytes. J Exp Med. 2012 Apr 09; 209(4):741-59. PMID: 22412158; PMCID: PMC3328371.
  17. Papageorgiou A, Avruch J. A genome-wide RNAi screen for polypeptides that alter rpS6 phosphorylation. Methods Mol Biol. 2012; 821:187-214. PMID: 22125066; PMCID: PMC3535007.
  18. Zhou D, Zhang Y, Wu H, Barry E, Yin Y, Lawrence E, Dawson D, Willis JE, Markowitz SD, Camargo FD, Avruch J. Mst1 and Mst2 protein kinases restrain intestinal stem cell proliferation and colonic tumorigenesis by inhibition of Yes-associated protein (Yap) overabundance. Proc Natl Acad Sci U S A. 2011 Dec 06; 108(49):E1312-20. PMID: 22042863; PMCID: PMC3241824.
  19. Rapley J, Oshiro N, Ortiz-Vega S, Avruch J. The mechanism of insulin-stimulated 4E-BP protein binding to mammalian target of rapamycin (mTOR) complex 1 and its contribution to mTOR complex 1 signaling. J Biol Chem. 2011 Nov 04; 286(44):38043-53. PMID: 21914810; PMCID: PMC3207408.
  20. Bertran MT, Sdelci S, Regué L, Avruch J, Caelles C, Roig J. Nek9 is a Plk1-activated kinase that controls early centrosome separation through Nek6/7 and Eg5. EMBO J. 2011 Jun 03; 30(13):2634-47. PMID: 21642957; PMCID: PMC3155310.
  21. Dai N, Rapley J, Angel M, Yanik MF, Blower MD, Avruch J. mTOR phosphorylates IMP2 to promote IGF2 mRNA translation by internal ribosomal entry. Genes Dev. 2011 Jun 01; 25(11):1159-72. PMID: 21576258; PMCID: PMC3110954.
  22. Schlegelmilch K, Mohseni M, Kirak O, Pruszak J, Rodriguez JR, Zhou D, Kreger BT, Vasioukhin V, Avruch J, Brummelkamp TR, Camargo FD. Yap1 acts downstream of a-catenin to control epidermal proliferation. Cell. 2011 Mar 04; 144(5):782-95. PMID: 21376238; PMCID: PMC3237196.
  23. Avruch J, Zhou D, Fitamant J, Bardeesy N. Mst1/2 signalling to Yap: gatekeeper for liver size and tumour development. Br J Cancer. 2011 Jan 04; 104(1):24-32. PMID: 21102585; PMCID: PMC3039822.
  24. Park J, Kang SI, Lee SY, Zhang XF, Kim MS, Beers LF, Lim DS, Avruch J, Kim HS, Lee SB. Tumor suppressor ras association domain family 5 (RASSF5/NORE1) mediates death receptor ligand-induced apoptosis. J Biol Chem. 2010 Nov 05; 285(45):35029-38. PMID: 20810663; PMCID: PMC2966117.
  25. Zhou D, Conrad C, Xia F, Park JS, Payer B, Yin Y, Lauwers GY, Thasler W, Lee JT, Avruch J, Bardeesy N. Mst1 and Mst2 maintain hepatocyte quiescence and suppress hepatocellular carcinoma development through inactivation of the Yap1 oncogene. Cancer Cell. 2009 Nov 06; 16(5):425-38. PMID: 19878874; PMCID: PMC3023165.
  26. Lin Y, Avruch J. pTOM, a vector for expressing two proteins in mammalian cells. Anal Biochem. 2009 May 15; 388(2):353-5. PMID: 19303393; PMCID: PMC3197823.
  27. Avruch J, Long X, Lin Y, Ortiz-Vega S, Rapley J, Papageorgiou A, Oshiro N, Kikkawa U. Activation of mTORC1 in two steps: Rheb-GTP activation of catalytic function and increased binding of substrates to raptor. Biochem Soc Trans. 2009 Feb; 37(Pt 1):223-6. PMID: 19143636.
    View in: PubMed
  28. Avruch J, Xavier R, Bardeesy N, Zhang XF, Praskova M, Zhou D, Xia F. Rassf family of tumor suppressor polypeptides. J Biol Chem. 2009 Apr 24; 284(17):11001-5. PMID: 19091744; PMCID: PMC2670104.
  29. Zhou D, Medoff BD, Chen L, Li L, Zhang XF, Praskova M, Liu M, Landry A, Blumberg RS, Boussiotis VA, Xavier R, Avruch J. The Nore1B/Mst1 complex restrains antigen receptor-induced proliferation of naïve T cells. Proc Natl Acad Sci U S A. 2008 Dec 23; 105(51):20321-6. PMID: 19073936.
    View in: PubMed
  30. Patursky-Polischuk I, Stolovich-Rain M, Hausner-Hanochi M, Kasir J, Cybulski N, Avruch J, Rüegg MA, Hall MN, Meyuhas O. The TSC-mTOR pathway mediates translational activation of TOP mRNAs by insulin largely in a raptor- or rictor-independent manner. Mol Cell Biol. 2009 Feb; 29(3):640-9. PMID: 19047368; PMCID: PMC2630691.
  31. Rapley J, Nicolàs M, Groen A, Regué L, Bertran MT, Caelles C, Avruch J, Roig J. The NIMA-family kinase Nek6 phosphorylates the kinesin Eg5 at a novel site necessary for mitotic spindle formation. J Cell Sci. 2008 Dec 01; 121(Pt 23):3912-21. PMID: 19001501; PMCID: PMC4066659.
  32. Anguera MC, Liu M, Avruch J, Lee JT. Characterization of two Mst1-deficient mouse models. Dev Dyn. 2008 Nov; 237(11):3424-34. PMID: 18942145; PMCID: PMC2596583.
  33. Avruch J, Long X, Ortiz-Vega S, Rapley J, Papageorgiou A, Dai N. Amino acid regulation of TOR complex 1. Am J Physiol Endocrinol Metab. 2009 Apr; 296(4):E592-602. PMID: 18765678; PMCID: PMC2670622.
  34. Hagan GN, Lin Y, Magnuson MA, Avruch J, Czech MP. A Rictor-Myo1c complex participates in dynamic cortical actin events in 3T3-L1 adipocytes. Mol Cell Biol. 2008 Jul; 28(13):4215-26. PMID: 18426911; PMCID: PMC2447144.
  35. Praskova M, Xia F, Avruch J. MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation. Curr Biol. 2008 Mar 11; 18(5):311-21. PMID: 18328708.
    View in: PubMed
  36. Oshiro N, Takahashi R, Yoshino K, Tanimura K, Nakashima A, Eguchi S, Miyamoto T, Hara K, Takehana K, Avruch J, Kikkawa U, Yonezawa K. The proline-rich Akt substrate of 40 kDa (PRAS40) is a physiological substrate of mammalian target of rapamycin complex 1. J Biol Chem. 2007 Jul 13; 282(28):20329-39. PMID: 17517883; PMCID: PMC3199301.
  37. Long X, Lin Y, Ortiz-Vega S, Busch S, Avruch J. The Rheb switch 2 segment is critical for signaling to target of rapamycin complex 1. J Biol Chem. 2007 Jun 22; 282(25):18542-51. PMID: 17470430; PMCID: PMC3205911.
  38. Avruch J. MAP kinase pathways: the first twenty years. Biochim Biophys Acta. 2007 Aug; 1773(8):1150-60. PMID: 17229475; PMCID: PMC2043147.
  39. Avruch J, Hara K, Lin Y, Liu M, Long X, Ortiz-Vega S, Yonezawa K. Insulin and amino-acid regulation of mTOR signaling and kinase activity through the Rheb GTPase. Oncogene. 2006 Oct 16; 25(48):6361-72. PMID: 17041622.
    View in: PubMed
  40. Avruch J, Praskova M, Ortiz-Vega S, Liu M, Zhang XF. Nore1 and RASSF1 regulation of cell proliferation and of the MST1/2 kinases. Methods Enzymol. 2006; 407:290-310. PMID: 16757333.
    View in: PubMed
  41. Lenz G, Avruch J. Glutamatergic regulation of the p70S6 kinase in primary mouse neurons. J Biol Chem. 2005 Nov 18; 280(46):38121-4. PMID: 16183639.
    View in: PubMed
  42. Zhu J, Balan V, Bronisz A, Balan K, Sun H, Leicht DT, Luo Z, Qin J, Avruch J, Tzivion G. Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding. Mol Biol Cell. 2005 Oct; 16(10):4733-44. PMID: 16093354; PMCID: PMC1237079.
  43. Roig J, Groen A, Caldwell J, Avruch J. Active Nercc1 protein kinase concentrates at centrosomes early in mitosis and is necessary for proper spindle assembly. Mol Biol Cell. 2005 Oct; 16(10):4827-40. PMID: 16079175; PMCID: PMC1237086.
  44. Long X, Ortiz-Vega S, Lin Y, Avruch J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem. 2005 Jun 24; 280(25):23433-6. PMID: 15878852.
    View in: PubMed
  45. Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol. 2005 Apr 26; 15(8):702-13. PMID: 15854902.
    View in: PubMed
  46. Avruch J, Lin Y, Long X, Murthy S, Ortiz-Vega S. Recent advances in the regulation of the TOR pathway by insulin and nutrients. Curr Opin Clin Nutr Metab Care. 2005 Jan; 8(1):67-72. PMID: 15586002.
    View in: PubMed
  47. Praskova M, Khoklatchev A, Ortiz-Vega S, Avruch J. Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras. Biochem J. 2004 Jul 15; 381(Pt 2):453-62. PMID: 15109305; PMCID: PMC1133852.
  48. Aoyama Y, Avruch J, Zhang XF. Nore1 inhibits tumor cell growth independent of Ras or the MST1/2 kinases. Oncogene. 2004 Apr 22; 23(19):3426-33. PMID: 15007383.
    View in: PubMed
  49. Rabizadeh S, Xavier RJ, Ishiguro K, Bernabeortiz J, Lopez-Ilasaca M, Khokhlatchev A, Mollahan P, Pfeifer GP, Avruch J, Seed B. The scaffold protein CNK1 interacts with the tumor suppressor RASSF1A and augments RASSF1A-induced cell death. J Biol Chem. 2004 Jul 09; 279(28):29247-54. PMID: 15075335.
    View in: PubMed
  50. Oshiro N, Yoshino K, Hidayat S, Tokunaga C, Hara K, Eguchi S, Avruch J, Yonezawa K. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells. 2004 Apr; 9(4):359-66. PMID: 15066126.
    View in: PubMed
  51. Shen YH, Godlewski J, Bronisz A, Zhu J, Comb MJ, Avruch J, Tzivion G. Significance of 14-3-3 self-dimerization for phosphorylation-dependent target binding. Mol Biol Cell. 2003 Nov; 14(11):4721-33. PMID: 14551260; PMCID: PMC266786.
  52. Belham C, Roig J, Caldwell JA, Aoyama Y, Kemp BE, Comb M, Avruch J. A mitotic cascade of NIMA family kinases. Nercc1/Nek9 activates the Nek6 and Nek7 kinases. J Biol Chem. 2003 Sep 12; 278(37):34897-909. PMID: 12840024.
    View in: PubMed
  53. Nojima H, Tokunaga C, Eguchi S, Oshiro N, Hidayat S, Yoshino K, Hara K, Tanaka N, Avruch J, Yonezawa K. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem. 2003 May 02; 278(18):15461-4. PMID: 12604610.
    View in: PubMed
  54. Lin Y, Khokhlatchev A, Figeys D, Avruch J. Death-associated protein 4 binds MST1 and augments MST1-induced apoptosis. J Biol Chem. 2002 Dec 13; 277(50):47991-8001. PMID: 12384512.
    View in: PubMed
  55. Long X, Spycher C, Han ZS, Rose AM, Müller F, Avruch J. TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation. Curr Biol. 2002 Sep 03; 12(17):1448-61. PMID: 12225660.
    View in: PubMed
  56. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002 Jul 26; 110(2):177-89. PMID: 12150926.
    View in: PubMed
  57. Roig J, Mikhailov A, Belham C, Avruch J. Nercc1, a mammalian NIMA-family kinase, binds the Ran GTPase and regulates mitotic progression. Genes Dev. 2002 Jul 01; 16(13):1640-58. PMID: 12101123; PMCID: PMC186374.
  58. Tommasi S, Dammann R, Jin SG, Zhang XF, Avruch J, Pfeifer GP. RASSF3 and NORE1: identification and cloning of two human homologues of the putative tumor suppressor gene RASSF1. Oncogene. 2002 Apr 18; 21(17):2713-20. PMID: 11965544.
    View in: PubMed
  59. Ortiz-Vega S, Khokhlatchev A, Nedwidek M, Zhang XF, Dammann R, Pfeifer GP, Avruch J. The putative tumor suppressor RASSF1A homodimerizes and heterodimerizes with the Ras-GTP binding protein Nore1. Oncogene. 2002 Feb 21; 21(9):1381-90. PMID: 11857081.
    View in: PubMed
  60. Khokhlatchev A, Rabizadeh S, Xavier R, Nedwidek M, Chen T, Zhang XF, Seed B, Avruch J. Identification of a novel Ras-regulated proapoptotic pathway. Curr Biol. 2002 Feb 19; 12(4):253-65. PMID: 11864565.
    View in: PubMed
  61. Wu S, Mikhailov A, Kallo-Hosein H, Hara K, Yonezawa K, Avruch J. Characterization of ubiquilin 1, an mTOR-interacting protein. Biochim Biophys Acta. 2002 Jan 30; 1542(1-3):41-56. PMID: 11853878.
    View in: PubMed
  62. Tzivion G, Avruch J. 14-3-3 proteins: active cofactors in cellular regulation by serine/threonine phosphorylation. J Biol Chem. 2002 Feb 01; 277(5):3061-4. PMID: 11709560.
    View in: PubMed
  63. Force T, Pombo CM, Avruch JA, Bonventre JV, Kyriakis JM. Stress-activated protein kinases in cardiovascular disease. Circ Res. 1996 Jun; 78(6):947-53. PMID: 8635244.
    View in: PubMed
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