Michael Grabe, PhD

Title(s)Professor, Cardiovascular Research Inst
SchoolSchool of Medicine
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    Collapse Biography 
    Collapse Awards and Honors
    Oakland Planning and Development Corporation, Pittsburgh, PA2012Shining Star Award (for community service)
    University of Pittsburgh2011Senior Vice Chancellor's Research Seminar
    NSF2009  - 2014CAREER Award
    Sloan Foundation2009  - 2011Alfred P. Sloan Research Fellow in Molecular Biology
    University of California, Berkeley1997  - 1998Outstanding Graduate Student Instructor

    Collapse Overview 
    Collapse Overview
    The Grabe lab uses computational methods to understand biological phenomena. We are primarily interested in ion and small molecule transport across cellular membranes. We wish to understand the molecular workings of ion channels and transporters as well as how these proteins work together to regulate ion homeostasis in excitable cells and intracellular organelles such as the lysosome. We are also interested in the role that membrane proteins play in controlling the intrinsic shape of organelles.

    Collapse Research 
    Collapse Research Activities and Funding
    Computer simulations of lysosomal and osteoclast microphysiology
    NIH/NIGMS R21GM100224Sep 1, 2012 - Jul 31, 2014
    Role: Principal Investigator
    Computational studies of sodium symporters
    NIH/NIGMS R01GM089740Sep 30, 2011 - May 31, 2021
    Role: Principal Investigator
    High Performance Computing for Biomedical Research
    NIH P41RR006009Sep 1, 1990 - Jul 31, 2013
    Role: Co-Investigator

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    Collapse Bibliographic 
    Collapse Publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Researchers can login to make corrections and additions, or contact us for help.
    List All   |   Timeline
    1. Argudo D, Capponi S, Bethel NP, Grabe M. A multiscale model of mechanotransduction by the ankyrin chains of the NOMPC channel. J Gen Physiol. 2019 Mar 04; 151(3):316-327. PMID: 30728217.
      View in: PubMed
    2. Han TW, Ye W, Bethel NP, Zubia M, Kim A, Li KH, Burlingame AL, Grabe M, Jan YN, Jan LY. Chemically induced vesiculation as a platform for studying TMEM16F activity. Proc Natl Acad Sci U S A. 2019 01 22; 116(4):1309-1318. PMID: 30622179.
      View in: PubMed
    3. Bisignano P, Ghezzi C, Jo H, Polizzi NF, Althoff T, Kalyanaraman C, Friemann R, Jacobson MP, Wright EM, Grabe M. Inhibitor binding mode and allosteric regulation of Na+-glucose symporters. Nat Commun. 2018 12 07; 9(1):5245. PMID: 30532032.
      View in: PubMed
    4. Raleigh DR, Sever N, Choksi PK, Sigg MA, Hines KM, Thompson BM, Elnatan D, Jaishankar P, Bisignano P, Garcia-Gonzalo FR, Krup AL, Eberl M, Byrne EFX, Siebold C, Wong SY, Renslo AR, Grabe M, McDonald JG, Xu L, Beachy PA, Reiter JF. Cilia-Associated Oxysterols Activate Smoothened. Mol Cell. 2018 Oct 18; 72(2):316-327.e5. PMID: 30340023.
      View in: PubMed
    5. Bokoch MP, Jo H, Valcourt JR, Srinivasan Y, Pan AC, Capponi S, Grabe M, Dror RO, Shaw DE, DeGrado WF, Coughlin SR. Entry from the Lipid Bilayer: A Possible Pathway for Inhibition of a Peptide G Protein-Coupled Receptor by a Lipophilic Small Molecule. Biochemistry. 2018 Oct 02; 57(39):5748-5758. PMID: 30102523.
      View in: PubMed
    6. Wahlgren WY, Dunevall E, North RA, Paz A, Scalise M, Bisignano P, Bengtsson-Palme J, Goyal P, Claesson E, Caing-Carlsson R, Andersson R, Beis K, Nilsson UJ, Farewell A, Pochini L, Indiveri C, Grabe M, Dobson RCJ, Abramson J, Ramaswamy S, Friemann R. Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site. Nat Commun. 2018 05 01; 9(1):1753. PMID: 29717135.
      View in: PubMed
    7. Paz A, Claxton DP, Kumar JP, Kazmier K, Bisignano P, Sharma S, Nolte SA, Liwag TM, Nayak V, Wright EM, Grabe M, Mchaourab HS, Abramson J. Conformational transitions of the sodium-dependent sugar transporter, vSGLT. Proc Natl Acad Sci U S A. 2018 03 20; 115(12):E2742-E2751. PMID: 29507231.
      View in: PubMed
    8. Peters CJ, Gilchrist JM, Tien J, Bethel NP, Qi L, Chen T, Wang L, Jan YN, Grabe M, Jan LY. The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel. Neuron. 2018 Mar 07; 97(5):1063-1077.e4. PMID: 29478917.
      View in: PubMed
    9. Bergdoll LA, Lerch MT, Patrick JW, Belardo K, Altenbach C, Bisignano P, Laganowsky A, Grabe M, Hubbell WL, Abramson J. Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1. Proc Natl Acad Sci U S A. 2018 01 09; 115(2):E172-E179. PMID: 29279396.
      View in: PubMed
    10. Guerriero CJ, Reutter KR, Augustine AA, Preston GM, Weiberth KF, Mackie TD, Cleveland-Rubeor HC, Bethel NP, Callenberg KM, Nakatsukasa K, Grabe M, Brodsky JL. Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates. Mol Biol Cell. 2017 Jul 15; 28(15):2076-2090. PMID: 28539401.
      View in: PubMed
    11. Argudo D, Bethel NP, Marcoline FV, Wolgemuth CW, Grabe M. New Continuum Approaches for Determining Protein-Induced Membrane Deformations. Biophys J. 2017 May 23; 112(10):2159-2172. PMID: 28538153.
      View in: PubMed
    12. Bethel NP, Grabe M. Atomistic insight into lipid translocation by a TMEM16 scramblase. Proc Natl Acad Sci U S A. 2016 12 06; 113(49):14049-14054. PMID: 27872308.
      View in: PubMed
    13. Marcoline FV, Ishida Y, Mindell JA, Nayak S, Grabe M. A mathematical model of osteoclast acidification during bone resorption. Bone. 2016 12; 93:167-180. PMID: 27650914.
      View in: PubMed
    14. Adelman JL, Ghezzi C, Bisignano P, Loo DD, Choe S, Abramson J, Rosenberg JM, Wright EM, Grabe M. Stochastic steps in secondary active sugar transport. Proc Natl Acad Sci U S A. 2016 07 05; 113(27):E3960-6. PMID: 27325773; PMCID: PMC4941443 [Available on 01/05/17].
    15. Veshaguri S, Christensen SM, Kemmer GC, Ghale G, Møller MP, Lohr C, Christensen AL, Justesen BH, Jørgensen IL, Schiller J, Hatzakis NS, Grabe M, Pomorski TG, Stamou D. Direct observation of proton pumping by a eukaryotic P-type ATPase. Science. 2016 Mar 25; 351(6280):1469-73. PMID: 27013734.
      View in: PubMed
    16. Argudo D, Bethel NP, Marcoline FV, Grabe M. Continuum descriptions of membranes and their interaction with proteins: Towards chemically accurate models. Biochim Biophys Acta. 2016 Jul; 1858(7 Pt B):1619-34. PMID: 26853937.
      View in: PubMed
    17. Marcoline FV, Bethel N, Guerriero CJ, Brodsky JL, Grabe M. Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations. Structure. 2015 Aug 04; 23(8):1526-1537. PMID: 26118532.
      View in: PubMed
    18. Adelman JL, Grabe M. Simulating Current-Voltage Relationships for a Narrow Ion Channel Using the Weighted Ensemble Method. J Chem Theory Comput. 2015 Apr 14; 11(4):1907-18. PMID: 26392816; PMCID: PMC4573566.
    19. Zwier MC, Adelman JL, Kaus JW, Pratt AJ, Wong KF, Rego NB, Suárez E, Lettieri S, Wang DW, Grabe M, Zuckerman DM, Chong LT. WESTPA: an interoperable, highly scalable software package for weighted ensemble simulation and analysis. J Chem Theory Comput. 2015 Feb 10; 11(2):800-9. PMID: 26392815; PMCID: PMC4573570.
    20. Joh NH, Wang T, Bhate MP, Acharya R, Wu Y, Grabe M, Hong M, Grigoryan G, DeGrado WF. De novo design of a transmembrane Zn²?-transporting four-helix bundle. Science. 2014 Dec 19; 346(6216):1520-4. PMID: 25525248; PMCID: PMC4400864.
    21. Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M. Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1. Nat Struct Mol Biol. 2014 Jul; 21(7):626-32. PMID: 24908397; PMCID: PMC4157756.
    22. Hong T, Yang H, Zhang SS, Cho HC, Kalashnikova M, Sun B, Zhang H, Bhargava A, Grabe M, Olgin J, Gorelik J, Marbán E, Jan LY, Shaw RM. Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia. Nat Med. 2014 Jun; 20(6):624-32. PMID: 24836577; PMCID: PMC4048325.
    23. Latorraca NR, Callenberg KM, Boyle JP, Grabe M. Continuum approaches to understanding ion and peptide interactions with the membrane. J Membr Biol. 2014 May; 247(5):395-408. PMID: 24652510.
      View in: PubMed
    24. Adelman JL, Sheng Y, Choe S, Abramson J, Wright EM, Rosenberg JM, Grabe M. Structural determinants of water permeation through the sodium-galactose transporter vSGLT. Biophys J. 2014 Mar 18; 106(6):1280-9. PMID: 24655503; PMCID: PMC3984995.
    25. Mukherjee S, Zheng H, Derebe MG, Callenberg KM, Partch CL, Rollins D, Propheter DC, Rizo J, Grabe M, Jiang QX, Hooper LV. Antibacterial membrane attack by a pore-forming intestinal C-type lectin. Nature. 2014 Jan 02; 505(7481):103-7. PMID: 24256734; PMCID: PMC4160023.
    26. Ishida Y, Nayak S, Mindell JA, Grabe M. A model of lysosomal pH regulation. J Gen Physiol. 2013 Jun; 141(6):705-20. PMID: 23712550; PMCID: PMC3664703.
    27. Adelman JL, Grabe M. Simulating rare events using a weighted ensemble-based string method. J Chem Phys. 2013 Jan 28; 138(4):044105. PMID: 23387566; PMCID: PMC3568092.
    28. Callenberg KM, Latorraca NR, Grabe M. Membrane bending is critical for the stability of voltage sensor segments in the membrane. J Gen Physiol. 2012 Jul; 140(1):55-68. PMID: 22732310; PMCID: PMC3382720.
    29. Adelman JL, Dale AL, Zwier MC, Bhatt D, Chong LT, Zuckerman DM, Grabe M. Simulations of the alternating access mechanism of the sodium symporter Mhp1. Biophys J. 2011 Nov 16; 101(10):2399-407. PMID: 22098738; PMCID: PMC3218348.
    30. Cantalupo PG, Calgua B, Zhao G, Hundesa A, Wier AD, Katz JP, Grabe M, Hendrix RW, Girones R, Wang D, Pipas JM. Raw sewage harbors diverse viral populations. MBio. 2011; 2(5). PMID: 21972239; PMCID: PMC3187576.
    31. Watanabe A, Choe S, Chaptal V, Rosenberg JM, Wright EM, Grabe M, Abramson J. The mechanism of sodium and substrate release from the binding pocket of vSGLT. Nature. 2010 Dec 16; 468(7326):988-91. PMID: 21131949; PMCID: PMC3736980.
    32. Kashlan OB, Adelman JL, Okumura S, Blobner BM, Zuzek Z, Hughey RP, Kleyman TR, Grabe M. Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel a subunit reveals a mechanism of channel activation by proteases. J Biol Chem. 2011 Jan 07; 286(1):649-60. PMID: 20974852; PMCID: PMC3013024.
    33. Choe S, Rosenberg JM, Abramson J, Wright EM, Grabe M. Water permeation through the sodium-dependent galactose cotransporter vSGLT. Biophys J. 2010 Oct 06; 99(7):L56-8. PMID: 20923633.
      View in: PubMed
    34. Callenberg KM, Choudhary OP, de Forest GL, Gohara DW, Baker NA, Grabe M. APBSmem: a graphical interface for electrostatic calculations at the membrane. PLoS One. 2010 Sep 29; 5(9). PMID: 20949122; PMCID: PMC2947494.
    35. Bailey MA, Grabe M, Devor DC. Characterization of the PCMBS-dependent modification of KCa3.1 channel gating. J Gen Physiol. 2010 Oct; 136(4):367-87. PMID: 20837673; PMCID: PMC2947057.
    36. Kashlan OB, Boyd CR, Argyropoulos C, Okumura S, Hughey RP, Grabe M, Kleyman TR. Allosteric inhibition of the epithelial Na+ channel through peptide binding at peripheral finger and thumb domains. J Biol Chem. 2010 Nov 05; 285(45):35216-23. PMID: 20817728; PMCID: PMC2966135.
    37. Choudhary OP, Ujwal R, Kowallis W, Coalson R, Abramson J, Grabe M. The electrostatics of VDAC: implications for selectivity and gating. J Mol Biol. 2010 Feb 26; 396(3):580-92. PMID: 20005234; PMCID: PMC3736979.
    38. Choe S, Grabe M. Conformational dynamics of the inner pore helix of voltage-gated potassium channels. J Chem Phys. 2009 Jun 07; 130(21):215103. PMID: 19508102.
      View in: PubMed
    39. Choe S, Hecht KA, Grabe M. A continuum method for determining membrane protein insertion energies and the problem of charged residues. J Gen Physiol. 2008 Jun; 131(6):563-73. PMID: 18474636; PMCID: PMC2391250.
    40. Krzysiak TC, Grabe M, Gilbert SP. Getting in sync with dimeric Eg5. Initiation and regulation of the processive run. J Biol Chem. 2008 Jan 25; 283(4):2078-87. PMID: 18037705; PMCID: PMC2265775.
    41. Grabe M, Lai HC, Jain M, Jan YN, Jan LY. Structure prediction for the down state of a potassium channel voltage sensor. Nature. 2007 Feb 01; 445(7127):550-3. PMID: 17187053.
      View in: PubMed
    42. Grabe M, Bichet D, Qian X, Jan YN, Jan LY. K+ channel selectivity depends on kinetic as well as thermodynamic factors. Proc Natl Acad Sci U S A. 2006 Sep 26; 103(39):14361-6. PMID: 16983068; PMCID: PMC1570128.
    43. Bichet D, Grabe M, Jan YN, Jan LY. Electrostatic interactions in the channel cavity as an important determinant of potassium channel selectivity. Proc Natl Acad Sci U S A. 2006 Sep 26; 103(39):14355-60. PMID: 16983069; PMCID: PMC1570129.
    44. Nayak S, Olkin I, Liu H, Grabe M, Gould MK, Allen IE, Owens DK, Bravata DM. Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis. Ann Intern Med. 2006 Jun 06; 144(11):832-41. PMID: 16754925.
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    45. Lai HC, Grabe M, Jan YN, Jan LY. The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel. Neuron. 2005 Aug 04; 47(3):395-406. PMID: 16055063.
      View in: PubMed
    46. Grabe M, Lecar H, Jan YN, Jan LY. A quantitative assessment of models for voltage-dependent gating of ion channels. Proc Natl Acad Sci U S A. 2004 Dec 21; 101(51):17640-5. PMID: 15591352; PMCID: PMC539724.
    47. Lecar H, Larsson HP, Grabe M. Electrostatic model of S4 motion in voltage-gated ion channels. Biophys J. 2003 Nov; 85(5):2854-64. PMID: 14581190; PMCID: PMC1303566.
    48. Cohen BE, Grabe M, Jan LY. Answers and questions from the KvAP structures. Neuron. 2003 Jul 31; 39(3):395-400. PMID: 12895415.
      View in: PubMed
    49. Grabe M, Neu J, Oster G, Nollert P. Protein interactions and membrane geometry. Biophys J. 2003 Feb; 84(2 Pt 1):854-68. PMID: 12547769; PMCID: PMC1302665.
    50. Moore HP, Andresen JM, Eaton BA, Grabe M, Haugwitz M, Wu MM, Machen TE. Biosynthesis and secretion of pituitary hormones: dynamics and regulation. Arch Physiol Biochem. 2002 Apr; 110(1-2):16-25. PMID: 11935396.
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    51. Chandy G, Grabe M, Moore HP, Machen TE. Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells. Am J Physiol Cell Physiol. 2001 Sep; 281(3):C908-21. PMID: 11502568.
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    52. Machen TE, Chandy G, Wu M, Grabe M, Moore HP. Cystic fibrosis transmembrane conductance regulator and H+ permeability in regulation of Golgi pH. JOP. 2001 Jul; 2(4 Suppl):229-36. PMID: 11875264.
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    53. Wu MM, Grabe M, Adams S, Tsien RY, Moore HP, Machen TE. Mechanisms of pH regulation in the regulated secretory pathway. J Biol Chem. 2001 Aug 31; 276(35):33027-35. PMID: 11402049.
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    54. Grabe M, Oster G. Regulation of organelle acidity. J Gen Physiol. 2001 Apr; 117(4):329-44. PMID: 11279253; PMCID: PMC2217256.
    55. Grabe M, Wang H, Oster G. The mechanochemistry of V-ATPase proton pumps. Biophys J. 2000 Jun; 78(6):2798-813. PMID: 10827963; PMCID: PMC1300868.
    56. Oster G, Wang H, Grabe M. How Fo-ATPase generates rotary torque. Philos Trans R Soc Lond B Biol Sci. 2000 Apr 29; 355(1396):523-8. PMID: 10836505; PMCID: PMC1692753.
    57. Dimroth P, Wang H, Grabe M, Oster G. Energy transduction in the sodium F-ATPase of Propionigenium modestum. Proc Natl Acad Sci U S A. 1999 Apr 27; 96(9):4924-9. PMID: 10220395; PMCID: PMC21793.
    58. Curry WB, Grabe MD, Kurnikov IV, Skourtis SS, Beratan DN, Regan JJ, Aquino AJ, Beroza P, Onuchic JN. Pathways, pathway tubes, pathway docking, and propagators in electron transfer proteins. J Bioenerg Biomembr. 1995 Jun; 27(3):285-93. PMID: 8847342.
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