Michael Grabe, PhD
Professor
Cardiovascular Research Inst
School of Medicine

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.

Awards

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• Shining Star Award (for community service), Oakland Planning and Development Corporation, Pittsburgh, PA, 2012
• Senior Vice Chancellor's Research Seminar, University of Pittsburgh, 2011
• CAREER Award, NSF, 2009-2014
• Alfred P. Sloan Research Fellow in Molecular Biology, Sloan Foundation, 2009-2011
• Outstanding Graduate Student Instructor, University of California, Berkeley, 1997-1998

Education & Training

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• Diversity, Equity, and Inclusion Champion Training University of California 07/2021

Websites

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• Grabe Lab (grabelab.org)
• Profile at physio.ucsf.edu (physio.ucsf.edu)

Grants and Projects

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• Ion permeation, lipid flipping, and membrane remodeling by TMEM16 proteins, NIH, 2021-2024
• Computational studies of sodium symporters, NIH, 2011-2021
• Computer simulations of lysosomal and osteoclast microphysiology, NIH, 2012-2015
• High Performance Computing for Biomedical Research, NIH, 1990-2013

Publications (77)

Top publication keywords:
Ion Channel GatingVacuolar Proton-Translocating ATPasesStatic ElectricitySodiumMembranes, ArtificialMolecular Dynamics SimulationProtonsSymportersSodium-Glucose Transport ProteinsSodium-Glucose Transporter 1OrganellesCell MembraneLipid BilayersVoltage-Dependent Anion Channel 1Models, Biological

• Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT.
  Nature communications 2023 Khan F, Elgeti M, Grandfield S, Paz A, Naughton FB, Marcoline FV, Althoff T, Ermolova N, Wright EM, Hubbell WL, Grabe M, Abramson J
• Brominated lipid probes expose structural asymmetries in constricted membranes.
  Nature structural & molecular biology 2023 Moss FR, Lincoff J, Tucker M, Mohammed A, Grabe M, Frost A
• Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching.
  Nature 2022 Kosmidis E, Shuttle CG, Preobraschenski J, Ganzella M, Johnson PJ, Veshaguri S, Holmkvist J, Møller MP, Marantos O, Marcoline F, Grabe M, Pedersen JL, Jahn R, Stamou D
• Quaternary structure independent folding of voltage-gated ion channel pore domain subunits.
  Nature structural & molecular biology 2022 Arrigoni C, Lolicato M, Shaya D, Rohaim A, Findeisen F, Fong LK, Colleran CM, Dominik P, Kim SS, Schuermann JP, DeGrado WF, Grabe M, Kossiakoff AA, Minor DL
• Mitochondrial uncouplers induce proton leak by activating AAC and UCP1.
  Nature 2022 Bertholet AM, Natale AM, Bisignano P, Suzuki J, Fedorenko A, Hamilton J, Brustovetsky T, Kazak L, Garrity R, Chouchani ET, Brustovetsky N, Grabe M, Kirichok Y

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• Berkeley Madonna Version 10-A simulation package for solving mathematical models.
  CPT: pharmacometrics & systems pharmacology 2022 Marcoline FV, Furth J, Nayak S, Grabe M, Macey RI
• Taking the Monte-Carlo gamble: How not to buckle under the pressure!
  Journal of computational chemistry 2021 Gomez YK, Natale AM, Lincoff J, Wolgemuth CW, Rosenberg JM, Grabe M
• Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors.
  Proceedings of the National Academy of Sciences of the United States of America 2021 Fong LK, Chalkley MJ, Tan SK, Grabe M, DeGrado WF
• Inroads into Membrane Physiology through Transport Nanomachines.
  Journal of molecular biology 2021 Stockbridge RB, Gaudet R, Grabe M, Minor DL
• Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH.
  ACS sensors 2021 Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW
• Allosteric cooperation in a de novo-designed two-domain protein.
  Proceedings of the National Academy of Sciences of the United States of America 2020 Pirro F, Schmidt N, Lincoff J, Widel ZX, Polizzi NF, Liu L, Therien MJ, Grabe M, Chino M, Lombardi A, DeGrado WF
• K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions.
  Science advances 2020 Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL
• A Computational Model of Protein Induced Membrane Morphology with Geodesic Curvature Driven Protein-Membrane Interface.
  Journal of computational physics 2020 Zhou YC, Argudo D, Marcoline F, Grabe M
• A kinetic mechanism for enhanced selectivity of membrane transport.
  PLoS computational biology 2020 Bisignano P, Lee MA, George A, Zuckerman DM, Grabe M, Rosenberg JM
• A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms.
  PLoS computational biology 2020 George A, Bisignano P, Rosenberg JM, Grabe M, Zuckerman DM
• EmrE reminds us to expect the unexpected in membrane transport.
  The Journal of general physiology 2020 Grabe M, Zuckerman DM, Rosenberg JM
• Protons in small spaces: Discrete simulations of vesicle acidification.
  PLoS computational biology 2019 Singh A, Marcoline FV, Veshaguri S, Kao AW, Bruchez M, Mindell JA, Stamou D, Grabe M
• Biophysics at the coffee shop: lessons learned working with George Oster.
  Molecular biology of the cell 2019 Igoshin OA, Chen J, Xing J, Liu J, Elston TC, Grabe M, Kim KS, Nirody JA, Rangamani P, Sun SX, Wang H, Wolgemuth C
• Harmonizing Experimental Data with Modeling to Predict Membrane Protein Insertion in Yeast.
  Biophysical journal 2019 Guerriero CJ, Gomez YK, Daskivich GJ, Reutter KR, Augustine AA, Weiberth KF, Nakatsukasa K, Grabe M, Brodsky JL
• A multiscale model of mechanotransduction by the ankyrin chains of the NOMPC channel.
  The Journal of general physiology 2019 Argudo D, Capponi S, Bethel NP, Grabe M
• Chemically induced vesiculation as a platform for studying TMEM16F activity.
  Proceedings of the National Academy of Sciences of the United States of America 2019 Han TW, Ye W, Bethel NP, Zubia M, Kim A, Li KH, Burlingame AL, Grabe M, Jan YN, Jan LY
• Inhibitor binding mode and allosteric regulation of Na+-glucose symporters.
  Nature communications 2018 Bisignano P, Ghezzi C, Jo H, Polizzi NF, Althoff T, Kalyanaraman C, Friemann R, Jacobson MP, Wright EM, Grabe M
• Cilia-Associated Oxysterols Activate Smoothened.
  Molecular cell 2018 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 …
• Entry from the Lipid Bilayer: A Possible Pathway for Inhibition of a Peptide G Protein-Coupled Receptor by a Lipophilic Small Molecule.
  Biochemistry 2018 Bokoch MP, Jo H, Valcourt JR, Srinivasan Y, Pan AC, Capponi S, Grabe M, Dror RO, Shaw DE, DeGrado WF, Coughlin SR
• Substrate-bound outward-open structure of a Na+-coupled sialic acid symporter reveals a new Na+ site.
  Nature communications 2018 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,…
• Conformational transitions of the sodium-dependent sugar transporter, vSGLT.
  Proceedings of the National Academy of Sciences of the United States of America 2018 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
• The Sixth Transmembrane Segment Is a Major Gating Component of the TMEM16A Calcium-Activated Chloride Channel.
  Neuron 2018 Peters CJ, Gilchrist JM, Tien J, Bethel NP, Qi L, Chen T, Wang L, Jan YN, Grabe M, Jan LY
• Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.
  Proceedings of the National Academy of Sciences of the United States of America 2017 Bergdoll LA, Lerch MT, Patrick JW, Belardo K, Altenbach C, Bisignano P, Laganowsky A, Grabe M, Hubbell WL, Abramson J
• Transmembrane helix hydrophobicity is an energetic barrier during the retrotranslocation of integral membrane ERAD substrates.
  Molecular biology of the cell 2017 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
• New Continuum Approaches for Determining Protein-Induced Membrane Deformations.
  Biophysical journal 2017 Argudo D, Bethel NP, Marcoline FV, Wolgemuth CW, Grabe M
• Atomistic insight into lipid translocation by a TMEM16 scramblase.
  Proceedings of the National Academy of Sciences of the United States of America 2016 Bethel NP, Grabe M
• A mathematical model of osteoclast acidification during bone resorption.
  Bone 2016 Marcoline FV, Ishida Y, Mindell JA, Nayak S, Grabe M
• Stochastic steps in secondary active sugar transport.
  Proceedings of the National Academy of Sciences of the United States of America 2016 Adelman JL, Ghezzi C, Bisignano P, Loo DD, Choe S, Abramson J, Rosenberg JM, Wright EM, Grabe M
• Direct observation of proton pumping by a eukaryotic P-type ATPase.
  Science (New York, N.Y.) 2016 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
• Continuum descriptions of membranes and their interaction with proteins: Towards chemically accurate models.
  Biochimica et biophysica acta 2016 Argudo D, Bethel NP, Marcoline FV, Grabe M
• Membrane Protein Properties Revealed through Data-Rich Electrostatics Calculations.
  Structure (London, England : 1993) 2015 Marcoline FV, Bethel N, Guerriero CJ, Brodsky JL, Grabe M
• Simulating Current-Voltage Relationships for a Narrow Ion Channel Using the Weighted Ensemble Method.
  Journal of chemical theory and computation 2015 Adelman JL, Grabe M
• WESTPA: an interoperable, highly scalable software package for weighted ensemble simulation and analysis.
  Journal of chemical theory and computation 2015 Zwier MC, Adelman JL, Kaus JW, Pratt AJ, Wong KF, Rego NB, Suárez E, Lettieri S, Wang DW, Grabe M, Zuckerman DM, Chong LT
• De novo design of a transmembrane Zn²⁺-transporting four-helix bundle.
  Science (New York, N.Y.) 2014 Joh NH, Wang T, Bhate MP, Acharya R, Wu Y, Grabe M, Hong M, Grigoryan G, DeGrado WF
• Structure-guided simulations illuminate the mechanism of ATP transport through VDAC1.
  Nature structural & molecular biology 2014 Choudhary OP, Paz A, Adelman JL, Colletier JP, Abramson J, Grabe M
• Cardiac BIN1 folds T-tubule membrane, controlling ion flux and limiting arrhythmia.
  Nature medicine 2014 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
• Continuum approaches to understanding ion and peptide interactions with the membrane.
  The Journal of membrane biology 2014 Latorraca NR, Callenberg KM, Boyle JP, Grabe M
• Structural determinants of water permeation through the sodium-galactose transporter vSGLT.
  Biophysical journal 2014 Adelman JL, Sheng Y, Choe S, Abramson J, Wright EM, Rosenberg JM, Grabe M
• Antibacterial membrane attack by a pore-forming intestinal C-type lectin.
  Nature 2013 Mukherjee S, Zheng H, Derebe MG, Callenberg KM, Partch CL, Rollins D, Propheter DC, Rizo J, Grabe M, Jiang QX, Hooper LV
• A model of lysosomal pH regulation.
  The Journal of general physiology 2013 Ishida Y, Nayak S, Mindell JA, Grabe M
• Simulating rare events using a weighted ensemble-based string method.
  The Journal of chemical physics 2013 Adelman JL, Grabe M
• Membrane bending is critical for the stability of voltage sensor segments in the membrane.
  The Journal of general physiology 2012 Callenberg KM, Latorraca NR, Grabe M
• Simulations of the alternating access mechanism of the sodium symporter Mhp1.
  Biophysical journal 2011 Adelman JL, Dale AL, Zwier MC, Bhatt D, Chong LT, Zuckerman DM, Grabe M
• Raw sewage harbors diverse viral populations.
  mBio 2011 Cantalupo PG, Calgua B, Zhao G, Hundesa A, Wier AD, Katz JP, Grabe M, Hendrix RW, Girones R, Wang D, Pipas JM
• The mechanism of sodium and substrate release from the binding pocket of vSGLT.
  Nature 2010 Watanabe A, Choe S, Chaptal V, Rosenberg JM, Wright EM, Grabe M, Abramson J
• Constraint-based, homology model of the extracellular domain of the epithelial Na+ channel α subunit reveals a mechanism of channel activation by proteases.
  The Journal of biological chemistry 2010 Kashlan OB, Adelman JL, Okumura S, Blobner BM, Zuzek Z, Hughey RP, Kleyman TR, Grabe M
• Water permeation through the sodium-dependent galactose cotransporter vSGLT.
  Biophysical journal 2010 Choe S, Rosenberg JM, Abramson J, Wright EM, Grabe M
• APBSmem: a graphical interface for electrostatic calculations at the membrane.
  PloS one 2010 Callenberg KM, Choudhary OP, de Forest GL, Gohara DW, Baker NA, Grabe M
• Characterization of the PCMBS-dependent modification of KCa3.1 channel gating.
  The Journal of general physiology 2010 Bailey MA, Grabe M, Devor DC
• Allosteric inhibition of the epithelial Na+ channel through peptide binding at peripheral finger and thumb domains.
  The Journal of biological chemistry 2010 Kashlan OB, Boyd CR, Argyropoulos C, Okumura S, Hughey RP, Grabe M, Kleyman TR
• The electrostatics of VDAC: implications for selectivity and gating.
  Journal of molecular biology 2009 Choudhary OP, Ujwal R, Kowallis W, Coalson R, Abramson J, Grabe M
• Conformational dynamics of the inner pore helix of voltage-gated potassium channels.
  The Journal of chemical physics 2009 Choe S, Grabe M
• A continuum method for determining membrane protein insertion energies and the problem of charged residues.
  The Journal of general physiology 2008 Choe S, Hecht KA, Grabe M
• Getting in sync with dimeric Eg5. Initiation and regulation of the processive run.
  The Journal of biological chemistry 2007 Krzysiak TC, Grabe M, Gilbert SP
• Structure prediction for the down state of a potassium channel voltage sensor.
  Nature 2006 Grabe M, Lai HC, Jain M, Jan YN, Jan LY
• Electrostatic interactions in the channel cavity as an important determinant of potassium channel selectivity.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Bichet D, Grabe M, Jan YN, Jan LY
• K+ channel selectivity depends on kinetic as well as thermodynamic factors.
  Proceedings of the National Academy of Sciences of the United States of America 2006 Grabe M, Bichet D, Qian X, Jan YN, Jan LY
• Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.
  Annals of internal medicine 2006 Nayak S, Olkin I, Liu H, Grabe M, Gould MK, Allen IE, Owens DK, Bravata DM
• The S4 voltage sensor packs against the pore domain in the KAT1 voltage-gated potassium channel.
  Neuron 2005 Lai HC, Grabe M, Jan YN, Jan LY
• A quantitative assessment of models for voltage-dependent gating of ion channels.
  Proceedings of the National Academy of Sciences of the United States of America 2004 Grabe M, Lecar H, Jan YN, Jan LY
• Electrostatic model of S4 motion in voltage-gated ion channels.
  Biophysical journal 2003 Lecar H, Larsson HP, Grabe M
• Answers and questions from the KvAP structures.
  Neuron 2003 Cohen BE, Grabe M, Jan LY
• Protein interactions and membrane geometry.
  Biophysical journal 2003 Grabe M, Neu J, Oster G, Nollert P
• Biosynthesis and secretion of pituitary hormones: dynamics and regulation.
  Archives of physiology and biochemistry 2002 Moore HP, Andresen JM, Eaton BA, Grabe M, Haugwitz M, Wu MM, Machen TE
• Proton leak and CFTR in regulation of Golgi pH in respiratory epithelial cells.
  American journal of physiology. Cell physiology 2001 Chandy G, Grabe M, Moore HP, Machen TE
• Cystic fibrosis transmembrane conductance regulator and H+ permeability in regulation of Golgi pH.
  JOP : Journal of the pancreas 2001 Machen TE, Chandy G, Wu M, Grabe M, Moore HP
• Mechanisms of pH regulation in the regulated secretory pathway.
  The Journal of biological chemistry 2001 Wu MM, Grabe M, Adams S, Tsien RY, Moore HP, Machen TE
• Regulation of organelle acidity.
  The Journal of general physiology 2001 Grabe M, Oster G
• The mechanochemistry of V-ATPase proton pumps.
  Biophysical journal 2000 Grabe M, Wang H, Oster G
• How Fo-ATPase generates rotary torque.
  Philosophical transactions of the Royal Society of London. Series B, Biological sciences 2000 Oster G, Wang H, Grabe M
• Energy transduction in the sodium F-ATPase of Propionigenium modestum.
  Proceedings of the National Academy of Sciences of the United States of America 1999 Dimroth P, Wang H, Grabe M, Oster G
• Pathways, pathway tubes, pathway docking, and propagators in electron transfer proteins.
  Journal of bioenergetics and biomembranes 1995 Curry WB, Grabe MD, Kurnikov IV, Skourtis SS, Beratan DN, Regan JJ, Aquino AJ, Beroza P, Onuchic JN