Michael Grabe, PhD

Professor

Cardiovascular Research Institute

Elisabeth Fall

[email protected]

Phone: +1 415 502-2874

555 Mission Bay Blvd South, Rm 452T

UCSF Box 3122

San Francisco, CA 94158

United States

Links

Grabe Lab UCSF Profiles

Affiliations

What I do

My lab uses computational methods to understand biological phenomena. We are primarily interested in ion 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.

Departmental research area

computational biology and chemistry

physical biology

My research expertise

membrane channels and transporters, molecular simulation, continuum electrostatics and elasticity theory

Professional background

Biography

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.

Research keywords

Ion Channel Gating
Vacuolar Proton-Translocating ATPases
Static Electricity
Sodium
Artificial Membranes
Molecular Dynamics Simulation
Protons
Viral Matrix Proteins
Symporters
Sodium-Glucose Transport Proteins
Organelles
Cell Membrane
Lipid Bilayers
Voltage-Dependent Anion Channel 1
Biological Models

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

Publications

Stephens CA, van Hilten N, Zheng L, Grabe M. Robust lipid scrambling by TMEM16 proteins requires an open groove and thin membrane. bioRxiv. 2024 Sep 27.

Lincoff J, Helsell CVM, Marcoline FV, Natale AM, Grabe M. Membrane curvature sensing and symmetry breaking of the M2 proton channel from Influenza A. Elife. 2024 Aug 16; 13.

Yang H, Zingaro VA, Lincoff J, Tom H, Oikawa S, Oses-Prieto JA, Edmondson Q, Seiple I, Shah H, Kajimura S, Burlingame AL, Grabe M, Ruggero D. Remodelling of the translatome controls diet and its impact on tumorigenesis. Nature. 2024 Sep; 633(8028):189-197.

Roy-Chowdhury S, Jang S, Abderemane-Ali F, Naughton F, Grabe M, Minor DL. Structure of the human K2P13.1(THIK-1) channel reveals a novel hydrophilic pore restriction and lipid cofactor site. bioRxiv. 2024 Jun 27.

Khan F, Elgeti M, Grandfield S, Paz A, Naughton FB, Marcoline FV, Althoff T, Ermolova N, Wright EM, Hubbell WL, Grabe M, Abramson J. Membrane potential accelerates sugar uptake by stabilizing the outward facing conformation of the Na/glucose symporter vSGLT. Nat Commun. 2023 11 18; 14(1):7511.

Moss FR, Lincoff J, Tucker M, Mohammed A, Grabe M, Frost A. Brominated lipid probes expose structural asymmetries in constricted membranes. Nat Struct Mol Biol. 2023 02; 30(2):167-175.

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. Regulation of the mammalian-brain V-ATPase through ultraslow mode-switching. Nature. 2022 11; 611(7937):827-834.

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. Quaternary structure independent folding of voltage-gated ion channel pore domain subunits. Nat Struct Mol Biol. 2022 06; 29(6):537-548.

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. Mitochondrial uncouplers induce proton leak by activating AAC and UCP1. Nature. 2022 06; 606(7912):180-187.

Marcoline FV, Furth J, Nayak S, Grabe M, Macey RI. Berkeley Madonna Version 10-A simulation package for solving mathematical models. CPT Pharmacometrics Syst Pharmacol. 2022 03; 11(3):290-301.

Gomez YK, Natale AM, Lincoff J, Wolgemuth CW, Rosenberg JM, Grabe M. Taking the Monte-Carlo gamble: How not to buckle under the pressure! J Comput Chem. 2022 03 05; 43(6):431-434.

Fong LK, Chalkley MJ, Tan SK, Grabe M, DeGrado WF. Elucidation of the molecular interactions that enable stable assembly and structural diversity in multicomponent immune receptors. Proc Natl Acad Sci U S A. 2021 06 29; 118(26).

Stockbridge RB, Gaudet R, Grabe M, Minor DL. Inroads into Membrane Physiology through Transport Nanomachines. J Mol Biol. 2021 08 06; 433(16):167101.

Chin MY, Patwardhan AR, Ang KH, Wang AL, Alquezar C, Welch M, Nguyen PT, Grabe M, Molofsky AV, Arkin MR, Kao AW. Genetically Encoded, pH-Sensitive mTFP1 Biosensor for Probing Lysosomal pH. ACS Sens. 2021 06 25; 6(6):2168-2180.

Pirro F, Schmidt N, Lincoff J, Widel ZX, Polizzi NF, Liu L, Therien MJ, Grabe M, Chino M, Lombardi A, DeGrado WF. Allosteric cooperation in a de novo-designed two-domain protein. Proc Natl Acad Sci U S A. 2020 12 29; 117(52):33246-33253.

Lolicato M, Natale AM, Abderemane-Ali F, Crottès D, Capponi S, Duman R, Wagner A, Rosenberg JM, Grabe M, Minor DL. K2P channel C-type gating involves asymmetric selectivity filter order-disorder transitions. Sci Adv. 2020 10; 6(44).

Zhou YC, Argudo D, Marcoline F, Grabe M. A Computational Model of Protein Induced Membrane Morphology with Geodesic Curvature Driven Protein-Membrane Interface. J Comput Phys. 2020 Dec 01; 422.

Bisignano P, Lee MA, George A, Zuckerman DM, Grabe M, Rosenberg JM. A kinetic mechanism for enhanced selectivity of membrane transport. PLoS Comput Biol. 2020 07; 16(7):e1007789.

George A, Bisignano P, Rosenberg JM, Grabe M, Zuckerman DM. A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms. PLoS Comput Biol. 2020 07; 16(7):e1007884.

Grabe M, Zuckerman DM, Rosenberg JM. EmrE reminds us to expect the unexpected in membrane transport. J Gen Physiol. 2020 01 06; 152(1).

Singh A, Marcoline FV, Veshaguri S, Kao AW, Bruchez M, Mindell JA, Stamou D, Grabe M. Protons in small spaces: Discrete simulations of vesicle acidification. PLoS Comput Biol. 2019 12; 15(12):e1007539.

Igoshin OA, Chen J, Xing J, Liu J, Elston TC, Grabe M, Kim KS, Nirody JA, Rangamani P, Sun SX, Wang H, Wolgemuth C. Biophysics at the coffee shop: lessons learned working with George Oster. Mol Biol Cell. 2019 07 22; 30(16):1882-1889.

Guerriero CJ, Gomez YK, Daskivich GJ, Reutter KR, Augustine AA, Weiberth KF, Nakatsukasa K, Grabe M, Brodsky JL. Harmonizing Experimental Data with Modeling to Predict Membrane Protein Insertion in Yeast. Biophys J. 2019 08 20; 117(4):668-678.

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 03 04; 151(3):316-327.

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.

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.

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 10 18; 72(2):316-327.e5.

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 10 02; 57(39):5748-5758.

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.

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.

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 03 07; 97(5):1063-1077.e4.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Ishida Y, Nayak S, Mindell JA, Grabe M. A model of lysosomal pH regulation. J Gen Physiol. 2013 Jun; 141(6):705-20.

Adelman JL, Grabe M. Simulating rare events using a weighted ensemble-based string method. J Chem Phys. 2013 Jan 28; 138(4):044105.

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.

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.

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).

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.

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 α subunit reveals a mechanism of channel activation by proteases. J Biol Chem. 2011 Jan 07; 286(1):649-60.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Lecar H, Larsson HP, Grabe M. Electrostatic model of S4 motion in voltage-gated ion channels. Biophys J. 2003 Nov; 85(5):2854-64.

Cohen BE, Grabe M, Jan LY. Answers and questions from the KvAP structures. Neuron. 2003 Jul 31; 39(3):395-400.

Grabe M, Neu J, Oster G, Nollert P. Protein interactions and membrane geometry. Biophys J. 2003 Feb; 84(2 Pt 1):854-68.

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.

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.

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.

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.

Grabe M, Oster G. Regulation of organelle acidity. J Gen Physiol. 2001 Apr; 117(4):329-44.

Grabe M, Wang H, Oster G. The mechanochemistry of V-ATPase proton pumps. Biophys J. 2000 Jun; 78(6):2798-813.

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.

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.

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.