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Scott C. Blanchard, PhD
Scott C. Blanchard, PhD

Scott C. Blanchard, PhD

Member, St. Jude Faculty

  • Single-molecule Imaging Center
  • Endowed Chair in Molecular Imaging



BA (Economics) – University of California, Davis, California
BS (Chemistry/Molecular Biology) – University of California, Santa Cruz, California
PhD (Biophysics) – Stanford University, Stanford, California

Research Interests

Research in the Blanchard laboratory focuses on examining structure-function relationships in macromolecular assemblies using genetic, biochemical, and spectroscopic techniques. Our mission is to develop novel approaches, including single-molecule fluorescence imaging methods, to elucidate the conformational and compositional processes critical to the functions of biological systems. The regulation of protein synthesis and ribosome biogenesis in development and disease, mechanisms of integral membrane protein signaling, and small-molecule interventions in infectious disease, are key focus areas. A principal goal of investigating this diversity of biology systems is to reveal regulatory paradigms that explain how cellular factors and small-molecules modify the function of essential molecular machines. We seek to leverage the information obtained from our discovery research initiatives to improve the efficacy of clinical interventions for the betterment of the human condition.

Selected Publications

Girodat D, Wieden HJ, Blanchard SC*, Sanbonmatsu KY*. Geometric alignment of aminoacyl-tRNA relative to catalytic centers of the ribosome underpins accurate mRNA decoding. Nat Commun Sep 11;14(1):5582, 2023. doi: 10.1038/s41467-023-40404-9. PMID: 37696823 (*co-corresponding authors)

Holm M, Natchiar SK, Rundlet EJ, Myasnikov AG, Watson ZL, Altman RB, Wang HY, Taunton J, Blanchard SC. mRNA decoding in human is kinetically and structurally distinct from bacteria. Nature May;617(7959):200-207, 2023. doi: 10.1038/s41586-023-05908-w. PMID: 37020024

Levring J, Terry DS, Kilic Z, Fitzgerald G, Blanchard SC*, Chen J*. CFTR function, pathology and pharmacology at single-molecule resolution. Nature Apr;616(7957):606-614, 2023. doi: 10.1038/s41586-023-05854-7. PMID: 36949202 (*co-corresponding authors)

Martin MI, Pati AK, Abeywickrama CS, Bar S, Kilic Z, Altman RB, Blanchard SC. Leveraging Baird aromaticity for advancement of bioimaging applications. J Phys Org Chem Jan;36(1):e4449, 2023. doi: 10.1002/poc.4449. PMID: 36590885

Nishima W, Girodat D, Holm M, Rundlet EJ, Alejo JL, Fischer K, Blanchard SC*, Sanbonmatsu KY*. Hyper-swivel head domain motions are required for complete mRNA-tRNA translocation and ribosome resetting. Nucleic Acids Res Aug 12;50(14):8302-8320, 2022. doi: 10.1093/nar/gkac597. PMID: 35808938 (*co-corresponding authors)

Juette MF, Carelli JD, Rundlet EJ, Brown A, Shao S, Ferguson A, Wasserman MR, Holm M, Taunton J*, Blanchard SC*. Didemnin B and ternatin-4 differentially inhibit conformational changes in eEF1A required for aminoacyl-tRNA accommodation into mammalian ribosomes. eLife Oct 20;11:e81608, 2022. doi:10.7554/eLife.81608 (*co-corresponding authors)

Asher WB, Terry DS, Gregorio GGA, Kahsai AW, Borgia A, Xie B, Modak A, Zhu Y, Jang W, Govindaraju A, Huang LY, Inoue A, Lambert NA, Gurevich VV, Shi L, Lefkowitz RJ, Blanchard SC*, Javitch JA*. GPCR-mediated β-arrestin activation deconvoluted with single-molecule precision. Cell May 12;185(10):1661-1675.e16, 2022. doi: 10.1016/j.cell.2022.03.042 (*co-corresponding authors)

Wieland M, Holm M, Rundlet EJ, Morici M, Koller TO, Maviza TP, Pogorevc D, Osterman IA, Müller R, Blanchard SC*, Wilson DN*. The cyclic octapeptide antibiotic argyrin B inhibits translation by trapping EF-G on the ribosome during translocation. Proc Natl Acad Sci U S A May 10;119(19):e2114214119.2022. doi:10.1073/pnas.2114214119 (*co-corresponding authors)

Rundlet EJ, Holm M, Schacherl M, Natchiar SK, Altman RB, Spahn CMT, Myasnikov AG, Blanchard SC. Structural basis of early translocation events on the ribosome. Nature Jul;595(7869):741-745, 2021. doi:10.1038/s41586-021-03713-x

Asher WB, Geggier P, Holsey MD, Gilmore GT, Pati AK, Meszaros J, Terry DS, Mathiasen S, Kaliszewski MJ, McCauley MD, Govindaraju A, Zhou Z, Harikumar KG, Jaqaman K, Miller LJ, Smith AW, Blanchard SC*, Javitch JA*. Single-molecule FRET imaging of GPCR dimers in living cells. Nat Methods Apr;18(4):397-405, 2021. doi:10.1038/s41592-021-01081-y. *Co-Corresponding Authors

Huysmans GHM, Ciftci D, Wang X, Blanchard SC, Boudker O. The high-energy transition state of the glutamate transporter homologue GltPh. EMBO J 40:e105415, 2021. doi: 10.15252/embj.2020105415

Lu M, Uchil PD, Li W, Zheng D, Terry DS, Gorman J, Shi W, Zhang B, Zhou T, Ding S, Gasser R, Prévost J, Beaudoin-Bussières G, Anand SP, Laumaea A, Grover JR, Liu L, Ho DD, Mascola JR, Finzi A, Kwong PD, Blanchard SC, Mothes W. Real-Time Conformational Dynamics of SARS-CoV-2 Spikes on Virus Particles. Cell Host Microbe 28:880-891.e8, 2020. doi: 10.1016/j.chom.2020.11.001

Pati AK, El Bakouri O, Jockusch S, Zhou Z, Altman RB, Fitzgerald GA, Asher WB, Terry DS, Borgia A, Holsey MD, Batchelder JE, Abeywickrama C, Huddle B, Rufa D, Javitch JA, Ottosson H, Blanchard SC. Tuning the Baird aromatic triplet-state energy of cyclooctatetraene to maximize the self-healing mechanism in organic fluorophores. Proc Natl Acad Sci USA 117:24305–24315, 2020. doi: 10.1073/pnas.2006517117

Li Z, Li W, Lu M, Bess J, Chao CW, Gorman J, Terry DS, Zhang B, Zhou T, Blanchard SC, Kwong PD, Lifson JD, Mothes W, Liu J. Subnanometer structures of HIV-1 envelope trimers on aldrithiol-2-inactivated virus particles. Nat Struct Mol Biol 27:726–734, 2020. doi: 10.1038/s41594-020-0452-2

Ciftci D, Huysmans GHM, Wang X, He C, Terry D, Zhou Z, Fitzgerald G, Blanchard SC*, Boudker O*. Single-molecule transport kinetics of a glutamate transporter homolog shows static disorder. Sci Adv 6:eaaz1949, 2020. doi: 10.1126/sciadv.aaz1949. *Co-Corresponding Authors

Gotfryd K, Boesen T, Mortensen JS, Khelashvili G, Quick M, Terry DS, Missel JW, LeVine MV, Gourdon P, Blanchard SC, Javitch JA, Weinstein H, Loland CJ, Nissen P, Gether U. X-ray structure of LeuT in an inward-facing occluded conformation reveals mechanism of substrate release. Nat Commun 11:1005, 2020. doi: 10.1038/s41467-020-14735-w

Morse JC, Girodat D, Burnett BJ, Holm M, Altman RB, Sanbonmatsu KY, Wieden H-J, Blanchard SC. Elongation factor-Tu can repetitively engage aminoacyl-tRNA within the ribosome during the proofreading stage of tRNA selection. Proc Natl Acad Sci USA 117:3610–3620, 2020. doi: 10.1073/pnas.1904469117

Henderson R, Lu M, Zhou Y, Mu Z, Parks R, Han Q, Hsu AL, Carter E, Blanchard SC, Edwards RJ, Wiehe K, Saunders KO, Borgnia MJ, Bartesaghi A, Mothes W, Haynes BF, Acharya P, Munir Alam S. Disruption of the HIV-1 Envelope allosteric network blocks CD4-induced rearrangements. Nat Commun 11:520, 2020. doi: 10.1038/s41467-019-14196-w

Fitzgerald GA, Terry DS, Warren AL, Quick M, Javitch JA, Blanchard SC. Quantifying secondary transport at single-molecule resolution. Nature 575:528–534, 2019. doi: 10.1038/s41586-019-1747-5

Elshenawy MM, Canty JT, Oster L, Ferro LS, Zhou Z, Blanchard SC, Yildiz A. Cargo adaptors regulate stepping and force generation of mammalian dynein-dynactin. Nat Chem Biol 15:1093–1101, 2019. doi: 10.1038/s41589-019-0352-0

McMahon M, Contreras A, Holm M, Uechi T, Forester CM, Pang X, Jackson C, Calvert ME, Chen B, Quigley DA, Luk JM, Kelley RK, Gordan JD, Gill RM, Blanchard SC*, Ruggero D*. A single H/ACA small nucleolar RNA mediates tumor suppression downstream of oncogenic RAS. eLife 2019. doi: 10.7554/eLife.48847. *Co-Corresponding Authors

LeVine MV, Terry DS, Khelashvili G, Siegel ZS, Quick M, Javitch JA, Blanchard SC, Weinstein H. The allosteric mechanism of substrate-specific transport in SLC6 is mediated by a volumetric sensor. Proc Natl Acad Sci USA 116:15947–15956, 2019. doi: 10.1073/pnas.1903020116

Gutzeit VA, Thibado J, Stor DS, Zhou Z, Blanchard SC, Andersen OS, Levitz J. Conformational dynamics between transmembrane domains and allosteric modulation of a metabotropic glutamate receptor. eLife 2019 doi: 10.7554/eLife.45116

Prakash V, Carson BB, Feenstra JM, Dass RA, Sekyrova P, Hoshino A, Petersen J, Guo Y, Parks MM, Kurylo CM, Batchelder JE, Haller K, Hashimoto A, Rundqivst H, Condeelis JS, Allis CD, Drygin D, Nieto MA, Andäng M, Percipalle P, Bergh J, Adameyko I, Farrants A-KÖ, Hartman J, Lyden D, Pietras K, Blanchard SC, Vincent CT. Ribosome biogenesis during cell cycle arrest fuels EMT in development and disease. Nat Commun 10:2110, 2019. doi: 10.1038/s41467-019-10100-8

Lu M, Ma X, Castillo-Menendez LR, Gorman J, Alsahafi N, Ermel U, Terry DS, Chambers M, Peng D, Zhang B, Zhou T, Reichard N, Wang K, Grover JR, Carman BP, Gardner MR, Nikić-Spiegel I, Sugawara A, Arthos J, Lemke EA, Smith AB 3rd, Farzan M, Abrams C, Munro JB, McDermott AB, Finzi A, Kwong PD, Blanchard SC, Sodroski JG, Mothes W. Associating HIV-1 envelope glycoprotein structures with states on the virus observed by smFRET. Nature Apr;568(7752):415-419, 2019. doi:10.1038/s41586-019-1101-y. Epub 2019 Apr 10. PubMed PMID: 30971821; PubMed Central PMCID: PMC6655592

Pellegrino S, Meyer M, Könst ZA, Holm M, Voora VK, Kashinskaya D, Zanette C, Mobley DL, Yusupova G, Vanderwal CD, Blanchard SC, Yusupov M. Understanding the role of intermolecular interactions between lissoclimides and the eukaryotic ribosome. Nucleic Acids Res Apr 8;47(6):3223-3232, 2019. doi: 10.1093/nar/gkz053. PubMed PMID: 30759226; PubMed Central PMCID: PMC6451132

Parks MM, Kurylo CM, Batchelder JE, Theresa Vincent C, Blanchard SC. Implications of sequence variation on the evolution of rRNA. Chromosome Res Mar;27(1-2):89-93, 2019. doi: 10.1007/s10577-018-09602-w. Epub 2019 Feb 5. Review. PubMed PMID: 30719681; PubMed Central PMCID: PMC6505490.

Flis J, Holm M, Rundlet EJ, Loerke J, Hilal T, Dabrowski M, Bürger J, Mielke T, Blanchard SC, Spahn CMT, Budkevich TV. tRNA Translocation by the Eukaryotic 80S Ribosome and the Impact of GTP Hydrolysis. Cell Rep Dec 4;25(10):2676-2688.e7, 2018. doi: 10.1016/j.celrep.2018.11.040. PubMed PMID: 30517857;  PubMed Central PMCID: PMC6314685

Kurylo CM, Parks MM, Juette MF, Zinshteyn B, Altman RB, Thibado JK, Vincent CT, Blanchard SC. Endogenous rRNA Sequence Variation Can Regulate Stress Response Gene Expression and Phenotype. Cell Rep Oct 2;25(1):236-248.e6, 2018. doi: 10.1016/j.celrep.2018.08.093. PubMed PMID: 30282032; PubMed Central PMCID: PMC6312700

Blanchard SC. A Much-Needed Boost for the Dwindling Antibiotic Pipeline. Mol Cell Apr 5;70(1):3-5, 2018. doi: 10.1016/j.molcel.2018.03.023. PubMed PMID:29625037; PubMed Central PMCID: PMC6296369

Terry DS, Kolster RA, Quick M, LeVine MV, Khelashvili G, Zhou Z, Weinstein H, Javitch JA, Blanchard SC. A partially-open inward-facing intermediate conformation of LeuT is associated with Na(+) release and substrate transport. Nat Commun Jan 15;9(1):230, 2018. doi: 10.1038/s41467-017-02202-y. PubMed PMID:29335402; PubMed Central PMCID: PMC5768729

Parks MM, Kurylo CM, Dass RA, Bojmar L, Lyden D, Vincent CT, Blanchard SC. Variant ribosomal RNA alleles are conserved and exhibit tissue-specific expression. Sci Adv Feb 28;4(2):eaao0665, 2018. doi: 10.1126/sciadv.aao0665. eCollection 2018 Feb. PubMed PMID: 29503865; PubMed Central PMCID: PMC5829973

Ma X, Lu M, Gorman J, Terry DS, Hong X, Zhou Z, Zhao H, Altman RB, Arthos J, Blanchard SC, Kwong PD, Munro JB, Mothes W. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations. Elife Mar 21;7, 2018. pii: e34271. doi: 10.7554/eLife.34271. [Epub ahead of print] PubMed PMID: 29561264

Dyla M, Terry DS, Kjaergaard M, Andersen JL, Knudsen CR, Altman RB, Nissen P, Blanchard SC. Dynamics of P-type ATPase transport cycle revealed by single molecule FRET Nature 2017. doi:10.1038/nature24296

Alejo JL, Blanchard SC. Miscoding-Induced stalling of substrate translocation on the bacterial ribosome. Proc Natl Adad Sci USA 114(41):E8606-E8610, 2017. PMID:28973849

Gregorio GG, Masureel M, Hilger D, Terry DS, Juette MF, Zhao H, Zhou Z, Perez-Aguilar JM, Hauge M, Mathiasen S, Javitch JA, Weinstein H, Kobilka BK, Blanchard SC. Single-molecule analysis of ligand efficacy in beta2AR-G protein activation. Nature 547(7661), 2017. PMID:28607487

Vušurović N, Altman RB, Micura R, Blanchard SC. Pseudoknot formation seeds the twister ribozyme cleavage reaction coordinate. J Amer Chem Soc 139(24):8196-8193, 2017. PMID: 28598157

Zheng Q, Jockusch S, Zhou Z, Altman RB, Zhao H, Asher W, Holsey M, Mathiasen, S, Geggier P, Javitch JA, Blanchard SC. Electronic tuning of self-healing fluorophores for live-cell and single-molecule imaging. Chem Sci 8(1):755-762, 2017. PMID: 28377799; PMCID: PMC5299821

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Herschhorn A, Ma X, Gu C, Ventura JD, Castillo-Menendez L, Melillo B, Terry DS, Smith AB 3rd, Blanchard SC, Munro JB, Mothes W, Finzi A, Sodroski Release of gp120 restraints leads to an entry-competent intermediate state of HIV-1 envelope glycoproteins. J MBio 7(5):e01598-16, 2016. PMID: 27795397

Dyla M, Andersen JL, Kjaergaard M, Birkedal V, Terry DS, Altman RB, Blanchard SC, Nissen P, Knudsen CR. Engineering a prototypic P-type ATPase Listeria Monocytogenes Ca2+-ATPase 1 for single-molecule FRET studies. Bioconjug Chem 27(9):2176-2187, 2016. PMID: 27501274

Dass RA, Sarshad AA, Carson BB, Feenstra JM, Kaur A, Obrdlik A, Parks MM, Prakash V, Love DK, Pietras K, Serra R, Blanchard SC, Percipalle P, Brown AM, Vincent CT. Wnt5a signals through Dvl1 to repress ribosomal DNA transcription by RNA polymerase I. Plos Genet 12(8):e1006217, 2016. PMID: 27500936

Cocozaki AI, Altman RB, Huang J, Buurman ET, Kazmirski SL, Doig P, Prince DB, Blanchard SC, Cate JH, Ferguson AD. Resistance mutations generate divergent antibiotic susceptibility profiles against translation inhibitors. Proc Natl Adad Sci USA 113(29):8188-8193, 2016. PMID: 27382179

Arenz S, Juette MF, Graf M, Nguyen F, Huter P, Polikanov YS Blanchard SC, Wilson DN. Structures of the orthosomycin antibiotics avilamycin and everninimicin in complex with the bacterial 70S ribosome. Proc Natl Adad Sci USA 113(27):7527-7532, 2016. PMID 27330110

Juette MF, Terry DS, Wasserman MR, Altman RB, Zhou Z, Zhao H, Blanchard SC. Single-molecule imaging of non-equilibrium molecular ensembles on the millisecond time scale. Nature Methods 13(4):341-344, 2016. PMID: 26878382

Wasserman MR.*, Alejo JL.*, Altman RB, Blanchard SC. Multiperspective smFRET reveals rate-determining late intermediates of ribosomal translocation Nature Structural & Molecular Biology 23(4):333-341, 2016. PMID:27174988

Zheng Q, Jockusch S, Rodriguez-Calero GG, Zhou Z, Zhao H, Altman RB, Abruna HD, Blanchard SC. Intra-molecular triplet energy transfer is a general approach to improve organic fluorophore photostability. Photochem Photobiol Sci 15(2):196-203, 2015. PMID:26700693

Ferguson A, Wang L, Altman RB, Terry DS, Juette MF, Burnett BJ, Alejo JL, Dass RA, Blanchard SC. Functional dynamics of the human ribosome. Mol Cell 5(60):475-486, 2015.

Ummat A, Sebra R, Pang A, Pendleton M, Franzen O, Rausch T, Stutz AM, Stedman W, Anantharman T, Hastie A, Dai H, Fritz MHY, Cao H, Cohain A, Deicus G, Durrett RE, Blanchard SC, Altman RA, Chin CS, Guo Y, Paxinos E, Korbel JO, Darnell RB, McCombie WR, Kwok PY, Mason CE, Schadt EE, Bashir A. Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nature Methods 12(8):780-786, 2015.

Do Kwon Y, Pancera M, Acharya P, Georgiev IS, Crooks ET, Gorman J, Joyce MG,Guttman M, Ma X, Narpala S, Soto C, Terry DS, Yang Y, Zhou T, Ahlsen G, Bailer RT, Chambers M, Chuang GY, Doria-Rose NA, Druz A, Hallen MA, Harned A, Kirys T,Louder MK, O'Dell S, Ofek G, Osawa K, Prabhakaran M, Sastry M, Stewart-Jones GB, Stuckey J, Thomas PV, Tittley T, Williams C, Zhang B, Zhao H, Zhou Z, Donald BR, Lee LK, Zolla-Pazner S, Baxa U, Schön A, Freire E, Shapiro L, Lee KK, Arthos J, Munro JB, Blanchard SC, Mothes W, Binley JM, McDermott AB, Mascola JR, Kwong PD. Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. Nat Struct Mol Biol 22(7):522-531, 2015. PMID: 26098315

Wasserman MR, Pulk A, Zhou Z, Altman RB, Zinder JC, Green KD, Garneau-Tsodikova S, Cate JHD, Blanchard SC. Chemically related 4,5-linked aminoglycoside antibiotics drive subunit rotation in opposite directions. Nat Communications 6(7896), 2015.

Noeske J, Wasserman MR, Terry DS, Altman RB, Blanchard SC, Cate JHD. High-resolution structure of the Esherechia coli ribosome. Nature Struct Mol Biol 22(4):336-341, 2015.

Polikanov YS, Starosta AL, Juette MF, Altman RB, Terry DS, Lu W, Burnett BJ, Dinos G, Reynolds K, Blanchard SC*, Steitz TA*, Wilson DN*. Distinct tRNA accommodation intermediates observed on the ribosome with the antibiotics hygromycin A and A201A. Mol Cell 58(5):832-844, 2015. PMID: 26028538; PMCID: PMC4458074 *Co-Corresponding Authors

Lv Z, Krasnoslobodtsev AV, Zhang Y, Ysselstein D, Rochet J-C, Blanchard SC, Lyubchenko YL. Direct detection of alpha-synuclein dimerization dynamics. Biophys J 108(8):2038-2047, 2015. PMID:25902443

Akyuz N, Georgieva ER, Zhou Z, Stolzenberg S, Cuendet MA, Khelashvili G, Altman RB, Terry DS, Freed JH, Weinstein H, Boudker O*, Blanchard SC*. Transport domain unlocking sets the uptake rate of an aspartate transporter Nature 518(7537):68-73, 2015. *Co-Corresponding Authors

Olivier NB, Altman RB, Noeske J, Basarab GS, Code E, Ferguson AD, Gao N, Huang J, Juette MF, Livchak S, Miller MD, Prince BD, Cate JHD, Buurman ET*, Blanchard SC*. Negamycin induces translational stalling and miscoding by binding to the small subunit head domain of the Escherichia Coli ribosome. Proc Natl Acad Sci USA 111(46):16274-16279, 2014. *Co-Corresponding Authors (Highlighted in Faculty of 1000)

Munro JB, Gorman J, Stuckey J, Kwong P, Blanchard SC*, Mothes W*. Conformational dynamics of singe HIV-1 envelope trimers on the surface of native virions. Science 346(6210):759-763, 2014. *Co-Corresponding Authors

Pancera M, Zhou T, Druz A, Georgiev IS, Soto C, Gorman J, Huang J, Acharya P, Chuang GY, Ofek G, Stewart-Jones GB, Stuckey J, Bailer RT, Joyce MG, Louder MK, Tumba N, Yang Y, Zhang B, Cohen MS, Haynes BF, Mascola JR, Morris L, Munro JB, Blanchard SC, Mothes W, Connors M, Kwong PD. Structure and immune recognition of trimeric pre-fusion HIV-1 Env. Nature 514(7523):455-61, 2014.

Burnett BJ, Altman RB, Ferguson AN, Wasserman MR, Zhou Z, Blanchard SC. Direct Evidence of an Elongation Factor Tu/Ts (GTP)aa-tRNA quaternary Complex J Biol Chem Aug 22;289(34):23917-27, 2014. PubMed PMID:24990941

Zheng Q, Jockusch S, Zhou Z, Blanchard SC. The contribution of reactive oxygen species to the photobleaching of organic fluorophores. Photochem Photobiol 90(2):448-54, 2014. PMID:24188468; PMCID: PMC3959289.

Zheng Q, Juette MF, Jockusch S, Wasserman MR, Zhou Z, Altman RB, Blanchard SC. Ultra-stable organic fluorophores for single-molecule research. Chem Soc Rev Feb 21;43(4):1044-56, 2014. doi: 10.1039/c3cs60237k. Review. PubMed PMID:24177677; PubMed Central PMCID: PMC3946787

Last update: November 2023