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Powers, Evan
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Powers, Evan

Institute Investigator
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Positions

  • 2017 - Institute Investigator, Chemistry , Scripps Research
  • 2008 - 2017 Associate Professor of Chemistry, Chemistry , Scripps Research
  • 2000 - 2008 Assistant Professor, Chemistry , Scripps Research
  • 1999 - 2000 Research Associate, Chemistry , Scripps Research
Dr. Evan Powers is interested in the energetics and mechanisms of protein folding and aggregation.

Research Areas research areas

  • Alzheimer (UMLS)

Contact

  • epowers@scripps.edu

Websites

  • Evan Powers, Ph.D.
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Publications

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    • Grandjean, J. M. D., Madhavan, A., Cech, L., Seguinot, B. O., Paxman, R. J., Smith, E., Scampavia, L., Powers, E. T., Cooley, C. B., Plate, L., Spicer, T. P., Kelly, J. W., et al. Pharmacologic IRE1/XBP1s activation confers targeted ER proteostasis reprogramming Nature Chemical Biology  2020  DOI:10.1038/s41589-020-0584-z  PMID:32690944
    • Nelson, L. T., Paxman, R. J., Xu, J., Webb, B., Powers, E. T., Kelly, J. W. Blinded potency comparison of transthyretin kinetic stabilisers by subunit exchange in human plasma Amyloid-Journal of Protein Folding Disorders  2020  DOI:10.1080/13506129.2020.1808783  PMID:32811187
    • Pobre, K. F. R., Powers, D. L., Ghosh, K., Gierasch, L. M., Powers, E. T. Kinetic versus thermodynamic control of mutational effects on protein homeostasis: A perspective from computational modeling and experiment Protein Science  2019 28:1324-1339  DOI:10.1002/pro.3639  PMID:31074892  PMCID:PMC6566562
    • Monteiro, C., Mesgazardeh, J. S., Anselmo, J., Fernandes, J., Novais, M., Rodrigues, C., Brighty, G. J., Powers, D. L., Powers, E. T., Coelho, T., Kelly, J. W. Predictive model of response to tafamidis in hereditary ATTR polyneuropathy JCI Insight  2019 4  DOI:10.1172/jci.insight.126526  PMID:31217346
    • Grandjean, J. M. D., Plate, L., Morimoto, R. I., Bollong, M. J., Powers, E. T., Wiseman, R. L. Deconvoluting stress-responsive proteostasis signaling pathways for pharmacologic activation using targeted RNA sequencing ACS Chemical Biology  2019 14:784-795  DOI:10.1021/acschembio.9b00134  PMID:30821953  PMCID:PMC6474822
    • Lampkin, B. J., Monteiro, C., Powers, E. T., Bouc, P. M., Kelly, J. W., VanVeller, B. A designed protein binding-pocket to control excited-state intramolecular proton transfer fluorescence Organic & Biomolecular Chemistry  2019 17:1076-1080  DOI:10.1039/c8ob02673d  PMID:30534794
    • Paxman, R., Plate, L., Blackwood, E. A., Glembotski, C., Powers, E. T., Wiseman, R. L., Kelly, J. W. Pharmacologic ATF6 activating compounds are metabolically activated to selectively modify endoplasmic reticulum proteins Elife  2018 7  DOI:10.7554/eLife.37168  PMID:30084354  PMCID:PMC6080950
    • Kroeger, H., Grimsey, N., Paxman, R., Chiang, W. C., Plate, L., Jones, Y., Shaw, P. X., Trejo, J., Tsang, S. H., Powers, E., Kelly, J. W., Wiseman, R. L., et al. The unfolded protein response regulator ATF6 promotes mesodermal differentiation Science Signaling  2018 11  DOI:10.1126/scisignal.aan5785  PMID:29440509
    • Morgan, G. J., Burkhardt, D. H., Kelly, J. W., Powers, E. T. Translation efficiency is maintained at elevated temperature in Escherichia coli Journal of Biological Chemistry  2018 293:777-793  DOI:10.1074/jbc.RA117.000284  PMID:29183994  PMCID:PMC5777253
    • Mortenson, D. E., Brighty, G. J., Plate, L., Bare, G., Chen, W., Li, S. H., Wang, H., Cravatt, B. F., Forli, S., Powers, E. T., Sharpless, K. B., Wilson, I. A., et al. "Inverse drug discovery" strategy to identify proteins that are targeted by latent electrophiles as exemplified by aryl fluorosulfates Journal of the American Chemical Society  2018 140:200-210  DOI:10.1021/jacs.7b08366
    • Schonhoft, J. D., Monteiro, C., Plate, L., Eisele, Y. S., Kelly, J. M., Boland, D., Parker, C. G., Cravatt, B. F., Teruya, S., Helmke, S., Maurer, M., Berk, J., et al. Peptide probes detect misfolded transthyretin oligomers in plasma of hereditary amyloidosis patients Science Translational Medicine  2017 9  DOI:10.1126/scitranslmed.aam7621  PMID:28904227
    • Connelly, S., Mortenson, D. E., Choi, S., Wilson, I. A., Powers, E. T., Kelly, J. W., Johnson, S. M. Semi-quantitative models for identifying potent and selective transthyretin amyloidogenesis inhibitors Bioorganic & Medicinal Chemistry Letters  2017 27:3441-3449  DOI:10.1016/j.bmcl.2017.05.080  PMID:28625364
    • Chen, K. C., Qu, S., Chowdhury, S., Noxon, I. C., Schonhoft, J. D., Plate, L., Powers, E. T., Kelly, J. W., Lander, G. C., Wiseman, R. L. The endoplasmic reticulum HSP40 co-chaperone ERdj3/DNAJB11 assembles and functions as a tetramer EMBO Journal  2017 36:2296-2309  DOI:10.15252/embj.201695616
    • Ardejani, M. S., Powers, E. T., Kelly, J. W. Using cooperatively folded peptides to measure interaction energies and conformational propensities Accounts of Chemical Research  2017 50:1875-1882  DOI:10.1021/acs.accounts.7b00195  PMID:28723063  PMCID:PMC5584629
    • Hingorani, K. S., Metcalf, M. C., Deming, D. T., Garman, S. C., Powers, E. T., Gierasch, L. M. Ligand-promoted protein folding by biased kinetic partitioning Nature Chemical Biology  2017 13:369-371  PMID:28218913  PMCID:PMC5362304
    • Plate, L., Cooley, C. B., Chen, J. J., Paxman, R. J., Gallagher, C. M., Madoux, F., Genereux, J. C., Dobbs, W., Garza, D., Spicer, T. P., Scampavia, L., Brown, S. J., et al. Small molecule proteostasis regulators that reprogram the ER to reduce extracellular protein aggregation Elife  2016 5  DOI:10.7554/eLife.15550  PMID:27435961  PMCID:PMC4954754
    • Chen, W., Kong, L., Connelly, S., Liu, Y., Wilson, I. A., Powers, E. T., Kelly, J. W. Stabilizing the C(H)2 domain of an antibody by engineering in an enhanced aromatic sequon ACS Chemical Biology  2016 11:1852-1861  DOI:10.1021/acschembio.5b01035  PMID:27128252  PMCID:PMC4852379
    • Hsu, C. H., Park, S., Mortenson, D. E., Foley, B. L., Wang, X., Woods, R. J., Case, D. A., Powers, E. T., Wong, C. H., Dyson, H. J., Kelly, J. W. The dependence of carbohydrate-aromatic interaction strengths on the structure of the carbohydrate Journal of the American Chemical Society  2016 138:7636-7648  DOI:10.1021/jacs.6b02879  PMID:27249581  PMCID:PMC4924591
    • Chen, W., Dong, J., Plate, L., Mortenson, D. E., Brighty, G. J., Li, S., Liu, Y., Galmozzi, A., Lee, P. S., Hulce, J. J., Cravatt, B. F., Saez, E., et al. Arylfluorosulfates inactivate intracellular lipid binding protein(s) through chemoselective SuFEx reaction with a binding site Tyr residue Journal of the American Chemical Society  2016 138:7353-7364  DOI:10.1021/jacs.6b02960  PMID:27191344  PMCID:PMC4909538
    • Eisele, Y. S., Monteiro, C., Fearns, C., Encalada, S. E., Wiseman, R. L., Powers, E. T., Kelly, J. W. Targeting protein aggregation for the treatment of degenerative diseases Nature Reviews Drug Discovery  2015 14:759-780  DOI:10.1038/nrd4593  PMID:26338154  PMCID:PMC4628595
    • Murray, A. N., Chen, W., Antonopoulos, A., Wiseman, R. L., Dell, A., Haslam, S. M., Powers, D. L., Powers, E. T., Kelly, J. W. Enhanced aromatic sequons increase oligosaccharyltransferase glycosylation efficiency and glycan homogeneity Chemistry & Biology  2015 22:1052-1062  DOI:10.1016/j.chembiol.2015.06.017  PMID:26190824  PMCID:PMC4546532
    • Powers, E. T. Translation: An O-GlcNAc stamp of approval Nature Chemical Biology  2015 11:307-308  DOI:10.1038/nchembio.1777  PMID:25774940
    • Cho, Y., Zhang, X., Pobre, K. F. R., Liu, Y., Powers, D. L., Kelly, J. W., Gierasch, L. M., Powers, E. T. Individual and collective contributions of chaperoning and degradation to protein homeostasis in E. coli Cell Reports  2015 11:321-333  DOI:10.1016/j.celrep.2015.03.018  PMID:25843722  PMCID:PMC4401642
    • Hebert, D. N., Lamriben, L., Powers, E. T., Kelly, J. W. The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis Nature Chemical Biology  2014 10:902-910  PMID:25325701  PMCID:PMC4232232
    • Ryno, L. M., Genereux, J. C., Naito, T., Morimoto, R. I., Powers, E. T., Shoulders, M. D., Wiseman, R. L. Characterizing the altered cellular proteome induced by the stress-independent activation of heat shock factor 1 ACS Chemical Biology  2014 9:1273-1283  DOI:10.1021/cb500062n  PMID:24689980  PMCID:PMC4076015
    • Baranczak, A., Connelly, S., Liu, Y., Choi, S., Grimster, N. P., Powers, E. T., Wilson, I. A., Kelly, J. W. Fluorogenic small molecules requiring reaction with a specific protein to create a fluorescent conjugate for biological imaging: what we know and what we need to learn Biopolymers  2014 101:484-495  DOI:10.1002/bip.22407  PMID:24105107  PMCID:PMC4128284
    • Rappley, I., Monteiro, C., Novais, M., Baranczak, A., Solis, G., Wiseman, R. L., Helmke, S., Maurer, M. S., Coelho, T., Powers, E. T., Kelly, J. W. Quantification of transthyretin kinetic stability in human plasma using subunit exchange Biochemistry  2014 53:1993-2006  DOI:10.1021/bi500171j  PMID:24661308  PMCID:PMC3977577
    • Chen, W., Enck, S., Price, J. L., Powers, D. L., Powers, E. T., Wong, C. H., Dyson, H. J., Kelly, J. W. Structural and energetic basis of carbohydrate-aromatic packing interactions in proteins Journal of the American Chemical Society  2013 135:9877-9884  DOI:10.1021/ja4040472  PMID:23742246  PMCID:PMC3715148
    • Talantova, M., Sanz-Blasco, S., Zhang, X. F., Xia, P., Akhtar, M. W., Okamoto, S., Dziewczapolski, G., Nakamura, T., Cao, G., Pratt, A. E., Kang, Y. J., Tu, S., et al. Aβ induces astrocytic glutamate release, extrasynaptic NMDA receptor activation, and synaptic loss Proceedings of the National Academy of Sciences of the United States of America  2013 110:E2518-E2527  DOI:10.1073/pnas.1306832110  PMID:23776240  PMCID:PMC3704025
    • Penchala, S. C., Connelly, S., Wang, Y., Park, M. S., Zhao, L., Baranczak, A., Rappley, I., Vogel, H., Liedtke, M., Witteles, R. M., Powers, E. T., Reixach, N., et al. AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin Proceedings of the National Academy of Sciences of the United States of America  2013 110:9992-9997  DOI:10.1073/pnas.1300761110  PMID:23716704  PMCID:PMC3683741
    • Grimster, N. P., Connelly, S., Baranczak, A., Dong, J. J., Krasnova, L. B., Sharpless, K. B., Powers, E. T., Wilson, I. A., Kelly, J. W. Aromatic sulfonyl fluorides covalently kinetically stabilize transthyretin to prevent amyloidogenesis while affording a fluorescent conjugate Journal of the American Chemical Society  2013 135:5656-5668  DOI:10.1021/ja311729d  PMID:23350654  PMCID:PMC3630275
    • Powers, E. T., Balch, W. E. Diversity in the origins of proteostasis networks: a driver for protein function in evolution Nature Reviews Molecular Cell Biology  2013 14:237-248  DOI:10.1038/nrm3542  PMID:23463216  PMCID:PMC3718298
    • Johnson, S. M., Connelly, S., Fearns, C., Powers, E. T., Kelly, J. W. The transthyretin amyloidoses: from delineating the molecular mechanism of aggregation linked to pathology to a regulatory-agency-approved drug Journal of Molecular Biology  2012 421:185-203  DOI:10.1016/j.jmb.2011.12.060  PMID:22244854  PMCID:PMC3350832
    • Bulawa, C. E., Connelly, S., Devit, M., Wang, L., Weigel, C., Fleming, J. A., Packman, J., Powers, E. T., Wiseman, R. L., Foss, T. R., Wilson, I. A., Kelly, J. W., et al. Tafamidis, a potent and selective transthyretin kinetic stabilizer that inhibits the amyloid cascade Proceedings of the National Academy of Sciences of the United States of America  2012 109:9629-9634  DOI:10.1073/pnas.1121005109  PMID:22645360  PMCID:PMC3386102
    • Powers, E. T., Powers, D. L., Gierasch, L. M. FoldEco: A model for proteostasis in E. coli Cell Reports  2012 1:265-276  DOI:10.1016/j.celrep.2012.02.011  PMID:22509487  PMCID:PMC3324317
    • Price, J. L., Culyba, E. K., Chen, W., Murray, A. N., Hanson, S. R., Wong, C. H., Powers, E. T., Kelly, J. W. N-glycosylation of enhanced aromatic sequons to increase glycoprotein stability Biopolymers  2012 98:195-211  DOI:10.1002/bip.22030  PMID:22782562  PMCID:PMC3539202
    • Orwig, S. D., Tan, Y. L., Grimster, N. P., Yu, Z. Q., Powers, E. T., Kelly, J. W., Lieberman, R. L. Binding of 3,4,5,6-tetrahydroxyazepanes to the acid-β-glucosidase active site: implications for pharmacological chaperone design for Gaucher disease Biochemistry  2011 50:10647-10657  DOI:10.1021/bi201619z  PMID:22047104  PMCID:PMC3235649
    • Price, J. L., Powers, E. T., Kelly, J. W. N-PEGylation of a reverse turn is stabilizing in multiple sequence contexts, unlike N-GlcNAcylation ACS Chemical Biology  2011 6:1188-1192  DOI:10.1021/cb200277u  PMID:21939258  PMCID:PMC3220771
    • Lee, J., Culyba, E. K., Powers, E. T., Kelly, J. W. Amyloid-beta forms fibrils by nucleated conformational conversion of oligomers Nature Chemical Biology  2011 7:602-609  DOI:10.1038/nchembio.624  PMID:21804535  PMCID:PMC3158298
    • Alhamadsheh, M. M., Connelly, S., Cho, A., Reixach, N., Powers, E. T., Pan, D. W., Wilson, I. A., Kelly, J. W., Graef, I. A. Potent kinetic stabilizers that prevent transthyretin-mediated cardiomyocyte proteotoxicity Science Translational Medicine  2011 3:97ra81  DOI:10.1126/scitranslmed.3002473  PMID:21865539  PMCID:PMC3227540
    • Price, J. L., Powers, D. L., Powers, E. T., Kelly, J. W. Glycosylation of the enhanced aromatic sequon is similarly stabilizing in three distinct reverse turn contexts Proceedings of the National Academy of Sciences of the United States of America  2011 108:14127-14132  DOI:10.1073/pnas.1105880108  PMID:21825145  PMCID:PMC3161607
    • Groenning, M., Campos, R. I., Fagerberg, C., Rasmussen, A. A., Eriksen, U. H., Powers, E. T., Hammarstrom, P. Thermodynamic stability and denaturation kinetics of a benign natural transthyretin mutant identified in a danish kindred Amyloid-Journal of Protein Folding Disorders  2011 18:35-46  DOI:10.3109/13506129.2011.560215  PMID:21406045
    • Solomon, J. P., Bourgault, S., Powers, E. T., Kelly, J. W. Heparin binds 8 kDa gelsolin cross-β-sheet oligomers and accelerates amyloidogenesis by hastening fibril extension Biochemistry  2011 50:2486-2498  DOI:10.1021/bi101905n  PMID:21348501  PMCID:PMC3068913
    • Powers, E. T., Balch, W. E. Protein folding: Protection from the outside Nature  2011 471:42-43  DOI:10.1038/471042a  PMID:21368816
    • Culyba, E. K., Price, J. L., Hanson, S. R., Dhar, A., Wong, C. H., Gruebele, M., Powers, E. T., Kelly, J. W. Protein native-state stabilization by placing aromatic side chains in N-glycosylated reverse turns Science  2011 331:571-575  DOI:10.1126/science.1198461  PMID:21292975  PMCID:PMC3099596
    • Price, J. L., Shental-Bechor, D., Dhar, A., Turner, M. J., Powers, E. T., Gruebele, M., Levy, Y., Kelly, J. W. Context-dependent effects of asparagine glycosylation on Pin WW folding kinetics and thermodynamics Journal of the American Chemical Society  2010 132:15359-15367  DOI:10.1021/ja106896t  PMID:20936810  PMCID:PMC2965790
    • Solomon, J. P., Yonemoto, I. T., Murray, A. N., Price, J. L., Powers, E. T., Balch, W. E., Kelly, J. W. The 8 and 5 kDa fragments of plasma gelsolin form amyloid fibrils by a nucleated polymerization mechanism, while the 68 kDa fragment is not amyloidogenic Biochemistry  2009 48:11370-11380  DOI:10.1021/bi901368e  PMID:19904968  PMCID:PMC2907741
    • Usui, K., Hulleman, J. D., Paulsson, J. F., Siegel, S. J., Powers, E. T., Kelly, J. W. Site-specific modification of Alzheimer's peptides by cholesterol oxidation products enhances aggregation energetics and neurotoxicity Proceedings of the National Academy of Sciences of the United States of America  2009 106:18563-18568  DOI:10.1073/pnas.0804758106  PMID:19841277  PMCID:PMC2774025
    • Hutt, D. M., Powers, E. T., Balch, W. E. The proteostasis boundary in misfolding diseases of membrane traffic FEBS Letters  2009 583:2639-2646  DOI:10.1016/j.febslet.2009.07.014  PMID:19708088  PMCID:PMC2805282
    • Fuller, A. A., Du, D., Liu, F., Davoren, J. E., Bhabha, G., Kroon, G., Case, D. A., Dyson, H. J., Powers, E. T., Wipf, P., Gruebele, M., Kelly, J. W. Evaluating beta-turn mimics as beta-sheet folding nucleators Proceedings of the National Academy of Sciences of the United States of America  2009 106:11067-11072  DOI:10.1073/pnas.0813012106  PMID:19541614  PMCID:PMC2708776
    • Gao, J. M., Bosco, D. A., Powers, E. T., Kelly, J. W. Localized thermodynamic coupling between hydrogen bonding and microenvironment polarity substantially stabilizes proteins Nature Structural & Molecular Biology  2009 16:684-690  DOI:10.1038/nsmb.1610  PMID:19525973  PMCID:PMC2754385
    • Hanson, S. R., Culyba, E. K., Hsu, T. L., Wong, C. H., Kelly, J. W., Powers, E. T. The core trisaccharide of an N-linked glycoprotein intrinsically accelerates folding and enhances stability Proceedings of the National Academy of Sciences of the United States of America  2009 106:3131-3136  DOI:10.1073/pnas.0810318105  PMID:19204290  PMCID:PMC2651298
    • Powers, E. T., Morimoto, R. I., Dillin, A., Kelly, J. W., Balch, W. E. Biological and chemical approaches to diseases of proteostasis deficiency Annual Review of Biochemistry  2009 78:959-991  DOI:10.1146/annurev.biochem.052308.114844  PMID:19298183
    • Powers, E. T., Balch, W. E. Costly mistakes: translational infidelity and protein homeostasis Cell  2008 134:204-206  DOI:10.1016/j.cell.2008.07.005  PMID:18662533
    • Babbes, A. R. H., Powers, E. T., Kelly, J. W. Quantification of the thermodynamically linked quaternary and tertiary structural stabilities of transthyretin and its disease-associated variants: the relationship between stability and amyloidosis Biochemistry  2008 47:6969-6984  DOI:10.1021/bi800636q  PMID:18537267  PMCID:PMC2667099
    • Powers, E. T., Powers, D. L. Mechanisms of protein fibril formation: Nucleated polymerization with competing off-pathway aggregation Biophysical Journal  2008 94:379-391  DOI:10.1529/biophysj.107.117168  PMID:17890392  PMCID:PMC2157252
    • Jager, M., Deechongkit, S., Koepf, E. K., Nguyen, H., Gao, J. M., Powers, E. T., Gruebele, M., Kelly, J. W. Understanding the mechanism of beta-sheet folding from a chemical and biological perspective Biopolymers  2008 90:751-758  DOI:10.1002/bip.21101  PMID:18844292
    • Wiseman, R. L., Powers, E. T., Buxbaum, J. N., Kelly, J. W., Balch, W. E. An adaptable standard for protein export from the endoplasmic reticulum Cell  2007 131:809-821  DOI:10.1016/j.cell.2007.10.025  PMID:18022373
    • Wiseman, R. L., Koulov, A., Powers, E., Kelly, J. W., Balch, W. E. Protein energetics in maturation of the early secretory pathway Current Opinion in Cell Biology  2007 19:359-367  DOI:10.1016/j.ceb.2007.05.005  PMID:17686625  PMCID:PMC2094714
    • Siegel, S. J., Bieschke, J., Powers, E. T., Kelly, J. W. The oxidative stress metabolite 4-hydroxynonenal promotes Alzheimer protofibril formation Biochemistry  2007 46:1503-1510  DOI:10.1021/bi061853s  PMID:17279615  PMCID:PMC2530822
    • Bieschke, J., Zhang, Q. H., Bosco, D. A., Lerner, R. A., Powers, E. T., Wentworth, P., Kelly, J. W. Small molecule oxidation products trigger disease-associated protein misfolding Accounts of Chemical Research  2006 39:611-619  DOI:10.1021/ar0500766  PMID:16981677
    • Powers, E. T. The kinetics of nucleated polymerizations at high concentrations: Amyloid fibril formation near and above the "supercritical concentration'' Biophysical Journal  2006 91:122-132  DOI:10.1529/biophysj.105.073767  PMID:16603497  PMCID:PMC1479066
    • Deechongkit, S., Nguyen, H., Jager, M., Powers, E. T., Gruebele, M., Kelly, J. W. Beta-sheet folding mechanisms from perturbation energetics Current Opinion in Structural Biology  2006 16:94-101  DOI:10.1016/j.sbi.2006.01.014  PMID:16442278
    • Bosco, D. A., Fowler, D. M., Zhang, Q. H., Nieva, J., Powers, E. T., Wentworth, P., Lerner, R. A., Kelly, J. W. Elevated levels of oxidized cholesterol metabolites in lewy body disease brains accelerate alpha-synuclein fibrilization Nature Chemical Biology  2006 2:249-253  DOI:10.1038/nchembio782  PMID:16565714
    • Wiseman, R. L., Powers, E. T., Kelly, J. W. Partitioning conformational intermediates between competing refolding and aggregation pathways: Insights into transthyretin amyloid disease Biochemistry  2005 44:16612-16623  DOI:10.1021/bi0511484  PMID:16342952  PMCID:PMC2532856
    • Frankenfield, K. N., Powers, E. T., Kelly, J. W. Influence of the N-terminal domain on the aggregation properties of the prion protein Protein Science  2005 14:2154-2166  DOI:10.1110/ps.051434005  PMID:16046631  PMCID:PMC2279327
    • Deechongkit, S., Powers, E. T., You, S. L., Kelly, J. W. Controlling the morphology of cross beta-sheet assemblies by rational design Journal of the American Chemical Society  2005 127:8562-8570  DOI:10.1021/ja050558c  PMID:15941292
    • Petrassi, H. M., Johnson, S. M., Purkey, H. E., Chiang, K. P., Walkup, T., Jiang, X., Powers, E. T., Kelly, J. W. Potent and selective structure-based dibenzofuran inhibitors of transthyretin amyloidogenesis: Kinetic stabilization of the native state Journal of the American Chemical Society  2005 127:6662-6671  DOI:10.1021/ja044351f  PMID:15869287
    • Bieschke, J., Zhang, Q. H., Powers, E. T., Lerner, R. A., Kelly, J. W. Oxidative metabolites accelerate Alzheimer's amyloidogenesis by a two-step mechanism, eliminating the requirement for nucleation Biochemistry  2005 44:4977-4983  DOI:10.1021/bi0501030  PMID:15794636
    • Razavi, H., Powers, E. T., Purkey, H. E., Adamski-Werner, S. L., Chiang, K. P., Dendle, M. T. A., Kelly, J. W. Design, synthesis, and evaluation of oxazole transthyretin amyloidogenesis inhibitors Bioorganic & Medicinal Chemistry Letters  2005 15:1075-1078  DOI:10.1016/j.bmcl.2004.12.022  PMID:15686915
    • Powers, E. T., Deechongkit, S., Kelly, J. W. Backbone-backbone H-bonds make context-dependent contributions to protein folding kinetics and thermodynamics: lessons from amide-to-ester mutations Advances in Protein Chemistry  2005 72:39-78  DOI:10.1016/s0065-3233(05)72002-7  PMID:16581372
    • Deechongkit, S., Nguyen, H., Powers, E. T., Dawson, P. E., Gruebele, M., Kelly, J. W. Context-dependent contributions of backbone hydrogen bonding to β-sheet folding energetics Nature  2004 430:101-105  DOI:10.1038/nature02611  PMID:15229605
    • Hurshman, A. R., White, J. T., Powers, E. T., Kelly, J. W. Transthyretin aggregation under partially denaturing conditions is a downhill polymerization Biochemistry  2004 43:7365-7381  DOI:10.1021/bi049621l  PMID:15182180
    • Zhang, Q. H., Powers, E. T., Nieva, J., Huff, M. E., Dendle, M. A., Bieschke, J., Glabe, C. G., Eschenmoser, A., Wentworth, P., Lerner, R. A., Kelly, J. W. Metabolite-initiated protein misfolding may trigger Alzheimer's disease Proceedings of the National Academy of Sciences of the United States of America  2004 101:4752-4757  DOI:10.1073/pnas.0400924101  PMID:15034169  PMCID:PMC387320
    • Powers, E. T., Powers, D. L. A perspective on mechanisms of protein tetramer formation Biophysical Journal  2003 85:3587-3599  DOI:10.1016/s0006-3495(03)74777-8  PMID:14645052
    • Lu, J. R., Perumal, S., Powers, E. T., Kelly, J. W., Webster, J. R. P., Penfold, J. Adsorption of beta-hairpin peptides on the surface of water: A neutron reflection study Journal of the American Chemical Society  2003 125:3751-3757  DOI:10.1021/ja0292290  PMID:12656605
    • Colfer, S., Kelly, J. W., Powers, E. T. Factors governing the self-assembly of a beta-hairpin peptide at the air-water interface Langmuir  2003 19:1312-1318  DOI:10.1021/la0207668
    • Hammarstrom, P.*, Wiseman, R. L.*, Powers, E. T., Kelly, J. W. Prevention of transthyretin amyloid disease by changing protein misfolding energetics Science  2003 299:713-716  DOI:10.1126/science.1079589  PMID:12560553 (* = equal contribution)
    • DiDonato, M., Craig, L., Huff, M. E., Thayer, M. M., Cardoso, R. M. F., Kassmann, C. J., Lo, T. P., Bruns, C. K., Powers, E. T., Kelly, J. W., Getzoff, E. D., Tainer, J. A. ALS mutants of human superoxide dismutase form fibrous aggregates via framework destabilization Journal of Molecular Biology  2003 332:601-615  DOI:10.1016/s0022-2836(03)00889-1  PMID:12963370
    • Razavi, H., Palaninathan, S. K., Powers, E. T., Wiseman, R. L., Purkey, H. E., Mohamedmohaideen, N. N., Deechongkit, S., Chiang, K. P., Dendle, M. T. A., Sacchettini, J. C., Kelly, J. W. Benzoxazoles as transthyretin amyloid fibril inhibitors: Synthesis, evaluation, and mechanism of action Angewandte Chemie-International Edition  2003 42:2758-2761  DOI:10.1002/anie.200351179  PMID:12820260
    • Hammarstrom, P., Jiang, X., Hurshman, A. R., Powers, E. T., Kelly, J. W. Sequence-dependent denaturation energetics: A major determinant in amyloid disease diversity Proceedings of the National Academy of Sciences of the United States of America  2002 99:16427-16432  DOI:10.1073/pnas.202495199  PMID:12351683  PMCID:PMC139904
    • Oza, V. B., Smith, C., Raman, P., Koepf, E. K., Lashuel, H. A., Petrassi, H. M., Chiang, K. P., Powers, E. T., Sachettinni, J., Kelly, J. W. Synthesis, structure, and activity of diclofenac analogues as transthyretin amyloid fibril formation inhibitors Journal of Medicinal Chemistry  2002 45:321-332  DOI:10.1021/jm010257n  PMID:11784137
    • Powers, E. T., Yang, S. I., Lieber, C. M., Kelly, J. W. Ordered Langmuir-Blodgett films of amphiphilic beta-hairpin peptides imaged by atomic force microscopy Angewandte Chemie-International Edition  2002 41:127-130  DOI:10.1002/1521-3773(20020104)41:1<127::aid-anie127>3.0.co;2-f  PMID:12491460
    • Kaul, R., Angeles, A. R., Jager, M., Powers, E. T., Kelly, J. W. Incorporating beta-turns and a turn mimetic out of context in loop 1 of the WW domain affords cooperatively folded beta-sheets Journal of the American Chemical Society  2001 123:5206-5212  DOI:10.1021/ja0102890  PMID:11457382
    • Powers, E. T., Kelly, J. W. Medium-dependent self-assembly of an amphiphilic peptide: Direct observation of peptide phase domains at the air-water interface Journal of the American Chemical Society  2001 123:775-776  DOI:10.1021/ja005528i  PMID:11456608
    • Zerkowski, J. A., Powers, E. T., Kemp, D. S. A permutation test for stabilization of polypeptide helices by sequence-dependent side chain interactions: Characterization of a helix initiation site within the myohemerythrin sequence 76-87 Journal of the American Chemical Society  1997 119:1153-1154  DOI:10.1021/ja962642l
    • Rossi, F. M., Powers, E. T., Yoon, R., Rosenberg, L., Meinwald, J. Preparation of 2,3-diamino acids: Stereocontrolled synthesis of an aminated analog of the taxol side chain Tetrahedron  1996 52:10279-10286  DOI:10.1016/0040-4020(96)00562-5
  • chapter

    • Johnson, S. M., Wiseman, R. L., Reixach, N., Paulsson, J. F., Choi, S., Powers, E. T., Buxbaum, J. N., Kelly, J. W. Understanding and ameliorating the TTR amyloidoses Protein Misfolding Diseases. 967-1003. 2010  DOI:10.1002/9780470572702.ch45

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Research

research overview

  • Studies of protein folding and aggregation

    Proteins generally encounter one of two fates after being synthesized. They can fold to their native structure, which enables them to function normally, or they can misfold to a non-native, non-functional structure, which leaves them vulnerable to degradation or aggregation. Protein folding and aggregation are both critically important processes; the former is integral to life, and the latter is strongly associated with devastating diseases, including Alzheimer's and Parkinson's disease. The goal of our research is to improve our understanding of these processes, with an emphasis on energetics and mechanism.
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Background

education and training

  • Ph.D. in Organic Chemistry, Massachusetts Institute of Technology 1999
  • B.A. in Chemistry, Cornell University 1992
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Contact

full name

  • Evan T. Powers

geographic location

  • Scripps California 

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