Collaborative Publications

The Center for Protein Conformational Diseases is composed of a group of highly collaborative investigators whose scientific interests overlap. The breadth and number of collaborative publications amongst members of this group highlight this fact, as well as the trans-departmental and multi-disciplinary approaches used to understand how misfolded proteins lead to human disease. 

2017

Buck TM, Jordahl AS, Yates ME, Preston GM, Cook E, Kleyman TR, Brodsky JL. Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein. Biochem J. 2017 Feb 1; 474(3):357-376. DOI: 10.1042/BCJ20160760.

Kar, K., Baker, M.A., Lengyel, G.A., Hoop, C.L., Kodali, R., Byeon, I.J., Horne, W.S., van der Wel, P.C.A., & Wetzel, R., Backbone engineering within a latent β-hairpin structure to design inhibitors of polyglutamine amyloid formation. J. Mol. Biol. 2017; 429: 308-323

2016

Di Maio, R., PJ Barrett, EK Hoffman, CW Barrett, A Zharikov, A Borah, X Hu, J McCoy, CT Chu, EA Burton, TG Hastings, JT Greenamyre. a-Synuclein binds TOM20 and inhibits mitochondrial protein import in Parkinson’s disease. Sci Transl Med 2016; 8: 342ra78

Manos-Turvey A, Al-Ashtal HA, Needham PG, Hartline CB, Prichard MN, Wipf PBrodsky JL. Dihydropyrimidinones and -thiones with improved activity against human polyomavirus family members. Bioorg Med Chem Lett. 2016;26(20):5087-5091

Sabnis AJ, Guerriero CJ, Olivas V, Sayana A, Shue J, Flanagan J, Asthana S, Paton AW, Paton JC, Gestwicki JE, Walter P, Weissman JS, Wipf P, Brodsky JL, Bivona TG. Combined chemical-genetic approach identifies cytosolic HSP70 dependence in rhabdomyosarcoma. Proc Natl Acad Sci U S A. 2016;113(32):9015-20

Hoop, C.L., Lin, H.-K., Kar, K., Magyarfalvi, G., Lamley, J.M., Boatz, J.C., Mandal, A., Lewandowski, J.R., Wetzel, R., & van der Wel, P.C.A., Huntingtin exon 1 fibrils feature an interdigitated β-hairpin-based polyglutamine core. Proc. Natl. Acad. Sci. USA. 2016; 113: 1546-1551

Sahoo, B., Arduini, I., Drombosky, K.W., Kodali, R., Saunders, L.H., Greenamyre, J.T., & Wetzel, R., Folding landscape of mutant Huntingtin exon1: Diffusible multimers, oligomers and fibrils, and no detectable monomer. PLoS One. 2016; DOI: 10.1371/journal.pone.0155747

Webb TN, Carrisoza-Gaytan R, Montalbetti N, Rued A, Roy A, Socovich AM, Subramanya AR, Satlin LM, Kleyman TR, Carattino MD. Cell-specific regulation of L-WNK1 by dietary K. Am J Physiol Renal Physiol. 2016;310(1):F15-26.

Veit G, Avramescu RG, Chiang AN, Houck SA, Cai Z, Peters KW, Hong JS, Pollard HB, Guggino WB, Balch WE, Skach WR, Cutting GR, Frizzell RA, Sheppard DN, Cyr DM, Sorscher EJ, Brodsky JL, Lukacs GL. From CFTR biology toward combinatorial pharmacotherapy: expanded classification of cystic fibrosis mutations. Mol Biol Cell. 2016;27(3):424-33

2015

Brodsky JL, Frizzell RA. A combination therapy for cystic fibrosis. Cell. 2015;163(1):17

Buck TM, Jordan R, Lyons-Weiler J, Adelman JL, Needham PG, Kleyman TR, Brodsky JL. Expression of three topologically distinct membrane proteins elicits unique stress response pathways in the yeast Saccharomyces cerevisiae. Physiol Genomics. 2015;47(6):198-214

Zharikov A, Cannon JR, Tapias V, Bai Q, Horowitz M, Shah V, El Ayadi A, Hastings TG, Greenamyre JT, Burton EA, shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model, J Clin Invest 2015; 125:2721-35

Wipf P, Eyer BR, Yamaguchi Y, Zhang F, Neal MD, Sodhi CP, Good M, Branca M, Prindle T Jr, Lu P, Brodsky JL, Hackam DJ. Synthesis of anti-inflammatory α-andβ-linked acetamidopyranosides as inhibitors of toll-like receptor 4 (TLR4. Tetrahedron Lett. 2015;56(23):3097-3100

Posimo JM, Weilnau JN, Gleixner AM, Broeren MT, Weiland NL, Brodsky JL, Wipf P, Leak RK. Heat shock protein defenses in the neocortex and allocortex of thetelencephalon. Neurobiol Aging. 2015 May;36(5):1924-37

Crum TS, Gleixner AM, Posimo JM, Mason DM, Broeren MT, Heinemann SD, Wipf PBrodsky JL, Leak RK. Heat shock protein responses to aging and proteotoxicity in the olfactory bulb. J Neurochem. 2015;133(6):780-94

Needham PG, Patel HJ, Chiosis G, Thibodeau PH, Brodsky JL. Mutations in the Yeast Hsp70, Ssa1, at P417 Alter ATP Cycling, Interdomain Coupling, and Specific Chaperone Functions. J Mol Biol. 2015;427(18):2948-65

Cheng MH, Block E, Hu F, Cobanoglu MC, Sorkin A, Bahar I. Insights into the modulation of dopamine transporter function by amphetamine, orphenadrine, and cocaine binding. Front Neurol 2015; 6: 134

Chen J, Ray EC, Yates ME, Buck TM, Brodsky JL, Kinlough CL, Winarski KL, Hughey RP, Kleyman TR, Sheng S. Functional Roles of Clusters of Hydrophobic and Polar Residues in the Epithelial Na+ Channel Knuckle Domain. J Biol Chem. 2015;290(41):25140-50

Prosser DC, Pannunzio AE, Brodsky JL, Thorner J, Wendland B, O'Donnell AF. α-Arrestins participate in cargo selection for both clathrin-independent and clathrin-mediated endocytosis. J Cell Sci. 2015;128(22):4220-34

2014

Kar, K., Arduini, I., Drombosky, K.W., van der Wel, P.C.A., & Wetzel, R., d-polyglutamine amyloid recruits l-polyglutamine monomers and kills cells, J. Mol. Biol. 2014; 426: 816-829

Hoop, C., Lin, H.-K., Kar, K., Hou, Z., Poirier, M., Wetzel, R., & van der Wel, P.C.A., Polyglutamine amyloid core boundaries and flanking domain dynamics in huntingtin fragment fibrils determined by solid-state NMR. Biochem. 2014; 53: 6653-6666

Hecht KA, O'Donnell AF, Brodsky JL. The proteolytic landscape of the yeast vacuole. Cell Logist. 2014;4(1):e28023

LH Sanders, J McCoy, X Hu, PG Mastroberardino, BC Dickinson, CJ Chang, CT Chu, B Van Houten, JT Greenamyre. Mitochondrial DNA damage: molecular marker of vulnerable nigral neurons in Parkinson’s disease. Neurobiol Dis 2014; 70: 214-223

Alvaro CG, O'Donnell AF, Prosser DC, Augustine AA, Goldman A, Brodsky JL, Cyert MS, Wendland B, Thorner J. Specific α-arrestins negatively regulate Saccharomyces cerevisiae pheromone response by down-modulating the G-protein-coupled receptor Ste2. Mol Cell Biol. 2014;34(14):2660-81

Ireland AW, Gobillot TA, Gupta T, Seguin SP, Liang M, Resnick L, Goldberg MT, Manos-Turvey A, Pipas JM, Wipf P, Brodsky JL. Synthesis and structure–activity relationships of small molecule inhibitors of the simian virus 40 T antigen oncoprotein, an anti-polyomaviral target. Bioorg Med Chem. 2014;22(22):6490-502

Adam C, Baeurle A, Brodsky JL, Wipf P, Schrama D, Becker JC, Houben R. The HSP70 modulator MAL3-101 inhibits Merkel cell carcinoma. PLoS One 2014;9(4):e92041

2013

Wang Z, Subramanya AR, Satlin LM, Pastor-Soler NM, Carattino MD, Kleyman TR. Regulation of large-conductance Ca2+-activated K+ channels by WNK4 kinase. Am J Physiol Cell Physiol. 2013;305(8):C846-53.

Neal MD, Jia H, Eyer B, Good M, Guerriero CJ, Sodhi CP, Afrazi A, Prindle T Jr, Ma C, Branca M, Ozolek J, Brodsky JL, Wipf P, Hackam DJ. Discovery and validation of a new class of small molecule Toll-like receptor 4 (TLR4) inhibitors. PLoS One. 2013;8(6):e65779

CT Chu, J Ji, RK Dagda, JF Jiang, YY Tyurina, AA Kapralov, VA Tyurin, N Yanamala, IH Shrivastava, D Mohammadyani, KZQ Wang, J Zhu, J Klein-Seetharaman, K Balasubramanian, AA Amoscato, G Borisenko, Z Huang, AM Gusdon, A Cheikhi, EK Steer, R Wang, C Baty, S Watkins, I Bahar, H Bayır & VE Kagan Cardiolipin externalization to the outer mitochondrial membrane acts as an elimination signal for mitophagy in neuronal cells. Nature Cell Biol 2013; 15:1197-1205

Buck TM, Plavchak L, Roy A, Donnelly BF, Kashlan OB, Kleyman TR, Subramanya AR, Brodsky JL. The Lhs1/GRP170 chaperones facilitate the endoplasmic reticulum-associated degradation of the epithelial sodium channel. J Biol Chem. 2013;288(25):18366-80

Kar, K., Hoop, C.L., Drombosky, K.W., Baker, M.A., Kodali, R., Arduini, I., van der Wel, P.C.A., Horne, W.S., & Wetzel, R., b-hairpin-mediated nucleation of polyglutamine amyloid formation.  J. Mol. Biol. 2013; 425: 1183-1197

Donnelly BF, Needham PG, Snyder AC, Roy A, Khadem S, Brodsky JL, Subramanya AR. Hsp70 and Hsp90 multichaperone complexes sequentially regulate thiazide-sensitive cotransporter endoplasmic reticulum-associated degradation and biogenesis. J Biol Chem. 2013;288(18):13124-35

Kilpatrick K, Novoa JA, Hancock T, Guerriero CJ, Wipf P, Brodsky JL, Segatori L. Chemical induction of Hsp70 reduces α-synuclein aggregation in neuroglioma cells. ACS Chem Biol. 2013;8(7):1460-8

2012

Seguin SP, Ireland AW, Gupta T, Wright CM, Miyata Y, Wipf P, Pipas JM, Gestwicki JE, Brodsky JL. A screen for modulators of large T antigen's ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication. Antiviral Res. 2012;96(1):70-81

Jayaraman, M., Mishra, R., Kodali, R., Thakur, A.K., Koharudin, L.M.I., Gronenborn, A.M., & Wetzel, R., Kinetically competing huntingtin aggregation pathways control amyloid polymorphism and properties. Biochem. 2012; 51: 2706-2716

Liu L, Byeon IJ, Bahar I, Gronenborn AM. Domain swapping proceeds via complete unfolding: A 19F- and 1H- NMR study of the cyanovirin-N protein. J Am Chem Soc 2012; 134: 4229-35

Mishra, Rakesh, Cody L Hoop, Ravindra Kodali, Bankanidhi Sahoo, Patrick C A van der Wel, and Ronald Wetzel.  “Serine Phosphorylation Suppresses Huntingtin Amyloid Accumulation by Altering Protein Aggregation Properties.” J Mol Biol 2012; 424: 1–14.

2011

Braunstein MJ, Scott SS, Scott CM, Behrman S, Walter P, Wipf P, Coplan JD, Chrico W, Joseph D, Brodsky JL, Batuman O. Antimyeloma Effects of the Heat Shock Protein 70 Molecular Chaperone Inhibitor MAL3-101. J Oncol. 2011; 2011:232037

X Hu, Z Weng, CT Chu, L Zhang, G Cao, Y Gao, A Signore, J Zhu, T Hastings, JT Greenamyre & J Chen. Peroxiredoxin-2 protects against 6-hydroxydopamine-induced dopaminergic neurodegeneration via attenuation of the ASK1 signaling cascade.  J. Neurosci. 2011; 31: 247-261

Needham PG, Mikoluk K, Dhakarwal P, Khadem S, Snyder AC, Subramanya ARBrodsky JL. The thiazide-sensitive NaCl cotransporter is targeted for chaperone-dependent endoplasmic reticulum-associated degradation. J Biol Chem. 2011;286(51):43611-21

Sivanandam, V.N., Jayaraman, M., Hoop, C.L., Kodali, R., Wetzel, R., & van der Wel, P.C.A., The aggregation-enhancing Huntingtin N-terminus is helical in amyloid fibrils.  J. Amer. Chem. Soc. 2011; 133: 4558-4566

Huryn DM, Brodsky JL, Brummond KM, Chambers PG, Eyer B, Ireland AW, Kawasumi M, Laporte MG, Lloyd K, Manteau B, Nghiem P, Quade B, Seguin SP, Wipf P. Chemical methodology as a source of small-molecule checkpoint inhibitors and heat shock protein 70 (Hsp70) modulators. Proc Natl Acad Sci U S A. 2011;108(17):6757-62

VS Van Laar, BA Arnold, SJ Cassady, CT Chu, EA Burton & SB Berman. Bioenergetics of neurons inhibit the translocation response of Parkin following rapid mitochondrial depolarization.  Hum Mol Genet 2011; 20: 927-940

Liu L, Gronenborn AM, Bahar I. Longer simulations sample larger subspaces of conformations while maintaining robust mechanisms of motion. Proteins 2011; 80: 616-625

Botha M, Chiang AN, Needham PG, Stephens LL, Hoppe HC, Külzer S, Przyborski JM, Lingelbach K, Wipf P, Brodsky JL, Shonhai A, Blatch GL. Plasmodium falciparum encodes a single cytosolic type I Hsp40 that functionally interacts with Hsp70 and is upregulated by heat shock. Cell Stress Chaperones. 2011;16(4):389-401

Cannon JR, Sew T, Montero L, Burton EA and Greenamyre JT, Pseudotype-dependent lentiviral transduction of astrocytes or neurons in the rat substantia nigra, Exp Neurol. 2011; 228:41-52

Peters KW, Okiyoneda T, Balch WE, Braakman I, Brodsky JL, Guggino WB, Penland CM, Pollard HB, Sorscher EJ, Skach WR, Thomas PJ, Lukacs GL, Frizzell RA. CFTR Folding Consortium: methods available for studies of CFTR folding and correction. Methods Mol Biol. 2011; 742:335-53

Horowitz MP, Milanese C, Di Maio R, Hu X, Montero LM, Sanders LH, Tapias V, Sepe S, van Capellen WA, Burton EA, Greenamyre JT, and Mastroberardino PG. Single-cell redox imaging demonstrates a distinctive response of dopaminergic neurons to oxidative insults, Antioxidants & Redox Signaling 2011; 15:855-71

2010

Wisén S, Bertelsen EB, Thompson AD, Patury S, Ung P, Chang L, Evans CG, Walter GM, Wipf P, Carlson HA, Brodsky JL, Zuiderweg ER, Gestwicki JE. Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40. ACS Chem Biol. 2010;5(6):611-22

Buck TM, Kolb AR, Boyd CR, Kleyman TR, Brodsky JL. The endoplasmic reticulum-associated degradation of the epithelial sodium channel requires a unique complement of molecular chaperones. Mol Biol Cell. 2010;21(6):1047-58

2009

Wright CM, Seguin SP, Fewell SW, Zhang H, Ishwad C, Vats A, Lingwood CA, Wipf P, Fanning E, Pipas JM, Brodsky JL. Inhibition of Simian Virus 40 replication by  targeting the molecular chaperone function and ATPase activity of T antigen. Virus Res. 2009;141(1):71-80

Thakur, A. K., Jayaraman, M., Mishra, R., Thakur, M., Chellgren, V. M., Byeon, I.-J., Anjum, D. H., Kodali, R., Creamer, T. P., Conway, J. F., Gronenborn, A. M., & Wetzel, R., Polyglutamine disruption of the huntingtin exon1 N-terminus triggers a complex aggregation mechanism.  Nature Str. Mol. Biol., 2009; 16: 380-389

Patham B, Duffy J, Lane A, Davis RC, Wipf P, Fewell SW, Brodsky JL, Mensa-Wilmot K. Post-translational import of protein into the endoplasmic reticulum of a trypanosome: an in vitro system for discovery of anti-trypanosomal chemical entities. Biochem J. 2009;419(2):507-17

Liu L, Koharudin LM, Gronenborn AM, Bahar I, A comparative analysis of the equilibrium dynamics of a designed protein inferred from NMR, X-ray, and computations Proteins 2009; 77: 927-939

Chiang AN, Valderramos JC, Balachandran R, Chovatiya RJ, Mead BP, Schneider C, Bell SL, Klein MG, Huryn DM, Chen XS, Day BW, Fidock DA, Wipf P, Brodsky JL. Select pyrimidinones inhibit the propagation of the malarial parasite, Plasmodium falciparum. Bioorg Med Chem. 2009;17(4):1527-33

PG Mastroberardino, EK Hoffman, MP Horowitz, R Betarbet, G Taylor, D Cheng, HM Na, CA Gutekunst, M Gearing, JQ Trojanowski, M Anderson, CT Chu, J Peng, JT Greenamyre. A novel transferrin/TfR2-mediated mitochondrial iron transport system is disrupted in Parkinson's disease.  Neurobiol Dis 2009; 34:417-431

H Bayir, A Kapralov, J Jiang, Z Huang, YY Tyurina, VA Tyurin, Q Zhao, NA Belikova, II Vlasova, A Maeda, J Zhu, HM Na, PG Mastroberardino, LJ Sparvero, AA Amoscato, CT Chu, JT Greenamyre & VE Kagan Peroxidase mechanism of lipid dependent cross-linking of synuclein with cytochrome c: Protection against apoptosis versus delayed oxidative stress in Parkinson disease. J Biol Chem 2009; 284: 15951-15969

2008

Rabu C, Wipf P, Brodsky JL, High S. A precursor-specific role for Hsp40/Hsc70 during tail-anchored protein integration at the endoplasmic reticulum. J Biol Chem. 2008;283(41):27504-13

Myerburg MM, McKenna EE, Luke CJ, Frizzell RA, Kleyman TR, Pilewski JM. Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis. Am J Physiol Lung Cell Mol Physiol. 2008;294(5):L932-41.

Wright CM, Chovatiya RJ, Jameson NE, Turner DM, Zhu G, Werner S, Huryn DM, Pipas JM, Day BW, Wipf P, Brodsky JL. Pyrimidinone-peptoid hybrid molecules with distinct effects on molecular chaperone function and cell proliferation. Bioorg Med Chem. 2008;16(6):3291-301

Bakan, A.; Lazo, J. S.; Wipf, P.; Brummond, K. M.; Bahar, I., Toward a molecular understanding of the interaction of dual specificity phosphatases with substrates: Insights from structure-based modeling and high throughput screening. Curr. Med. Chem. 2008; 15, 2536-2544

2007

Rodina A, Vilenchik M, Moulick K, Aguirre J, Kim J, Chiang A, Litz J, Clement CC, Kang Y, She Y, Wu N, Felts S, Wipf P, Massague J, Jiang X, Brodsky JL, Krystal GW, Chiosis G. Selective compounds define Hsp90 as a major inhibitor of apoptosis in small-cell lung cancer. Nat Chem Biol. 2007;3(8):498-507

Kashlan OB, Mueller GM, Qamar MZ, Poland PA, Ahner A, Rubenstein RC, Hughey RP, Brodsky JL, Kleyman TR. Small heat shock protein alphaA-crystallin regulates  epithelial sodium channel expression. J Biol Chem. 2007;282(38):28149-56

Yang L-W, Eyal E, Chennubhotla C, JunGoo J, Gronenborn AM, Bahar I, Insights into Equilibrium Dynamics of Proteins from Comparison of NMR and X-ray Data with Computational Predictions Structure 2007; 15: 741-749

Ahner A, Nakatsukasa K, Zhang H, Frizzell RA, Brodsky JL. Small heat-shock proteins select deltaF508-CFTR for endoplasmic reticulum-associated degradation. Mol Biol Cell. 2007;18(3):806-14

Iyer, AK, Tran KT, Borysenko CW, Cascio M, Camacho CJ, Blair HC, Bahar I, Wells AJ Tenascin cytotactin epidermal growth factor-like repeat binds epidermal growth factor receptor with low affinity J Cell Physiol 2007; 211: 748-58

Bai Q, Garver JA, Hukriede NA, Burton EA. Generation of a transgenic zebrafish model of Tauopathy using a novel promoter element derived from the zebrafish eno2 gene. Nucleic Acids Res. 2007;35(19):6501-16.

2006

Zhang H, Schmidt BZ, Sun F, Condliffe SB, Butterworth MB, Youker RT, Brodsky JL, Aridor M, Frizzell RA. Cysteine string protein monitors late steps in cystic fibrosis transmembrane conductance regulator biogenesis. J Biol Chem. 2006;281(16):11312-21

Wang H, Traub LM, Weixel KM, Hawryluk MJ, Shah N, Edinger RS, Perry CJ, Kester L, Butterworth MB, Peters KW, Kleyman TR, Frizzell RA, Johnson JP. Clathrin-mediated endocytosis of the epithelial sodium channel. Role of epsin. J Biol Chem. 2006 May 19;281(20):14129-35.

Myerburg MM, Butterworth MB, McKenna EE, Peters KW, Frizzell RA, Kleyman TR, Pilewski JM. Airway surface liquid volume regulates ENaC by altering the serine protease-protease inhibitor balance: a mechanism for sodium hyperabsorption in cystic fibrosis. J Biol Chem. 2006;281(38):27942-9.

2004

Fewell SW, Smith CM, Lyon MA, Dumitrescu TP, Wipf P, Day BW, Brodsky JL. Small molecule modulators of endogenous and co-chaperone-stimulated Hsp70 ATPase activity. J Biol Chem. 2004;279(49):51131-40

Brisson, M.; Nguyen, T.; Vogt, A.; Yalowich, J.; Giorgianni, A.; Tobi, D.; Bahar, I.; Stephenson Corey, R. J.; Wipf, P.; Lazo John, S., Discovery and characterization of novel small molecule inhibitors of human cdc25b dual specificity phosphatase. Mol. Pharmacol. 2004; 66, 824-833