Jason Gestwicki, PhD

Professor
Pharmaceutical Chemistry
+1 415 502-7121

The Gestwicki Laboratory is interested in molecular chaperones, protein homeostasis and protein misfolding disorders. To approach the big questions in this area, we use a chemical biology strategy that includes the discovery and optimization of new chemical inhibitors. We use these chemical probes to acutely perturb chaperone functions, revealing how these systems normally protect from cancer and neurodegeneration. Many of our chemical probes target allosteric and protein-protein interaction sites on the molecular chaperones and we have a significant interest in discovering inhibitors of "difficult" targets. We hope to better understand the logic of protein folding and misfolding and use this information to design more effective therapies.

Publications: 

Plexin D1 emerges as a novel target in the development of neural lineage plasticity in treatment-resistant prostate cancer.

Research square

Liu C, Chen B, Xu P, Yang J, Nip C, Wang L, Shen Y, Ning S, Shang Y, Corey E, Gao AC, Gestwicki J, Wei Q, Liu L

Plasmodium falciparum heat shock proteins as anti-malarial drug targets: An update.

Cell stress & chaperones

Ahmad T, Alhammadi BA, Almaazmi SY, Arafa S, Blatch GL, Dutta T, Gestwicki JE, Keyzers RA, Shonhai A, Singh H

A missense mutation in the Hspa8 gene encoding heat shock cognate protein 70 causes neuroaxonal dystrophy in rats.

Frontiers in neuroscience

Tanaka M, Fujikawa R, Sekiguchi T, Hernandez J, Johnson OT, Tanaka D, Kumafuji K, Serikawa T, Hoang Trung H, Hattori K, Mashimo T, Kuwamura M, Gestwicki JE, Kuramoto T

Stress Biology: Complexity and Multifariousness in Health and Disease.

Cell stress & chaperones

Mayer MP, Blair L, Blatch GL, Borges TJ, Chadli A, Chiosis G, de Thonel A, Dinkova-Kostova A, Ecroyd H, Edkins AL, Eguchi T, Fleshner M, Foley KP, Fragkostefanakis S, Gestwicki J, Goloubinoff P, Heritz JA, Heske CM, Hibshman JD, Joutsen J, Li W, Lynes M, Mendillo ML, Mivechi N, Mokoena F, Okusha Y, Prahlad V, Repasky E, Sannino S, Scalia F, Shalgi R, Sistonen L, Sontag E, van Oosten-Hawle P, Vihervaara A, Wickramaratne A, Wang SXY, Zininga T

J-domain proteins: From molecular mechanisms to diseases.

Cell stress & chaperones

Marszalek J, De Los Rios P, Cyr D, Mayer MP, Adupa V, Andréasson C, Blatch GL, Braun JEA, Brodsky JL, Bukau B, Chapple JP, Conz C, Dementin S, Genevaux P, Genest O, Goloubinoff P, Gestwicki J, Hammond CM, Hines JK, Ishikawa K, Joachimiak LA, Kirstein J, Liberek K, Mokranjac D, Nillegoda N, Ramos CHI, Rebeaud M, Ron D, Rospert S, Sahi C, Shalgi R, Tomiczek B, Ushioda R, Ustyantseva E, Ye Y, Zylicz M, Kampinga HH

Cholesterol Dysregulation Drives Seed-Dependent Tau Aggregation in Patient Stem Cell-Derived Models of Tauopathy.

bioRxiv : the preprint server for biology

Lam M, Kuo SY, Reis S, Gestwicki JE, Silva MC, Haggarty SJ

Protocol for performing and optimizing differential scanning fluorimetry experiments.

STAR protocols

Wu T, Hornsby M, Zhu L, Yu JC, Shokat KM, Gestwicki JE

De novo designed Hsp70 activator dissolves intracellular condensates.

bioRxiv : the preprint server for biology

Zhang JZ, Greenwood N, Hernandez J, Cuperus JT, Huang B, Ryder BD, Queitsch C, Gestwicki JE, Baker D

Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP.

bioRxiv : the preprint server for biology

Nadel CM, Wucherer K, Oehler A, Thwin AC, Basu K, Callahan MD, Southworth DR, Mordes DA, Craik CS, Gestwicki JE

An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3.

JACC. Basic to translational science

Thompson AD, Wagner MJ, Rodriguez J, Malhotra A, Vander Roest S, Lilienthal U, Shao H, Vignesh M, Weber K, Yob JM, Prosser BL, Helms AS, Gestwicki JE, Ginsburg D, Day SM

The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT).

Journal of molecular biology

Nadel CM, Thwin AC, Callahan M, Lee K, Connelly E, Craik CS, Southworth DR, Gestwicki JE

Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly.

bioRxiv : the preprint server for biology

Braxton JR, Shao H, Tse E, Gestwicki JE, Southworth DR

Mitoribosome sensitivity to HSP70 inhibition uncovers metabolic liabilities of castration-resistant prostate cancer.

PNAS nexus

Echtenkamp FJ, Ishida R, Rivera-Marquez GM, Maisiak M, Johnson OT, Shrimp JH, Sinha A, Ralph SJ, Nisbet I, Cherukuri MK, Gestwicki JE, Neckers LM

A Comprehensive Enumeration of the Human Proteostasis Network. 2. Components of the Autophagy-Lysosome Pathway.

bioRxiv : the preprint server for biology

Proteostasis Consortium, Overall coordination, Elsasser S, Elia LP, Morimoto RI, Powers ET, Harvard Medical School group, Elsasser S, Finley D, University of California, San Francisco and Gladstone Institutes group I, Costa B, Budron M, Tokuno Z, Wang S, Iyer RG, Barth B, Mockler E, Elia LP, Finkbeiner S, University of California, San Francisco group II, Gestwicki JE, Northwestern University group, Richardson RAK, Stoeger T, Morimoto RI, Scripps Research Institute group, Tan EP, Xiao Q, Cole CM, Massey LEA, Garza D, Powers ET, Kelly JW, Stanford University group, Rainbolt TK, Chou CC, Masto VB, Frydman J, New York University group, Nixon RA

Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models.

Pharmacological research

Xu P, Yang JC, Ning S, Chen B, Nip C, Wei Q, Liu L, Johnson OT, Gao AC, Gestwicki JE, Evans CP, Liu C

Chemical Features of Polyanions Modulate Tau Aggregation and Conformational States.

Journal of the American Chemical Society

Montgomery KM, Carroll EC, Thwin AC, Quddus AY, Hodges P, Southworth DR, Gestwicki JE

Conformationally responsive dyes enable protein-adaptive differential scanning fluorimetry.

bioRxiv : the preprint server for biology

Wu T, Yu JC, Suresh A, Gale-Day ZJ, Alteen MG, Woo AS, Millbern Z, Johnson OT, Carroll EC, Partch CL, Fourches D, Vinueza NR, Vocadlo DJ, Gestwicki JE

Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2.

Proceedings of the National Academy of Sciences of the United States of America

Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko DS, Moroz YS, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS

N-myc-Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma.

Cancer research

Kuzuoglu-Ozturk D, Aksoy O, Schmidt C, Lea R, Larson JD, Phelps RRL, Nasholm N, Holt M, Contreras A, Huang M, Wong-Michalak S, Shao H, Wechsler-Reya R, Phillips JJ, Gestwicki JE, Ruggero D, Weiss WA

Structure-based inhibitor optimization for the Nsp3 Macrodomain of SARS-CoV-2.

bioRxiv : the preprint server for biology

Gahbauer S, Correy GJ, Schuller M, Ferla MP, Doruk YU, Rachman M, Wu T, Diolaiti M, Wang S, Neitz RJ, Fearon D, Radchenko D, Moroz Y, Irwin JJ, Renslo AR, Taylor JC, Gestwicki JE, von Delft F, Ashworth A, Ahel I, Shoichet BK, Fraser JS

Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma.

Cell chemical biology

Ferguson ID, Lin YT, Lam C, Shao H, Tharp KM, Hale M, Kasap C, Mariano MC, Kishishita A, Patiño Escobar B, Mandal K, Steri V, Wang D, Phojanakong P, Tuomivaara ST, Hann B, Driessen C, Van Ness B, Gestwicki JE, Wiita AP

A campaign targeting a conserved Hsp70 binding site uncovers how subcellular localization is linked to distinct biological activities.

Cell chemical biology

Shao H, Taguwa S, Gilbert L, Shkedi A, Sannino S, Guerriero CJ, Gale-Day ZJ, Young ZT, Brodsky JL, Weissman J, Gestwicki JE, Frydman J

Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate.

Nature communications

Carrettiero DC, Almeida MC, Longhini AP, Rauch JN, Han D, Zhang X, Najafi S, Gestwicki JE, Kosik KS

Multi-protein complexes as drug targets.

Cell chemical biology

Gestwicki JE

Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy.

Nature communications

Wang C, Fan L, Khawaja RR, Liu B, Zhan L, Kodama L, Chin M, Li Y, Le D, Zhou Y, Condello C, Grinberg LT, Seeley WW, Miller BL, Mok SA, Gestwicki JE, Cuervo AM, Luo W, Gan L

The YΦ motif defines the structure-activity relationships of human 20S proteasome activators.

Nature communications

Opoku-Nsiah KA, de la Pena AH, Williams SK, Chopra N, Sali A, Lander GC, Gestwicki JE

Two distinct classes of co-chaperones compete for the EEVD motif in heat shock protein 70 (Hsp70) to tune its chaperone activities.

The Journal of biological chemistry

Johnson OT, Nadel CM, Carroll EC, Arhar T, Gestwicki JE

Selective vulnerabilities in the proteostasis network of castration-resistant prostate cancer.

Cell chemical biology

Shkedi A, Taylor IR, Echtenkamp F, Ramkumar P, Alshalalfa M, Rivera-Márquez GM, Moses MA, Shao H, Karnes RJ, Neckers L, Feng F, Kampmann M, Gestwicki JE

Analogs of the Heat Shock Protein 70 Inhibitor MKT-077 Suppress Medullary Thyroid Carcinoma Cells.

International journal of molecular sciences

Hong SK, Starenki D, Johnson OT, Gestwicki JE, Park JI

The interactions of molecular chaperones with client proteins: why are they so weak?

The Journal of biological chemistry

Arhar T, Shkedi A, Nadel CM, Gestwicki JE

Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells.

Journal of medicinal chemistry

Shkedi A, Adkisson M, Schroeder A, Eckalbar WL, Kuo SY, Neckers L, Gestwicki JE

The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state.

Molecular cell

Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR

Adhesion-mediated mechanosignaling forces mitohormesis.

Cell metabolism

Tharp KM, Higuchi-Sanabria R, Timblin GA, Ford B, Garzon-Coral C, Schneider C, Muncie JM, Stashko C, Daniele JR, Moore AS, Frankino PA, Homentcovschi S, Manoli SS, Shao H, Richards AL, Chen KH, Hoeve JT, Ku GM, Hellerstein M, Nomura DK, Saijo K, Gestwicki J, Dunn AR, Krogan NJ, Swaney DL, Dillin A, Weaver VM

Functional genomics screen identifies proteostasis targets that modulate prion protein (PrP) stability.

Cell stress & chaperones

Abrams J, Arhar T, Mok SA, Taylor IR, Kampmann M, Gestwicki JE

Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking.

bioRxiv : the preprint server for biology

Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Martins LC, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, Aimon A, Bennett JM, Neto JB, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs M, Gorrie-Stone TJ, Holton JM, Johnson MG, Krojer T, Meigs G, Powell AJ, Rack JGM, Rangel VL, Russi S, Skyner RE, Smith CA, Soares AS, Wierman JL, Zhu K, Jura N, Ashworth A, Irwin J, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I

A Phosphoramidate Strategy Enables Membrane Permeability of a Non-nucleotide Inhibitor of the Prolyl Isomerase Pin1.

ACS medicinal chemistry letters

Schwarz DMC, Williams SK, Dillenburg M, Wagner CR, Gestwicki JE

Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy.

The Journal of clinical investigation

Bengoechea R, Findlay AR, Bhadra AK, Shao H, Stein KC, Pittman SK, Daw J, Gestwicki JE, True HL, Weihl CC

A novel radioligand reveals tissue specific pharmacological modulation of glucocorticoid receptor expression with positron emission tomography.

ACS chemical biology

Huang Y, Zhao N, Wang YH, Truillet C, Wei J, Blecha JE, VanBrocklin HF, Seo Y, Sayeed M, Feldman BJ, Aggarwal R, Behr SC, Shao H, Wilson DM, Villanueva-Meyer JE, Gestwicki JE, Evans MJ

Mortalin/HSPA9 targeting selectively induces KRAS tumor cell death by perturbing mitochondrial membrane permeability.

Oncogene

Wu PK, Hong SK, Starenki D, Oshima K, Shao H, Gestwicki JE, Tsai S, Park JI

Pharmacologic dissection of the overlapping impact of heat shock protein family members on platelet function.

Journal of thrombosis and haemostasis : JTH

Jackson JW, Rivera-Marquez G, Beebe K, Tran AD, Trepel JB, Gestwicki JE, Blagg BSJ, Ohkubo S, Neckers LM

Mortalin (HSPA9) facilitates BRAF-mutant tumor cell survival by suppressing ANT3-mediated mitochondrial membrane permeability.

Science signaling

Wu PK, Hong SK, Chen W, Becker AE, Gundry RL, Lin CW, Shao H, Gestwicki JE, Park JI

Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone.

Cell chemical biology

Singh JK, Hutt DM, Tait B, Guy NC, Sivils JC, Ortiz NR, Payan AN, Komaragiri SK, Owens JJ, Culbertson D, Blair LJ, Dickey C, Kuo SY, Finley D, Dyson HJ, Cox MB, Chaudhary J, Gestwicki JE, Balch WE

Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98.

Bioorganic & medicinal chemistry letters

Shao H, Gestwicki JE

Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells.

Chemical science

Taylor IR, Assimon VA, Kuo SY, Rinaldi S, Li X, Young ZT, Morra G, Green K, Nguyen D, Shao H, Garneau-Tsodikova S, Colombo G, Gestwicki JE

Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.

Molecular neurodegeneration

Chen X, Li Y, Wang C, Tang Y, Mok SA, Tsai RM, Rojas JC, Karydas A, Miller BL, Boxer AL, Gestwicki JE, Arkin M, Cuervo AM, Gan L

Individualized Management of Genetic Diversity in Niemann-Pick C1 through Modulation of the Hsp70 Chaperone System.

Human molecular genetics

Wang C, Scott SM, Sun S, Zhao P, Hutt DM, Shao H, Gestwicki JE, Balch WE

End-Binding E3 Ubiquitin Ligases Enable Protease Signaling.

ACS chemical biology

Ravalin M, Basu K, Gestwicki JE, Craik CS

Author Correction: Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.

Nature communications

Eftekharzadeh B, Banduseela VC, Chiesa G, Martínez-Cristóbal P, Rauch JN, Nath SR, Schwarz DMC, Shao H, Marin-Argany M, Di Sanza C, Giorgetti E, Yu Z, Pierattelli R, Felli IC, Brun-Heath I, García J, Nebreda ÁR, Gestwicki JE, Lieberman AP, Salvatella X

Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation.

The Journal of biological chemistry

Chen JJ, Nathaniel DL, Raghavan P, Nelson M, Tian R, Tse E, Hong JY, See SK, Mok SA, Hein MY, Southworth DR, Grinberg LT, Gestwicki JE, Leonetti MD, Kampmann M

Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis.

Neuron

Sohn PD, Huang CT, Yan R, Fan L, Tracy TE, Camargo CM, Montgomery KM, Arhar T, Mok SA, Freilich R, Baik J, He M, Gong S, Roberson ED, Karch CM, Gestwicki JE, Xu K, Kosik KS, Gan L

Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor.

Nature communications

Eftekharzadeh B, Banduseela VC, Chiesa G, Martínez-Cristóbal P, Rauch JN, Nath SR, Schwarz DMC, Shao H, Marin-Argany M, Di Sanza C, Giorgetti E, Yu Z, Pieratelli R, Felli IC, Brun-Heath I, García J, Nebreda ÁR, Gestwicki JE, Lieberman AP, Salvatella X

Mechanism of Action of VP1-001 in cryAB(R120G)-Associated and Age-Related Cataracts.

Investigative ophthalmology & visual science

Molnar KS, Dunyak BM, Su B, Izrayelit Y, McGlasson-Naumann B, Hamilton PD, Qian M, Covey DF, Gestwicki JE, Makley LN, Andley UP

Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases.

Nature chemical biology

Ravalin M, Theofilas P, Basu K, Opoku-Nsiah KA, Assimon VA, Medina-Cleghorn D, Chen YF, Bohn MF, Arkin M, Grinberg LT, Craik CS, Gestwicki JE

Correction: The pleiotropic effects of TNFa in breast cancer subtypes is regulated by TNFAIP3/A20.

Oncogene

Lee E, Ouzounova M, Piranlioglu R, Ma MT, Guzel M, Marasco D, Chadli A, Gestwicki JE, Cowell JK, Wicha MS, Hassan KA, Korkaya H

A Legionella pneumophila Kinase Phosphorylates the Hsp70 Chaperone Family to Inhibit Eukaryotic Protein Synthesis.

Cell host & microbe

Moss SM, Taylor IR, Ruggero D, Gestwicki JE, Shokat KM, Mukherjee S

Zika Virus Dependence on Host Hsp70 Provides a Protective Strategy against Infection and Disease.

Cell reports

Taguwa S, Yeh MT, Rainbolt TK, Nayak A, Shao H, Gestwicki JE, Andino R, Frydman J

Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks.

Nature communications

Meister-Broekema M, Freilich R, Jagadeesan C, Rauch JN, Bengoechea R, Motley WW, Kuiper EFE, Minoia M, Furtado GV, van Waarde MAWH, Bird SJ, Rebelo A, Zuchner S, Pytel P, Scherer SS, Morelli FF, Carra S, Weihl CC, Bergink S, Gestwicki JE, Kampinga HH

Predicting protein targets for drug-like compounds using transcriptomics.

PLoS computational biology

Pabon NA, Xia Y, Estabrooks SK, Ye Z, Herbrand AK, Süß E, Biondi RM, Assimon VA, Gestwicki JE, Brodsky JL, Camacho CJ, Bar-Joseph Z

Function, evolution, and structure of J-domain proteins.

Cell stress & chaperones

Kampinga HH, Andreasson C, Barducci A, Cheetham ME, Cyr D, Emanuelsson C, Genevaux P, Gestwicki JE, Goloubinoff P, Huerta-Cepas J, Kirstein J, Liberek K, Mayer MP, Nagata K, Nillegoda NB, Pulido P, Ramos C, De Los Rios P, Rospert S, Rosenzweig R, Sahi C, Taipale M, Tomiczek B, Ushioda R, Young JC, Zimmermann R, Zylicz A, Zylicz M, Craig EA, Marszalek J

A Local Allosteric Network in Heat Shock Protein 70 (Hsp70) Links Inhibitor Binding to Enzyme Activity and Distal Protein-Protein Interactions.

ACS chemical biology

Rinaldi S, Assimon VA, Young ZT, Morra G, Shao H, Taylor IR, Gestwicki JE, Colombo G

Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau.

Nature communications

Freilich R, Betegon M, Tse E, Mok SA, Julien O, Agard DA, Southworth DR, Takeuchi K, Gestwicki JE

Inhibitors and chemical probes for molecular chaperone networks.

The Journal of biological chemistry

Gestwicki JE, Shao H

The pleiotropic effects of TNFa in breast cancer subtypes is regulated by TNFAIP3/A20.

Oncogene

Lee E, Ouzounova M, Piranlioglu R, Ma MT, Guzel M, Marasco D, Chadli A, Gestwicki JE, Cowell JK, Wicha MS, Hassan KA, Korkaya H

KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice.

Science translational medicine

Polson ES, Kuchler VB, Abbosh C, Ross EM, Mathew RK, Beard HA, da Silva B, Holding AN, Ballereau S, Chuntharpursat-Bon E, Williams J, Griffiths HBS, Shao H, Patel A, Davies AJ, Droop A, Chumas P, Short SC, Lorger M, Gestwicki JE, Roberts LD, Bon RS, Allison SJ, Zhu S, Markowetz F, Wurdak H

Exploration of Benzothiazole-Rhodacyanines as Allosteric Inhibitors of Protein-Protein Interactions with Heat Shock Protein 70 (Hsp70).

Journal of medicinal chemistry

Shao H, Li X, Moses MA, Gilbert LA, Kalyanaraman C, Young ZT, Chernova M, Journey SN, Weissman JS, Hann B, Jacobson MP, Neckers LM, Gestwicki JE

Aim for the core: suitability of the ubiquitin-independent 20S proteasome as a drug target in neurodegeneration.

Translational research : the journal of laboratory and clinical medicine

Opoku-Nsiah KA, Gestwicki JE

HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C.

JCI insight

Glazier AA, Hafeez N, Mellacheruvu D, Basrur V, Nesvizhskii AI, Lee LM, Shao H, Tang V, Yob JM, Gestwicki JE, Helms AS, Day SM

Revisiting the "Art of the Chemical Probe".

ACS chemical biology

Schwarz DMC, Gestwicki JE

Targeting the Hsp40/Hsp70 chaperone axis as a novel strategy to treat castration-resistant prostate cancer.

Cancer research

Moses MA, Kim YS, Rivera-Marquez GM, Oshima N, Watson MJ, Beebe K, Wells C, Lee S, Zuehlke AD, Shao H, Bingman WE, Kumar V, Malhotra S, Weigel NL, Gestwicki JE, Trepel J, Neckers LM

The disorderly conduct of Hsc70 and its interaction with the Alzheimer's related Tau protein.

The Journal of biological chemistry

Taylor IR, Ahmad A, Wu T, Nordhues BA, Bhullar A, Gestwicki JE, Zuiderweg ERP

Mapping interactions with the chaperone network reveals factors that protect against tau aggregation.

Nature structural & molecular biology

Mok SA, Condello C, Freilich R, Gillies A, Arhar T, Oroz J, Kadavath H, Julien O, Assimon VA, Rauch JN, Dunyak BM, Lee J, Tsai FTF, Wilson MR, Zweckstetter M, Dickey CA, Gestwicki JE

Protein cross-linking capillary electrophoresis at increased throughput for a range of protein-protein interactions.

The Analyst

Ouimet CM, Dawod M, Grinias J, Assimon VA, Lodge J, Mapp AK, Gestwicki JE, Kennedy RT

Rational design and screening of peptide-based inhibitors of heat shock factor 1 (HSF1).

Bioorganic & medicinal chemistry

Ran X, Burchfiel ET, Dong B, Rettko NJ, Dunyak BM, Shao H, Thiele DJ, Gestwicki JE

Protein-Protein Interactions in the Molecular Chaperone Network.

Accounts of chemical research

Freilich R, Arhar T, Abrams JL, Gestwicki JE

SIRT1 Deacetylates Tau and Reduces Pathogenic Tau Spread in a Mouse Model of Tauopathy.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Min SW, Sohn PD, Li Y, Devidze N, Johnson JR, Krogan NJ, Masliah E, Mok SA, Gestwicki JE, Gan L

High Throughput Screen for Inhibitors of Protein-Protein Interactions in a Reconstituted Heat Shock Protein 70 (Hsp70) Complex.

The Journal of biological chemistry

Taylor IR, Dunyak BM, Komiyama T, Shao H, Ran X, Assimon VA, Kalyanaraman C, Rauch JN, Jacobson MP, Zuiderweg ERP, Gestwicki JE

Therapeutic Strategies for Restoring Tau Homeostasis.

Cold Spring Harbor perspectives in medicine

Young ZT, Mok SA, Gestwicki JE

X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition.

The Journal of biological chemistry

Cesa LC, Shao H, Srinivasan SR, Tse E, Jain C, Zuiderweg ERP, Southworth DR, Mapp AK, Gestwicki JE

Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades.

Molecular cancer research : MCR

Srinivasan SR, Cesa LC, Li X, Julien O, Zhuang M, Shao H, Chung J, Maillard I, Wells JA, Duckett CS, Gestwicki JE

Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules.

Cold Spring Harbor perspectives in medicine

Rauch JN, Olson SH, Gestwicki JE

From Fuzzy to Function: The New Frontier of Protein-Protein Interactions.

Accounts of chemical research

Pricer R, Gestwicki JE, Mapp AK

The remarkable multivalency of the Hsp70 chaperones.

Cell stress & chaperones

Zuiderweg ER, Hightower LE, Gestwicki JE

BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins.

Journal of molecular biology

Rauch JN, Tse E, Freilich R, Mok SA, Makley LN, Southworth DR, Gestwicki JE

Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3.

Brain : a journal of neurology

Costa MDC, Ashraf NS, Fischer S, Yang Y, Schapka E, Joshi G, McQuade TJ, Dharia RM, Dulchavsky M, Ouyang M, Cook D, Sun D, Larsen MJ, Gestwicki JE, Todi SV, Ivanova MI, Paulson HL

Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells.

Cancer research

Gabai VL, Yaglom JA, Wang Y, Meng L, Shao H, Kim G, Colvin T, Gestwicki J, Sherman MY

Stabilizing the Hsp70-Tau Complex Promotes Turnover in Models of Tauopathy.

Cell chemical biology

Young ZT, Rauch JN, Assimon VA, Jinwal UK, Ahn M, Li X, Dunyak BM, Ahmad A, Carlson GA, Srinivasan SR, Zuiderweg ER, Dickey CA, Gestwicki JE

Protein Cross-Linking Capillary Electrophoresis for Protein-Protein Interaction Analysis.

Analytical chemistry

Ouimet CM, Shao H, Rauch JN, Dawod M, Nordhues B, Dickey CA, Gestwicki JE, Kennedy RT

Combined chemical-genetic approach identifies cytosolic HSP70 dependence in rhabdomyosarcoma.

Proceedings of the National Academy of Sciences of the United States of America

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

Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy.

The Journal of biological chemistry

Morozova K, Clement CC, Kaushik S, Stiller B, Arias E, Ahmad A, Rauch JN, Chatterjee V, Melis C, Scharf B, Gestwicki JE, Cuervo AM, Zuiderweg ER, Santambrogio L

Inhibition of Both Hsp70 Activity and Tau Aggregation in Vitro Best Predicts Tau Lowering Activity of Small Molecules.

ACS chemical biology

Martin MD, Baker JD, Suntharalingam A, Nordhues BA, Shelton LB, Zheng D, Sabbagh JJ, Haystead TA, Gestwicki JE, Dickey CA

Apratoxin Kills Cells by Direct Blockade of the Sec61 Protein Translocation Channel.

Cell chemical biology

Paatero AO, Kellosalo J, Dunyak BM, Almaliti J, Gestwicki JE, Gerwick WH, Taunton J, Paavilainen VO

Allosteric heat shock protein 70 inhibitors block hepatitis C virus assembly.

International journal of antimicrobial agents

Khachatoorian R, Riahi R, Ganapathy E, Shao H, Wheatley NM, Sundberg C, Jung CL, Ruchala P, Dasgupta A, Arumugaswami V, Gestwicki JE, French SW

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition).

Autophagy

Klionsky DJ, Abdelmohsen K, Abe A, Abedin MJ, Abeliovich H, Acevedo Arozena A, Adachi H, Adams CM, Adams PD, Adeli K, Adhihetty PJ, Adler SG, Agam G, Agarwal R, Aghi MK, Agnello M, Agostinis P, Aguilar PV, Aguirre-Ghiso J, Airoldi EM, Ait-Si-Ali S, Akematsu T, Akporiaye ET, Al-Rubeai M, Albaiceta GM, Albanese C, Albani D, Albert ML, Aldudo J, Algül H, Alirezaei M, Alloza I, Almasan A, Almonte-Beceril M, Alnemri ES, Alonso C, Altan-Bonnet N, Altieri DC, Alvarez S, Alvarez-Erviti L, Alves S, Amadoro G, Amano A, Amantini C, Ambrosio S, Amelio I, Amer AO, Amessou M, Amon A, An Z, Anania FA, Andersen SU, Andley UP, Andreadi CK, Andrieu-Abadie N, Anel A, Ann DK, Anoopkumar-Dukie S, Antonioli M, Aoki H, Apostolova N, Aquila S, Aquilano K, Araki K, Arama E, Aranda A, Araya J, Arcaro A, Arias E, Arimoto H, Ariosa AR, Armstrong JL, Arnould T, Arsov I, Asanuma K, Askanas V, Asselin E, Atarashi R, Atherton SS, Atkin JD, Attardi LD, Auberger P, Auburger G, Aurelian L, Autelli R, Avagliano L, Avantaggiati ML, Avrahami L, Awale S, Azad N, Bachetti T, Backer JM, Bae DH, Bae JS, Bae ON, Bae SH, Baehrecke EH, Baek SH, Baghdiguian S, Bagniewska-Zadworna A, Bai H, Bai J, Bai XY, Bailly Y, Balaji KN, Balduini W, Ballabio A, Balzan R, Banerjee R, Bánhegyi G, Bao H, Barbeau B, Barrachina MD, Barreiro E, Bartel B, Bartolomé A, Bassham DC, Bassi MT, Bast RC, Basu A, Batista MT, Batoko H, Battino M, Bauckman K, Baumgarner BL, Bayer KU, Beale R, Beaulieu JF, Beck GR, Becker C, Beckham JD, Bédard PA, Bednarski PJ, Begley TJ, Behl C, Behrends C, Behrens GM, Behrns KE, Bejarano E, Belaid A, Belleudi F, Bénard G, Berchem G, Bergamaschi D, Bergami M, Berkhout B, Berliocchi L, Bernard A, Bernard M, Bernassola F, Bertolotti A, Bess AS, Besteiro S, Bettuzzi S, Bhalla S, Bhattacharyya S, Bhutia SK, Biagosch C, Bianchi MW, Biard-Piechaczyk M, Billes V, Bincoletto C, Bingol B, Bird SW, Bitoun M, Bjedov I, Blackstone C, Blanc L, Blanco GA, Blomhoff HK, Boada-Romero E, Böckler S, Boes M, Boesze-Battaglia K, Boise LH, Bolino A, Boman A, Bonaldo P, Bordi M, Bosch J, Botana LM, Botti J, Bou G, Bouché M, Bouchecareilh M, Boucher MJ, Boulton ME, Bouret SG, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady N, Braga VM, Brancolini C, Braus GH, Bravo-San Pedro JM, Brennan LA, Bresnick EH, Brest P, Bridges D, Bringer MA, Brini M, Brito GC, Brodin B, Brookes PS, Brown EJ, Brown K, Broxmeyer HE, Bruhat A, Brum PC, Brumell JH, Brunetti-Pierri N, Bryson-Richardson RJ, Buch S, Buchan AM, Budak H, Bulavin DV, Bultman SJ, Bultynck G, Bumbasirevic V, Burelle Y, Burke RE, Burmeister M, Bütikofer P, Caberlotto L, Cadwell K, Cahova M, Cai D, Cai J, Cai Q, Calatayud S, Camougrand N, Campanella M, Campbell GR, Campbell M, Campello S, Candau R, Caniggia I, Cantoni L, Cao L, Caplan AB, Caraglia M, Cardinali C, Cardoso SM, Carew JS, Carleton LA, Carlin CR, Carloni S, Carlsson SR, Carmona-Gutierrez D, Carneiro LA, Carnevali O, Carra S, Carrier A, Carroll B, Casas C, Casas J, Cassinelli G, Castets P, Castro-Obregon S, Cavallini G, Ceccherini I, Cecconi F, Cederbaum AI, Ceña V, Cenci S, Cerella C, Cervia D, Cetrullo S, Chaachouay H, Chae HJ, Chagin AS, Chai CY, Chakrabarti G, Chamilos G, Chan EY, Chan MT, Chandra D, Chandra P, Chang CP, Chang RC, Chang TY, Chatham JC, Chatterjee S, Chauhan S, Che Y, Cheetham ME, Cheluvappa R, Chen CJ, Chen G, Chen GC, Chen G, Chen H, Chen JW, Chen JK, Chen M, Chen M, Chen P, Chen Q, Chen Q, Chen SD, Chen S, Chen SS, Chen W, Chen WJ, Chen WQ, Chen W, Chen X, Chen YH, Chen YG, Chen Y, Chen Y, Chen Y, Chen YJ, Chen YQ, Chen Y, Chen Z, Chen Z, Cheng A, Cheng CH, Cheng H, Cheong H, Cherry S, Chesney J, Cheung CH, Chevet E, Chi HC, Chi SG, Chiacchiera F, Chiang HL, Chiarelli R, Chiariello M, Chieppa M, Chin LS, Chiong M, Chiu GN, Cho DH, Cho SG, Cho WC, Cho YY, Cho YS, Choi AM, Choi EJ, Choi EK, Choi J, Choi ME, Choi SI, Chou TF, Chouaib S, Choubey D, Choubey V, Chow KC, Chowdhury K, Chu CT, Chuang TH, Chun T, Chung H, Chung T, Chung YL, Chwae YJ, Cianfanelli V, et al

Targeting Allosteric Control Mechanisms in Heat Shock Protein 70 (Hsp70).

Current topics in medicinal chemistry

Li X, Shao H, Taylor IR, Gestwicki JE

Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection.

Cell

Taguwa S, Maringer K, Li X, Bernal-Rubio D, Rauch JN, Gestwicki JE, Andino R, Fernandez-Sesma A, Frydman J

Pharmacological chaperone for a-crystallin partially restores transparency in cataract models.

Science (New York, N.Y.)

Makley LN, McMenimen KA, DeVree BT, Goldman JW, McGlasson BN, Rajagopal P, Dunyak BM, McQuade TJ, Thompson AD, Sunahara R, Klevit RE, Andley UP, Gestwicki JE

Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits.

Nature medicine

Min SW, Chen X, Tracy TE, Li Y, Zhou Y, Wang C, Shirakawa K, Minami SS, Defensor E, Mok SA, Sohn PD, Schilling B, Cong X, Ellerby L, Gibson BW, Johnson J, Krogan N, Shamloo M, Gestwicki J, Masliah E, Verdin E, Gan L

Direct and Propagated Effects of Small Molecules on Protein-Protein Interaction Networks.

Frontiers in bioengineering and biotechnology

Cesa LC, Mapp AK, Gestwicki JE

Deconvolution method for specific and nonspecific binding of ligand to multiprotein complex by native mass spectrometry.

Analytical chemistry

Guan S, Trnka MJ, Bushnell DA, Robinson PJ, Gestwicki JE, Burlingame AL

The active Hsc70/tau complex can be exploited to enhance tau turnover without damaging microtubule dynamics.

Human molecular genetics

Fontaine SN, Martin MD, Akoury E, Assimon VA, Borysov S, Nordhues BA, Sabbagh JJ, Cockman M, Gestwicki JE, Zweckstetter M, Dickey CA

Isoform-selective Genetic Inhibition of Constitutive Cytosolic Hsp70 Activity Promotes Client Tau Degradation Using an Altered Co-chaperone Complement.

The Journal of biological chemistry

Fontaine SN, Rauch JN, Nordhues BA, Assimon VA, Stothert AR, Jinwal UK, Sabbagh JJ, Chang L, Stevens SM, Zuiderweg ER, Gestwicki JE, Dickey CA

Concise Synthesis of Spergualin-Inspired Molecules With Broad-Spectrum Antibiotic Activity.

MedChemComm

Assimon VA, Shao H, Garneau-Tsodikova S, Gestwicki JE

Synthesis, stereochemical analysis, and derivatization of myricanol provide new probes that promote autophagic tau clearance.

ACS chemical biology

Martin MD, Calcul L, Smith C, Jinwal UK, Fontaine SN, Darling A, Seeley K, Wojtas L, Narayan M, Gestwicki JE, Smith GR, Reitz AB, Baker BJ, Dickey CA

Validation of the Hsp70-Bag3 protein-protein interaction as a potential therapeutic target in cancer.

Molecular cancer therapeutics

Li X, Colvin T, Rauch JN, Acosta-Alvear D, Kampmann M, Dunyak B, Hann B, Aftab BT, Murnane M, Cho M, Walter P, Weissman JS, Sherman MY, Gestwicki JE

Targeting Hsp90/Hsp70-based protein quality control for treatment of adult onset neurodegenerative diseases.

Annual review of pharmacology and toxicology

Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP

Genomic heat shock element sequences drive cooperative human heat shock factor 1 DNA binding and selectivity.

The Journal of biological chemistry

Jaeger AM, Makley LN, Gestwicki JE, Thiele DJ

Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis.

Journal of neuroinflammation

Selenica ML, Davtyan H, Housley SB, Blair LJ, Gillies A, Nordhues BA, Zhang B, Liu J, Gestwicki JE, Lee DC, Gordon MN, Morgan D, Dickey CA

Rehabilitating mutant GCase.

Chemistry & biology

Rauch JN, Gestwicki JE

An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild-type and drug-resistant proteases.

Journal of medicinal chemistry

Ung PM, Dunbar JB, Gestwicki JE, Carlson HA

Hsp70-Bag3 interactions regulate cancer-related signaling networks.

Cancer research

Colvin TA, Gabai VL, Gong J, Calderwood SK, Li H, Gummuluru S, Matchuk ON, Smirnova SG, Orlova NV, Zamulaeva IA, Garcia-Marcos M, Li X, Young ZT, Rauch JN, Gestwicki JE, Takayama S, Sherman MY

A model in which heat shock protein 90 targets protein-folding clefts: rationale for a new approach to neuroprotective treatment of protein folding diseases.

Experimental biology and medicine (Maywood, N.J.)

Pratt WB, Morishima Y, Gestwicki JE, Lieberman AP, Osawa Y

High-throughput screen of natural product extracts in a yeast model of polyglutamine proteotoxicity.

Chemical biology & drug design

Walter GM, Raveh A, Mok SA, McQuade TJ, Arevang CJ, Schultz PJ, Smith MC, Asare S, Cruz PG, Wisen S, Matainaho T, Sherman DH, Gestwicki JE

The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain.

The Journal of biological chemistry

Connarn JN, Assimon VA, Reed RA, Tse E, Southworth DR, Zuiderweg ER, Gestwicki JE, Sun D

Identification of key hinge residues important for nucleotide-dependent allostery in E. coli Hsp70/DnaK.

PLoS computational biology

Ung PM, Thompson AD, Chang L, Gestwicki JE, Carlson HA

Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents.

ACS medicinal chemistry letters

Li X, Srinivasan SR, Connarn J, Ahmad A, Young ZT, Kabza AM, Zuiderweg ER, Sun D, Gestwicki JE

Development of a capillary electrophoresis platform for identifying inhibitors of protein-protein interactions.

Analytical chemistry

Rauch JN, Nie J, Buchholz TJ, Gestwicki JE, Kennedy RT

The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex.

Biochemistry

Smith MC, Scaglione KM, Assimon VA, Patury S, Thompson AD, Dickey CA, Southworth DR, Paulson HL, Gestwicki JE, Zuiderweg ER

Inhibitors of difficult protein-protein interactions identified by high-throughput screening of multiprotein complexes.

ACS chemical biology

Cesa LC, Patury S, Komiyama T, Ahmad A, Zuiderweg ERP, Gestwicki JE

CSAR data set release 2012: ligands, affinities, complexes, and docking decoys.

Journal of chemical information and modeling

Dunbar JB, Smith RD, Damm-Ganamet KL, Ahmed A, Esposito EX, Delproposto J, Chinnaswamy K, Kang YN, Kubish G, Gestwicki JE, Stuckey JA, Carlson HA

Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau.

Biological psychiatry

Abisambra J, Jinwal UK, Miyata Y, Rogers J, Blair L, Li X, Seguin SP, Wang L, Jin Y, Bacon J, Brady S, Cockman M, Guidi C, Zhang J, Koren J, Young ZT, Atkins CA, Zhang B, Lawson LY, Weeber EJ, Brodsky JL, Gestwicki JE, Dickey CA

Synthesis and initial evaluation of YM-08, a blood-brain barrier permeable derivative of the heat shock protein 70 (Hsp70) inhibitor MKT-077, which reduces tau levels.

ACS chemical neuroscience

Miyata Y, Li X, Lee HF, Jinwal UK, Srinivasan SR, Seguin SP, Young ZT, Brodsky JL, Dickey CA, Sun D, Gestwicki JE

Allostery in the Hsp70 chaperone proteins.

Topics in current chemistry

Zuiderweg ER, Bertelsen EB, Rousaki A, Mayer MP, Gestwicki JE, Ahmad A

Hsp70 protein complexes as drug targets.

Current pharmaceutical design

Assimon VA, Gillies AT, Rauch JN, Gestwicki JE

Imbalance of Hsp70 family variants fosters tau accumulation.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Jinwal UK, Akoury E, Abisambra JF, O'Leary JC, Thompson AD, Blair LJ, Jin Y, Bacon J, Nordhues BA, Cockman M, Zhang J, Li P, Zhang B, Borysov S, Uversky VN, Biernat J, Mandelkow E, Gestwicki JE, Zweckstetter M, Dickey CA

Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation.

Nature chemical biology

Wang AM, Miyata Y, Klinedinst S, Peng HM, Chua JP, Komiyama T, Li X, Morishima Y, Merry DE, Pratt WB, Osawa Y, Collins CA, Gestwicki JE, Lieberman AP

Cysteine reactivity distinguishes redox sensing by the heat-inducible and constitutive forms of heat shock protein 70.

Chemistry & biology

Miyata Y, Rauch JN, Jinwal UK, Thompson AD, Srinivasan S, Dickey CA, Gestwicki JE

Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages.

Journal of immunology (Baltimore, Md. : 1950)

Davis MJ, Gregorka B, Gestwicki JE, Swanson JA

A screen for modulators of large T antigen's ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication.

Antiviral research

Seguin SP, Ireland AW, Gupta T, Wright CM, Miyata Y, Wipf P, Pipas JM, Gestwicki JE, Brodsky JL

Analysis of the tau-associated proteome reveals that exchange of Hsp70 for Hsp90 is involved in tau degradation.

ACS chemical biology

Thompson AD, Scaglione KM, Prensner J, Gillies AT, Chinnaiyan A, Paulson HL, Jinwal UK, Dickey CA, Gestwicki JE

Fine-tuning multiprotein complexes using small molecules.

ACS chemical biology

Thompson AD, Dugan A, Gestwicki JE, Mapp AK

Molecular chaperones DnaK and DnaJ share predicted binding sites on most proteins in the E. coli proteome.

Molecular bioSystems

Srinivasan SR, Gillies AT, Chang L, Thompson AD, Gestwicki JE

Pharmacological tuning of heat shock protein 70 modulates polyglutamine toxicity and aggregation.

ACS chemical biology

Chafekar SM, Wisén S, Thompson AD, Echeverria A, Walter GM, Evans CG, Makley LN, Gestwicki JE, Duennwald ML

The C-terminal repeating units of CsgB direct bacterial functional amyloid nucleation.

Journal of molecular biology

Hammer ND, McGuffie BA, Zhou Y, Badtke MP, Reinke AA, Brännström K, Gestwicki JE, Olofsson A, Almqvist F, Chapman MR

Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein.

The Journal of biological chemistry

Jinwal UK, Abisambra JF, Zhang J, Dharia S, O'Leary JC, Patel T, Braswell K, Jani T, Gestwicki JE, Dickey CA

The three cornerstones of chemical biology: innovative probes, new discoveries, and enabling tools.

ACS chemical biology

Thompson AD, Makley LN, McMenimen K, Gestwicki JE

Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

PloS one

Koren J, Miyata Y, Kiray J, O'Leary JC, Nguyen L, Guo J, Blair LJ, Li X, Li X, Jinwal UK, Cheng JQ, Gestwicki JE, Dickey CA

Guidelines for the use and interpretation of assays for monitoring autophagy.

Autophagy

Klionsky DJ, Abdalla FC, Abeliovich H, Abraham RT, Acevedo-Arozena A, Adeli K, Agholme L, Agnello M, Agostinis P, Aguirre-Ghiso JA, Ahn HJ, Ait-Mohamed O, Ait-Si-Ali S, Akematsu T, Akira S, Al-Younes HM, Al-Zeer MA, Albert ML, Albin RL, Alegre-Abarrategui J, Aleo MF, Alirezaei M, Almasan A, Almonte-Becerril M, Amano A, Amaravadi R, Amarnath S, Amer AO, Andrieu-Abadie N, Anantharam V, Ann DK, Anoopkumar-Dukie S, Aoki H, Apostolova N, Arancia G, Aris JP, Asanuma K, Asare NY, Ashida H, Askanas V, Askew DS, Auberger P, Baba M, Backues SK, Baehrecke EH, Bahr BA, Bai XY, Bailly Y, Baiocchi R, Baldini G, Balduini W, Ballabio A, Bamber BA, Bampton ET, Bánhegyi G, Bartholomew CR, Bassham DC, Bast RC, Batoko H, Bay BH, Beau I, Béchet DM, Begley TJ, Behl C, Behrends C, Bekri S, Bellaire B, Bendall LJ, Benetti L, Berliocchi L, Bernardi H, Bernassola F, Besteiro S, Bhatia-Kissova I, Bi X, Biard-Piechaczyk M, Blum JS, Boise LH, Bonaldo P, Boone DL, Bornhauser BC, Bortoluci KR, Bossis I, Bost F, Bourquin JP, Boya P, Boyer-Guittaut M, Bozhkov PV, Brady NR, Brancolini C, Brech A, Brenman JE, Brennand A, Bresnick EH, Brest P, Bridges D, Bristol ML, Brookes PS, Brown EJ, Brumell JH, Brunetti-Pierri N, Brunk UT, Bulman DE, Bultman SJ, Bultynck G, Burbulla LF, Bursch W, Butchar JP, Buzgariu W, Bydlowski SP, Cadwell K, Cahová M, Cai D, Cai J, Cai Q, Calabretta B, Calvo-Garrido J, Camougrand N, Campanella M, Campos-Salinas J, Candi E, Cao L, Caplan AB, Carding SR, Cardoso SM, Carew JS, Carlin CR, Carmignac V, Carneiro LA, Carra S, Caruso RA, Casari G, Casas C, Castino R, Cebollero E, Cecconi F, Celli J, Chaachouay H, Chae HJ, Chai CY, Chan DC, Chan EY, Chang RC, Che CM, Chen CC, Chen GC, Chen GQ, Chen M, Chen Q, Chen SS, Chen W, Chen X, Chen X, Chen X, Chen YG, Chen Y, Chen Y, Chen YJ, Chen Z, Cheng A, Cheng CH, Cheng Y, Cheong H, Cheong JH, Cherry S, Chess-Williams R, Cheung ZH, Chevet E, Chiang HL, Chiarelli R, Chiba T, Chin LS, Chiou SH, Chisari FV, Cho CH, Cho DH, Choi AM, Choi D, Choi KS, Choi ME, Chouaib S, Choubey D, Choubey V, Chu CT, Chuang TH, Chueh SH, Chun T, Chwae YJ, Chye ML, Ciarcia R, Ciriolo MR, Clague MJ, Clark RS, Clarke PG, Clarke R, Codogno P, Coller HA, Colombo MI, Comincini S, Condello M, Condorelli F, Cookson MR, Coombs GH, Coppens I, Corbalan R, Cossart P, Costelli P, Costes S, Coto-Montes A, Couve E, Coxon FP, Cregg JM, Crespo JL, Cronjé MJ, Cuervo AM, Cullen JJ, Czaja MJ, D'Amelio M, Darfeuille-Michaud A, Davids LM, Davies FE, De Felici M, de Groot JF, de Haan CA, De Martino L, De Milito A, De Tata V, Debnath J, Degterev A, Dehay B, Delbridge LM, Demarchi F, Deng YZ, Dengjel J, Dent P, Denton D, Deretic V, Desai SD, Devenish RJ, Di Gioacchino M, Di Paolo G, Di Pietro C, Díaz-Araya G, Díaz-Laviada I, Diaz-Meco MT, Diaz-Nido J, Dikic I, Dinesh-Kumar SP, Ding WX, Distelhorst CW, Diwan A, Djavaheri-Mergny M, Dokudovskaya S, Dong Z, Dorsey FC, Dosenko V, Dowling JJ, Doxsey S, Dreux M, Drew ME, Duan Q, Duchosal MA, Duff K, Dugail I, Durbeej M, Duszenko M, Edelstein CL, Edinger AL, Egea G, Eichinger L, Eissa NT, Ekmekcioglu S, El-Deiry WS, Elazar Z, Elgendy M, Ellerby LM, Eng KE, Engelbrecht AM, Engelender S, Erenpreisa J, Escalante R, Esclatine A, Eskelinen EL, Espert L, Espina V, Fan H, Fan J, Fan QW, Fan Z, Fang S, Fang Y, Fanto M, Fanzani A, Farkas T, Farré JC, Faure M, Fechheimer M, Feng CG, Feng J, Feng Q, Feng Y, Fésüs L, Feuer R, Figueiredo-Pereira ME, Fimia GM, Fingar DC, Finkbeiner S, Finkel T, Finley KD, Fiorito F, Fisher EA, Fisher PB, Flajolet M, Florez-McClure ML, Florio S, Fon EA, Fornai F, Fortunato F, Fotedar R, Fowler DH, Fox HS, Franco R, Frankel LB, Fransen M, Fuentes JM, Fueyo J, Fujii J, Fujisaki K, Fujita E, Fukuda M, Furukawa RH, Gaestel M, Gailly P, Gajewska M, Galliot B, Galy V, Ganesh S, Ganetzky B, Ganley IG, Gao FB, Gao GF, Gao J, Garcia L, Garcia-Manero G, Garcia-Marcos M, Garmyn M, Gartel AL, Gatti E, Gautel M, Gawriluk TR, Gegg ME, Geng J, Germain M, Gestwicki JE, Gewirtz DA, Ghavami S, et al

Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo.

Autophagy

Congdon EE, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS, Gestwicki JE, Dickey CA, Yu WH, Duff KE

Protein quality control in neurodegenerative disease.

Progress in molecular biology and translational science

Gestwicki JE, Garza D

Ordered assembly of heat shock proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on expanded polyglutamine fragments revealed by chemical probes.

The Journal of biological chemistry

Walter GM, Smith MC, Wisén S, Basrur V, Elenitoba-Johnson KS, Duennwald ML, Kumar A, Gestwicki JE

Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies.

Future medicinal chemistry

Miyata Y, Koren J, Kiray J, Dickey CA, Gestwicki JE

Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP.

Molecular cell

Scaglione KM, Zavodszky E, Todi SV, Patury S, Xu P, Rodríguez-Lebrón E, Fischer S, Konen J, Djarmati A, Peng J, Gestwicki JE, Paulson HL

Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones.

Journal of molecular biology

Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, Zuiderweg ER

Insight into amyloid structure using chemical probes.

Chemical biology & drug design

Reinke AA, Gestwicki JE

Improved synthesis of 15-deoxyspergualin analogs using the Ugi multi-component reaction.

Bioorganic & medicinal chemistry letters

Evans CG, Smith MC, Carolan JP, Gestwicki JE

Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism.

Chemistry & biology

Chang L, Miyata Y, Ung PM, Bertelsen EB, McQuade TJ, Carlson HA, Zuiderweg ER, Gestwicki JE

Chemical probes that selectively recognize the earliest Aß oligomers in complex mixtures.

Journal of the American Chemical Society

Reinke AA, Ung PM, Quintero JJ, Carlson HA, Gestwicki JE

Identification of dihydropyridines that reduce cellular tau levels.

Chemical communications (Cambridge, England)

Evans CG, Jinwal UK, Makley LN, Dickey CA, Gestwicki JE

Bicinchoninic acid (BCA) assay in low volume.

Analytical biochemistry

Bainor A, Chang L, McQuade TJ, Webb B, Gestwicki JE

Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden.

Molecular neurodegeneration

O'Leary JC, Li Q, Marinec P, Blair LJ, Congdon EE, Johnson AG, Jinwal UK, Koren J, Jones JR, Kraft C, Peters M, Abisambra JF, Duff KE, Weeber EJ, Gestwicki JE, Dickey CA

High-throughput screen for Escherichia coli heat shock protein 70 (Hsp70/DnaK): ATPase assay in low volume by exploiting energy transfer.

Journal of biomolecular screening

Miyata Y, Chang L, Bainor A, McQuade TJ, Walczak CP, Zhang Y, Larsen MJ, Kirchhoff P, Gestwicki JE

Quantifying prefibrillar amyloids in vitro by using a "thioflavin-like" spectroscopic method.

Chembiochem : a European journal of chemical biology

Reinke AA, Abulwerdi GA, Gestwicki JE

Heat shock protein 70 (hsp70) as an emerging drug target.

Journal of medicinal chemistry

Evans CG, Chang L, Gestwicki JE

Binding of a small molecule at a protein-protein interface regulates the chaperone activity of hsp70-hsp40.

ACS chemical biology

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

Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation.

The Journal of biological chemistry

Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP

Hsc70 rapidly engages tau after microtubule destabilization.

The Journal of biological chemistry

Jinwal UK, O'Leary JC, Borysov SI, Jones JR, Li Q, Koren J, Abisambra JF, Vestal GD, Lawson LY, Johnson AG, Blair LJ, Jin Y, Miyata Y, Gestwicki JE, Dickey CA

Facilitating Akt clearance via manipulation of Hsp70 activity and levels.

The Journal of biological chemistry

Koren J, Jinwal UK, Jin Y, O'Leary J, Jones JR, Johnson AG, Blair LJ, Abisambra JF, Chang L, Miyata Y, Cheng AM, Guo J, Cheng JQ, Gestwicki JE, Dickey CA

Chemical manipulation of hsp70 ATPase activity regulates tau stability.

The Journal of neuroscience : the official journal of the Society for Neuroscience

Jinwal UK, Miyata Y, Koren J, Jones JR, Trotter JH, Chang L, O'Leary J, Morgan D, Lee DC, Shults CL, Rousaki A, Weeber EJ, Zuiderweg ER, Gestwicki JE, Dickey CA

Synthesis of orthogonally reactive FK506 derivatives via olefin cross metathesis.

Bioorganic & medicinal chemistry

Marinec PS, Evans CG, Gibbons GS, Tarnowski MA, Overbeek DL, Gestwicki JE

Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate.

Proceedings of the National Academy of Sciences of the United States of America

Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ER

FK506-binding protein (FKBP) partitions a modified HIV protease inhibitor into blood cells and prolongs its lifetime in vivo.

Proceedings of the National Academy of Sciences of the United States of America

Marinec PS, Chen L, Barr KJ, Mutz MW, Crabtree GR, Gestwicki JE

Conditional nuclear import and export of yeast proteins using a chemical inducer of dimerization.

Cell biochemistry and biophysics

Patury S, Geda P, Dobry CJ, Kumar A, Gestwicki JE

Pharmacological targeting of the Hsp70 chaperone.

Current topics in medicinal chemistry

Patury S, Miyata Y, Gestwicki JE

A poke in the eye: inhibiting HIV-1 protease through its flap-recognition pocket.

Biopolymers

Damm KL, Ung PM, Quintero JJ, Gestwicki JE, Carlson HA

A small molecule-directed approach to control protein localization and function.

Yeast (Chichester, England)

Geda P, Patury S, Ma J, Bharucha N, Dobry CJ, Lawson SK, Gestwicki JE, Kumar A

Chemical modulators of heat shock protein 70 (Hsp70) by sequential, microwave-accelerated reactions on solid phase.

Bioorganic & medicinal chemistry letters

Wisén S, Androsavich J, Evans CG, Chang L, Gestwicki JE

Derrubone, an inhibitor of the Hsp90 protein folding machinery.

Journal of natural products

Hadden MK, Galam L, Gestwicki JE, Matts RL, Blagg BS

Chemical control over protein-protein interactions: beyond inhibitors.

Combinatorial chemistry & high throughput screening

Gestwicki JE, Marinec PS

High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK.

Analytical biochemistry

Chang L, Bertelsen EB, Wisén S, Larsen EM, Zuiderweg ER, Gestwicki JE

Rescue of degradation-prone mutants of the FK506-rapamycin binding (FRB) protein with chemical ligands.

Chembiochem : a European journal of chemical biology

Stankunas K, Bayle JH, Havranek JJ, Wandless TJ, Baker D, Crabtree GR, Gestwicki JE

Potential therapeutic applications of autophagy.

Nature reviews. Drug discovery

Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ

Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro.

The Journal of biological chemistry

Evans CG, Wisén S, Gestwicki JE

Synthetic multivalent ligands as probes of signal transduction.

Angewandte Chemie (International ed. in English)

Kiessling LL, Gestwicki JE, Strong LE

Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity.

Chemistry & biology

Bayle JH, Grimley JS, Stankunas K, Gestwicki JE, Wandless TJ, Crabtree GR

'Nature-inspired' drug-protein complexes as inhibitors of Abeta aggregation.

Biochemical Society transactions

Bose M, Gestwicki JE, Devasthali V, Crabtree GR, Graef IA

Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation.

Science (New York, N.Y.)

Gestwicki JE, Crabtree GR, Graef IA

A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis.

Cell

Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Stankunas K, Graef IA, Crabtree GR

Conditional protein alleles using knockin mice and a chemical inducer of dimerization.

Molecular cell

Stankunas K, Bayle JH, Gestwicki JE, Lin YM, Wandless TJ, Crabtree GR

Visualization and characterization of receptor clusters by transmission electron microscopy.

Methods in enzymology

Gestwicki JE, Cairo CW, Borrok MJ, Kiessling LL

Influencing receptor-ligand binding mechanisms with multivalent ligand architecture.

Journal of the American Chemical Society

Gestwicki JE, Cairo CW, Strong LE, Oetjen KA, Kiessling LL

Conserved amplification of chemotactic responses through chemoreceptor interactions.

Journal of bacteriology

Lamanna AC, Gestwicki JE, Strong LE, Borchardt SL, Owen RM, Kiessling LL

Synthesis and applications of end-labeled neoglycopolymers.

Organic letters

Owen RM, Gestwicki JE, Young T, Kiessling LL

Selective immobilization of multivalent ligands for surface plasmon resonance and fluorescence microscopy.

Analytical biochemistry

Gestwicki JE, Cairo CW, Mann DA, Owen RM, Kiessling LL

Control of multivalent interactions by binding epitope density.

Journal of the American Chemical Society

Cairo CW, Gestwicki JE, Kanai M, Kiessling LL

Cell aggregation by scaffolded receptor clusters.

Chemistry & biology

Gestwicki JE, Strong LE, Cairo CW, Boehm FJ, Kiessling LL

Designed potent multivalent chemoattractants for Escherichia coli.

Bioorganic & medicinal chemistry

Gestwicki JE, Strong LE, Borchardt SL, Cairo CW, Schnoes AM, Kiessling LL

Synthetic multivalent ligands in the exploration of cell-surface interactions.

Current opinion in chemical biology

Kiessling LL, Gestwicki JE, Strong LE

Evolutionary conservation of methyl-accepting chemotaxis protein location in Bacteria and Archaea.

Journal of bacteriology

Gestwicki JE, Lamanna AC, Harshey RM, McCarter LL, Kiessling LL, Adler J

A quantitative-trait locus controlling peripheral B-cell deficiency maps to mouse Chromosome 15.

Immunogenetics

Hoag KA, Clise-Dwyer K, Lim YH, Nashold FE, Gestwicki J, Cancro MP, Hayes CE

Motility and chemotaxis of filamentous cells of Escherichia coli.

Journal of bacteriology

Maki N, Gestwicki JE, Lake EM, Kiessling LL, Adler J

Tuning chemotactic responses with synthetic multivalent ligands.

Chemistry & biology

Gestwicki JE, Strong LE, Kiessling LL

Microwave-induced esterification using heterogeneous acid catalyst in a low dielectric constant medium

The Journal of organic chemistry

Kabza KG, Chapados BR, Gestwicki JE, McGrath JL

Synthesis of end-labeled multivalent ligands for exploring cell-surface-receptor-ligand interactions.

Chemistry & biology

Gordon EJ, Gestwicki JE, Strong LE, Kiessling LL