Jason Gestwicki, PhD

Professor
Executive Committee Member
Department of Pharmaceutical Chemistry
[email protected]
Phone: +1 415 502-7121
Fax: +1 415 502-7053
675 Nelson Rising Lane, Rm 311
UCSF Box 0518
San Francisco, CA 94158
United States

Links

The Gestwicki Lab UCSF Profiles

Affiliations

Education programs

Director, Quantitative Biosciences Consortium (QBC)
Director, Chemistry and Chemical Biology Graduate Program (CCB)

What I do

My research group studies how molecular chaperones maintain protein homeostasis. This question is important because imbalances in protein homeostasis are linked to a number of incurable diseases, including neurodegenerative disorders. Molecular chaperones regulate all aspects of a protein’s lifecycle, including its expression, folding, trafficking and degradation. However, it isn’t yet clear how we might promote the activity of chaperones to cure diseases. Our approach to this question is to develop chemical probes that reveal how chaperones interact with disease-associated proteins.

Departmental research area

chemical biology and medicinal chemistry

My research expertise

protein homeostasis, molecular chaperones, Alzheimer's disease, protein-protein interaction (PPI), high-throughput screening (HTS), Drug Discovery

Professional background

Degrees

PhD, University of Wisconsin Madison, 2002
BS, State University of New York Fredonia, 1997

Biography

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.

Research keywords

  • protein misfolding diseases
  • protein-protein interactions
  • medicinal chemistry
  • protein folding
  • high throughput screening
  • molecular chaperones
  • organic synthesis
  • allostery
  • Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • molecular chaperones
  • Protein Binding
  • tau Proteins
  • Escherichia coli Proteins
  • HSP70 Heat-Shock Proteins
  • protein folding
  • Benzothiazoles
  • Protein Interaction Maps
  • HSP40 Heat-Shock Proteins
  • Apoptosis Regulatory Proteins
  • HSC70 Heat-Shock Proteins
  • Tauopathies
  • Proteostasis
1. UCSF QBI Coronavirus Research Group awarded $67.5 million to develop therapies for future pandemics
2. 2020 Mary Anne Koda-Kimble Seed Award for Innovation fuels vital research across the School
3. Update from the Dean – November 2019
4. Two School members earn UCSF Chancellor’s Awards for Diversity
5. School scientists identify faulty molecular recycling as potential driver of Alzheimer’s disease
6. Celebrating the 100th birthday of Edward Leong Way
7. Study identifies eye-drop-soluble compound that could treat cataracts
8. Update from the Dean - Fall 2013
1. Everson Lecture, University of Wisconsin-Madison, 2020
2. Chair, Bioorganic Chemistry GRC, 2019
3. Dean’s Apple Award, Outstanding Teaching in UCSF School of Pharmacy, 2018
4. Elected Fellow, Cell Stress Society International (CSSI), 2018
5. Keynote Speaker, 9th International Symposium on Heat Shock Proteins in Biology and Medicine, 2018
6. Director, Chemistry & Chemical Biology Ph.D. Program, University of California San Francisco, 2017
7. Plenary Lecture, Midwest Stress Response Meeting, 2013
8. American Association for the Advancement of Science (AAAS) Fellow, 2012
9. Co-Chair, Keystone Meeting “Chemical Biology and Novel Probes in Pharmacology”, 2012
10. William B. Pratt Collegiate Professorship, University of Michigan, 2011-2013
11. Everson Lecturer, University of Wisconsin-Madison, 2010
12. NSF CAREER Award, 2009
13. McKnight Foundation's Brain Disorders Award, 2006
14. Biological Sciences Scholar, University of Michigan, 2005
15. Helen Hay Whitney Foundation Fellow, Stanford University, 2003
16. Sigrid Leirmo Award, University of Wisconsin - Madison, 2001
17. NIH Biotechnology Training Fellow, University of Wisconsin - Madison, 1998

Publications

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. Plexin D1 emerges as a novel target in the development of neural lineage plasticity in treatment-resistant prostate cancer. Res Sq. 2024 Mar 27.
Ahmad T, Alhammadi BA, Almaazmi SY, Arafa S, Blatch GL, Dutta T, Gestwicki JE, Keyzers RA, Shonhai A, Singh H. Plasmodium falciparum heat shock proteins as anti-malarial drug targets: An update. Cell Stress Chaperones. 2024 Mar 20.
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. A missense mutation in the Hspa8 gene encoding heat shock cognate protein 70 causes neuroaxonal dystrophy in rats. Front Neurosci. 2024; 18:1263724.
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. Stress biology: Complexity and multifariousness in health and disease. Cell Stress Chaperones. 2024 Feb; 29(1):143-157.
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. J-domain proteins: From molecular mechanisms to diseases. Cell Stress Chaperones. 2024 Feb; 29(1):21-33.
Lam M, Kuo SY, Reis S, Gestwicki JE, Silva MC, Haggarty SJ. Cholesterol Dysregulation Drives Seed-Dependent Tau Aggregation in Patient Stem Cell-Derived Models of Tauopathy. bioRxiv. 2023 Dec 12.
Wu T, Hornsby M, Zhu L, Yu JC, Shokat KM, Gestwicki JE. Protocol for performing and optimizing differential scanning fluorimetry experiments. STAR Protoc. 2023 Dec 15; 4(4):102688.
Zhang JZ, Greenwood N, Hernandez J, Cuperus JT, Huang B, Ryder BD, Queitsch C, Gestwicki JE, Baker D. De novo designed Hsp70 activator dissolves intracellular condensates. bioRxiv. 2023 Sep 19.
Nadel CM, Wucherer K, Oehler A, Thwin AC, Basu K, Callahan MD, Southworth DR, Mordes DA, Craik CS, Gestwicki JE. Phosphorylation of a Cleaved Tau Proteoform at a Single Residue Inhibits Binding to the E3 Ubiquitin Ligase, CHIP. bioRxiv. 2023 Aug 16.
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. An Unbiased Screen Identified the Hsp70-BAG3 Complex as a Regulator of Myosin-Binding Protein C3. JACC Basic Transl Sci. 2023 Sep; 8(9):1198-1211.
Nadel CM, Thwin AC, Callahan M, Lee K, Connelly E, Craik CS, Southworth DR, Gestwicki JE. The E3 Ubiquitin Ligase, CHIP/STUB1, Inhibits Aggregation of Phosphorylated Proteoforms of Microtubule-associated Protein Tau (MAPT). J Mol Biol. 2023 06 01; 435(11):168026.
Braxton JR, Shao H, Tse E, Gestwicki JE, Southworth DR. Asymmetric apical domain states of mitochondrial Hsp60 coordinate substrate engagement and chaperonin assembly. bioRxiv. 2023 May 15.
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. Mitoribosome sensitivity to HSP70 inhibition uncovers metabolic liabilities of castration-resistant prostate cancer. PNAS Nexus. 2023 Apr; 2(4):pgad115.
Elsasser S, Elia LP, Morimoto RI, Powers ET, Finley D, Costa B, Budron M, Tokuno Z, Wang S, Iyer RG, Barth B, Mockler E, Finkbeiner S, Gestwicki JE, Richardson RAK, Stoeger T, Tan EP, Xiao Q, Cole CM, Massey LA, Garza D, Kelly JW, Rainbolt TK, Chou CC, Masto VB, Frydman J, Nixon RA. A Comprehensive Enumeration of the Human Proteostasis Network. 2. Components of the Autophagy-Lysosome Pathway. bioRxiv. 2023 Mar 24.
Xu P, Yang JC, Ning S, Chen B, Nip C, Wei Q, Liu L, Johnson OT, Gao AC, Gestwicki JE, Evans CP, Liu C. Allosteric inhibition of HSP70 in collaboration with STUB1 augments enzalutamide efficacy in antiandrogen resistant prostate tumor and patient-derived models. Pharmacol Res. 2023 03; 189:106692.
Montgomery KM, Carroll EC, Thwin AC, Quddus AY, Hodges P, Southworth DR, Gestwicki JE. Chemical Features of Polyanions Modulate Tau Aggregation and Conformational States. J Am Chem Soc. 2023 Feb 08.
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. Conformationally responsive dyes enable protein-adaptive differential scanning fluorimetry. bioRxiv. 2023 Jan 28.
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. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 macrodomain of SARS-CoV-2. Proc Natl Acad Sci U S A. 2023 01 10; 120(2):e2212931120.
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. N-myc-Mediated Translation Control Is a Therapeutic Vulnerability in Medulloblastoma. Cancer Res. 2023 01 04; 83(1):130-140.
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. Iterative computational design and crystallographic screening identifies potent inhibitors targeting the Nsp3 Macrodomain of SARS-CoV-2. bioRxiv. 2022 Jul 28.
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. Allosteric HSP70 inhibitors perturb mitochondrial proteostasis and overcome proteasome inhibitor resistance in multiple myeloma. Cell Chem Biol. 2022 08 18; 29(8):1288-1302.e7.
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. A campaign targeting a conserved Hsp70 binding site uncovers how subcellular localization is linked to distinct biological activities. Cell Chem Biol. 2022 08 18; 29(8):1303-1316.e3.
Johnson OT, Gestwicki JE. Multivalent protein-protein interactions are pivotal regulators of eukaryotic Hsp70 complexes. Cell Stress Chaperones. 2022 07; 27(4):397-415.
Carrettiero DC, Almeida MC, Longhini AP, Rauch JN, Han D, Zhang X, Najafi S, Gestwicki JE, Kosik KS. Stress routes clients to the proteasome via a BAG2 ubiquitin-independent degradation condensate. Nat Commun. 2022 06 02; 13(1):3074.
Gestwicki JE. Multi-protein complexes as drug targets. Cell Chem Biol. 2022 05 19; 29(5):713-715.
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. Microglial NF-κB drives tau spreading and toxicity in a mouse model of tauopathy. Nat Commun. 2022 04 12; 13(1):1969.
Opoku-Nsiah KA, de la Pena AH, Williams SK, Chopra N, Sali A, Lander GC, Gestwicki JE. The YΦ motif defines the structure-activity relationships of human 20S proteasome activators. Nat Commun. 2022 03 09; 13(1):1226.
Johnson OT, Nadel CM, Carroll EC, Arhar T, Gestwicki JE. Two distinct classes of cochaperones compete for the EEVD motif in heat shock protein 70 to tune its chaperone activities. J Biol Chem. 2022 03; 298(3):101697.
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. Selective vulnerabilities in the proteostasis network of castration-resistant prostate cancer. Cell Chem Biol. 2022 03 17; 29(3):490-501.e4.
Hong SK, Starenki D, Johnson OT, Gestwicki JE, Park JI. Analogs of the Heat Shock Protein 70 Inhibitor MKT-077 Suppress Medullary Thyroid Carcinoma Cells. Int J Mol Sci. 2022 Jan 19; 23(3).
Arhar T, Shkedi A, Nadel CM, Gestwicki JE. The interactions of molecular chaperones with client proteins: why are they so weak? J Biol Chem. 2021 11; 297(5):101282.
Shkedi A, Adkisson M, Schroeder A, Eckalbar WL, Kuo SY, Neckers L, Gestwicki JE. Inhibitor Combinations Reveal Wiring of the Proteostasis Network in Prostate Cancer Cells. J Med Chem. 2021 10 14; 64(19):14809-14821.
Lee K, Thwin AC, Nadel CM, Tse E, Gates SN, Gestwicki JE, Southworth DR. The structure of an Hsp90-immunophilin complex reveals cochaperone recognition of the client maturation state. Mol Cell. 2021 09 02; 81(17):3496-3508.e5.
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. Adhesion-mediated mechanosignaling forces mitohormesis. Cell Metab. 2021 07 06; 33(7):1322-1341.e13.
Evans CG, Gestwicki JE. Retraction of "Enantioselective Organocatalytic Hantzsch Synthesis of Polyhydroquinolines". Org Lett. 2021 May 07; 23(9):3802.
Caballero B, Bourdenx M, Luengo E, Diaz A, Sohn PD, Chen X, Wang C, Juste YR, Wegmann S, Patel B, Young ZT, Kuo SY, Rodriguez-Navarro JA, Shao H, Lopez MG, Karch CM, Goate AM, Gestwicki JE, Hyman BT, Gan L, Cuervo AM. Acetylated tau inhibits chaperone-mediated autophagy and promotes tau pathology propagation in mice. Nat Commun. 2021 04 14; 12(1):2238.
Schuller M, Correy GJ, Gahbauer S, Fearon D, Wu T, Díaz RE, Young ID, Carvalho Martins L, Smith DH, Schulze-Gahmen U, Owens TW, Deshpande I, Merz GE, Thwin AC, Biel JT, Peters JK, Moritz M, Herrera N, Kratochvil HT, QCRG Structural Biology Consortium, Aimon A, Bennett JM, Brandao Neto J, Cohen AE, Dias A, Douangamath A, Dunnett L, Fedorov O, Ferla MP, Fuchs MR, 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, O'Brien P, Jura N, Ashworth A, Irwin JJ, Thompson MC, Gestwicki JE, von Delft F, Shoichet BK, Fraser JS, Ahel I. Fragment binding to the Nsp3 macrodomain of SARS-CoV-2 identified through crystallographic screening and computational docking. Sci Adv. 2021 04; 7(16).
Shao H, Li X, Hayashi S, Bertron JL, Schwarz DMC, Tang BC, Gestwicki JE. Inhibitors of heat shock protein 70 (Hsp70) with enhanced metabolic stability reduce tau levels. Bioorg Med Chem Lett. 2021 06 01; 41:128025.
Tao J, Berthet A, Citron YR, Tsiolaki PL, Stanley R, Gestwicki JE, Agard DA, McConlogue L. Hsp70 chaperone blocks α-synuclein oligomer formation via a novel engagement mechanism. J Biol Chem. 2021 Jan-Jun; 296:100613.
Abrams J, Arhar T, Mok SA, Taylor IR, Kampmann M, Gestwicki JE. Functional genomics screen identifies proteostasis targets that modulate prion protein (PrP) stability. Cell Stress Chaperones. 2021 03; 26(2):443-452.
Makley LN, Johnson OT, Ghanakota P, Rauch JN, Osborn D, Wu TS, Cierpicki T, Carlson HA, Gestwicki JE. Chemical validation of a druggable site on Hsp27/HSPB1 using in silico solvent mapping and biophysical methods. Bioorg Med Chem. 2021 03 15; 34:115990.
Dutta T, Singh H, Gestwicki JE, Blatch GL. Exported plasmodial J domain protein, PFE0055c, and PfHsp70-x form a specific co-chaperone-chaperone partnership. Cell Stress Chaperones. 2021 03; 26(2):355-366.
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, QCRG Structural Biology Consortium, 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, Johannes Gregor Matthias Rack, 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. Fragment Binding to the Nsp3 Macrodomain of SARS-CoV-2 Identified Through Crystallographic Screening and Computational Docking. bioRxiv. 2020 Nov 24.
Nadel CM, Ran X, Gestwicki JE. Luminescence complementation assay for measurement of binding to protein C-termini in live cells. Anal Biochem. 2020 12 15; 611:113947.
Schwarz DMC, Williams SK, Dillenburg M, Wagner CR, Gestwicki JE. A Phosphoramidate Strategy Enables Membrane Permeability of a Non-nucleotide Inhibitor of the Prolyl Isomerase Pin1. ACS Med Chem Lett. 2020 Sep 10; 11(9):1704-1710.
Bengoechea R, Findlay AR, Bhadra AK, Shao H, Stein KC, Pittman SK, Daw JA, Gestwicki JE, True HL, Weihl CC. Inhibition of DNAJ-HSP70 interaction improves strength in muscular dystrophy. J Clin Invest. 2020 08 03; 130(8):4470-4485.
Shao H, Oltion K, Wu T, Gestwicki JE. Differential scanning fluorimetry (DSF) screen to identify inhibitors of Hsp60 protein-protein interactions. Org Biomol Chem. 2020 06 10; 18(22):4157-4163.
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. A Novel Radioligand Reveals Tissue Specific Pharmacological Modulation of Glucocorticoid Receptor Expression with Positron Emission Tomography. ACS Chem Biol. 2020 06 19; 15(6):1381-1391.
Wu PK, Hong SK, Starenki D, Oshima K, Shao H, Gestwicki JE, Tsai S, Park JI. Mortalin/HSPA9 targeting selectively induces KRAS tumor cell death by perturbing mitochondrial membrane permeability. Oncogene. 2020 05; 39(21):4257-4270.
Jackson JW, Rivera-Marquez GM, Beebe K, Tran AD, Trepel JB, Gestwicki JE, Blagg BSJ, Ohkubo S, Neckers LM. Pharmacologic dissection of the overlapping impact of heat shock protein family members on platelet function. J Thromb Haemost. 2020 05; 18(5):1197-1209.
Wu PK, Hong SK, Chen W, Becker AE, Gundry RL, Lin CW, Shao H, Gestwicki JE, Park JI. Mortalin (HSPA9) facilitates BRAF-mutant tumor cell survival by suppressing ANT3-mediated mitochondrial membrane permeability. Sci Signal. 2020 03 10; 13(622).
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. Management of Hsp90-Dependent Protein Folding by Small Molecules Targeting the Aha1 Co-Chaperone. Cell Chem Biol. 2020 03 19; 27(3):292-305.e6.
Shao H, Gestwicki JE. Neutral analogs of the heat shock protein 70 (Hsp70) inhibitor, JG-98. Bioorg Med Chem Lett. 2020 03 01; 30(5):126954.
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. Tryptophan scanning mutagenesis as a way to mimic the compound-bound state and probe the selectivity of allosteric inhibitors in cells. Chem Sci. 2020 Jan 10; 11(7):1892-1904.
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. Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy. Mol Neurodegener. 2020 01 06; 15(1):2.
Wang C, Scott SM, Sun S, Zhao P, Hutt DM, Shao H, Gestwicki JE, Balch WE. Individualized management of genetic diversity in Niemann-Pick C1 through modulation of the Hsp70 chaperone system. Hum Mol Genet. 2020 01 01; 29(1):1-19.
Ravalin M, Basu K, Gestwicki JE, Craik CS. End-Binding E3 Ubiquitin Ligases Enable Protease Signaling. ACS Chem Biol. 2021 11 19; 16(11):2047-2056.
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. Author Correction: Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor. Nat Commun. 2019 Oct 07; 10(1):4605.
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. Compromised function of the ESCRT pathway promotes endolysosomal escape of tau seeds and propagation of tau aggregation. J Biol Chem. 2019 12 13; 294(50):18952-18966.
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. Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis. Neuron. 2019 11 06; 104(3):458-470.e5.
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. Hsp70 and Hsp40 inhibit an inter-domain interaction necessary for transcriptional activity in the androgen receptor. Nat Commun. 2019 08 08; 10(1):3562.
Molnar KS, Dunyak BM, Su B, Izrayelit Y, McGlasson-Naumann B, Hamilton PD, Qian M, Covey DF, Gestwicki JE, Makley LN, Andley UP. Mechanism of Action of VP1-001 in cryAB(R120G)-Associated and Age-Related Cataracts. Invest Ophthalmol Vis Sci. 2019 08 01; 60(10):3320-3331.
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. Specificity for latent C termini links the E3 ubiquitin ligase CHIP to caspases. Nat Chem Biol. 2019 08; 15(8):786-794.
Lee E, Ouzounova M, Piranlioglu R, Ma MT, Guzel M, Marasco D, Chadli A, Gestwicki JE, Cowell JK, Wicha MS, Hassan KA, Korkaya H. Correction: The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20. Oncogene. 2019 Jul; 38(28):5749.
Moss SM, Taylor IR, Ruggero D, Gestwicki JE, Shokat KM, Mukherjee S. A Legionella pneumophila Kinase Phosphorylates the Hsp70 Chaperone Family to Inhibit Eukaryotic Protein Synthesis. Cell Host Microbe. 2019 03 13; 25(3):454-462.e6.
Taguwa S, Yeh MT, Rainbolt TK, Nayak A, Shao H, Gestwicki JE, Andino R, Frydman J. Zika Virus Dependence on Host Hsp70 Provides a Protective Strategy against Infection and Disease. Cell Rep. 2019 01 22; 26(4):906-920.e3.
Zaiter SS, Huo Y, Tiew FY, Gestwicki JE, McAlpine SR. Designing de Novo Small Molecules That Control Heat Shock Protein 70 (Hsp70) and Heat Shock Organizing Protein (HOP) within the Chaperone Protein-Folding Machinery. J Med Chem. 2019 01 24; 62(2):742-761.
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. Myopathy associated BAG3 mutations lead to protein aggregation by stalling Hsp70 networks. Nat Commun. 2018 12 17; 9(1):5342.
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. Predicting protein targets for drug-like compounds using transcriptomics. PLoS Comput Biol. 2018 12; 14(12):e1006651.
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. Function, evolution, and structure of J-domain proteins. Cell Stress Chaperones. 2019 01; 24(1):7-15.
Rinaldi S, Assimon VA, Young ZT, Morra G, Shao H, Taylor IR, Gestwicki JE, Colombo G. A Local Allosteric Network in Heat Shock Protein 70 (Hsp70) Links Inhibitor Binding to Enzyme Activity and Distal Protein-Protein Interactions. ACS Chem Biol. 2018 11 16; 13(11):3142-3152.
Freilich R, Betegon M, Tse E, Mok SA, Julien O, Agard DA, Southworth DR, Takeuchi K, Gestwicki JE. Competing protein-protein interactions regulate binding of Hsp27 to its client protein tau. Nat Commun. 2018 11 01; 9(1):4563.
Gestwicki JE, Shao H. Inhibitors and chemical probes for molecular chaperone networks. J Biol Chem. 2019 02 08; 294(6):2151-2161.
Lee E, Ouzounova M, Piranlioglu R, Ma MT, Guzel M, Marasco D, Chadli A, Gestwicki JE, Cowell JK, Wicha MS, Hassan KA, Korkaya H. The pleiotropic effects of TNFα in breast cancer subtypes is regulated by TNFAIP3/A20. Oncogene. 2019 01; 38(4):469-482.
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. KHS101 disrupts energy metabolism in human glioblastoma cells and reduces tumor growth in mice. Sci Transl Med. 2018 08 15; 10(454).
Shao H, Li X, Moses MA, Gilbert LA, Kalyanaraman C, Young ZT, Chernova M, Journey SN, Weissman JS, Hann B, Jacobson MP, Neckers L, Gestwicki JE. Exploration of Benzothiazole Rhodacyanines as Allosteric Inhibitors of Protein-Protein Interactions with Heat Shock Protein 70 (Hsp70). J Med Chem. 2018 Jul 26; 61(14):6163-6177.
Opoku-Nsiah KA, Gestwicki JE. Aim for the core: suitability of the ubiquitin-independent 20S proteasome as a drug target in neurodegeneration. Transl Res. 2018 08; 198:48-57.
Ran X, Gestwicki JE. Inhibitors of protein-protein interactions (PPIs): an analysis of scaffold choices and buried surface area. Curr Opin Chem Biol. 2018 06; 44:75-86.
Glazier AA, Hafeez N, Mellacheruvu D, Basrur V, Nesvizhskii AI, Lee LM, Shao H, Tang V, Yob JM, Gestwicki JE, Helms AS, Day SM. HSC70 is a chaperone for wild-type and mutant cardiac myosin binding protein C. JCI Insight. 2018 06 07; 3(11).
Schwarz DMC, Gestwicki JE. Revisiting the "Art of the Chemical Probe". ACS Chem Biol. 2018 05 18; 13(5):1109-1110.
Moses MA, Kim YS, Rivera-Marquez GM, Oshima N, Watson MJ, Beebe KE, Wells C, Lee S, Zuehlke AD, Shao H, Bingman WE, Kumar V, Malhotra SV, Weigel NL, Gestwicki JE, Trepel JB, Neckers LM. Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2018 07 15; 78(14):4022-4035.
Taylor IR, Ahmad A, Wu T, Nordhues BA, Bhullar A, Gestwicki JE, Zuiderweg ERP. The disorderly conduct of Hsc70 and its interaction with the Alzheimer's-related Tau protein. J Biol Chem. 2018 07 06; 293(27):10796-10809.
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. Mapping interactions with the chaperone network reveals factors that protect against tau aggregation. Nat Struct Mol Biol. 2018 05; 25(5):384-393.
Ouimet CM, Dawod M, Grinias J, Assimon VA, Lodge J, Mapp AK, Gestwicki JE, Kennedy RT. Protein cross-linking capillary electrophoresis at increased throughput for a range of protein-protein interactions. Analyst. 2018 Apr 16; 143(8):1805-1812.
Ran X, Burchfiel ET, Dong B, Rettko NJ, Dunyak BM, Shao H, Thiele DJ, Gestwicki JE. Rational design and screening of peptide-based inhibitors of heat shock factor 1 (HSF1). Bioorg Med Chem. 2018 10 15; 26(19):5299-5306.
Freilich R, Arhar T, Abrams JL, Gestwicki JE. Protein-Protein Interactions in the Molecular Chaperone Network. Acc Chem Res. 2018 04 17; 51(4):940-949.
Min SW, Sohn PD, Li Y, Devidze N, Johnson JR, Krogan NJ, Masliah E, Mok SA, Gestwicki JE, Gan L. SIRT1 Deacetylates Tau and Reduces Pathogenic Tau Spread in a Mouse Model of Tauopathy. J Neurosci. 2018 04 11; 38(15):3680-3688.
Taylor IR, Dunyak BM, Komiyama T, Shao H, Ran X, Assimon VA, Kalyanaraman C, Rauch JN, Jacobson MP, Zuiderweg ERP, Gestwicki JE. High-throughput screen for inhibitors of protein-protein interactions in a reconstituted heat shock protein 70 (Hsp70) complex. J Biol Chem. 2018 03 16; 293(11):4014-4025.
Young ZT, Mok SA, Gestwicki JE. Therapeutic Strategies for Restoring Tau Homeostasis. Cold Spring Harb Perspect Med. 2018 01 02; 8(1).
Cesa LC, Shao H, Srinivasan SR, Tse E, Jain C, Zuiderweg ERP, Southworth DR, Mapp AK, Gestwicki JE. X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition. J Biol Chem. 2018 02 16; 293(7):2370-2380.
Srinivasan SR, Cesa LC, Li X, Julien O, Zhuang M, Shao H, Chung J, Maillard I, Wells JA, Duckett CS, Gestwicki JE. Heat Shock Protein 70 (Hsp70) Suppresses RIP1-Dependent Apoptotic and Necroptotic Cascades. Mol Cancer Res. 2018 01; 16(1):58-68.
Rauch JN, Olson SH, Gestwicki JE. Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules. Cold Spring Harb Perspect Med. 2017 Jul 05; 7(7).
Pricer R, Gestwicki JE, Mapp AK. From Fuzzy to Function: The New Frontier of Protein-Protein Interactions. Acc Chem Res. 2017 03 21; 50(3):584-589.
Zuiderweg ER, Hightower LE, Gestwicki JE. The remarkable multivalency of the Hsp70 chaperones. Cell Stress Chaperones. 2017 03; 22(2):173-189.
Rauch JN, Tse E, Freilich R, Mok SA, Makley LN, Southworth DR, Gestwicki JE. BAG3 Is a Modular, Scaffolding Protein that physically Links Heat Shock Protein 70 (Hsp70) to the Small Heat Shock Proteins. J Mol Biol. 2017 01 06; 429(1):128-141.
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. Unbiased screen identifies aripiprazole as a modulator of abundance of the polyglutamine disease protein, ataxin-3. Brain. 2016 11 01; 139(11):2891-2908.
Zuiderweg ER, Gestwicki JE. Backbone and methyl resonance assignments of the 42 kDa human Hsc70 nucleotide binding domain in the ADP state. Biomol NMR Assign. 2017 04; 11(1):11-15.
Gabai VL, Yaglom JA, Wang Y, Meng L, Shao H, Kim G, Colvin T, Gestwicki J, Sherman MY. Anticancer Effects of Targeting Hsp70 in Tumor Stromal Cells. Cancer Res. 2016 10 15; 76(20):5926-5932.
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. Stabilizing the Hsp70-Tau Complex Promotes Turnover in Models of Tauopathy. Cell Chem Biol. 2016 08 18; 23(8):992-1001.
Rauch JN, Zuiderweg ER, Gestwicki JE. Non-canonical Interactions between Heat Shock Cognate Protein 70 (Hsc70) and Bcl2-associated Anthanogene (BAG) Co-Chaperones Are Important for Client Release. J Biol Chem. 2016 09 16; 291(38):19848-57.
Ouimet CM, Shao H, Rauch JN, Dawod M, Nordhues B, Dickey CA, Gestwicki JE, Kennedy RT. Protein Cross-Linking Capillary Electrophoresis for Protein-Protein Interaction Analysis. Anal Chem. 2016 08 16; 88(16):8272-8.
Dunyak BM, Gestwicki JE. Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds. J Med Chem. 2016 11 10; 59(21):9622-9644.
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 08 09; 113(32):9015-20.
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. Structural and Biological Interaction of hsc-70 Protein with Phosphatidylserine in Endosomal Microautophagy. J Biol Chem. 2016 08 26; 291(35):18096-106.
Martin MD, Baker JD, Suntharalingam A, Nordhues BA, Shelton LB, Zheng D, Sabbagh JJ, Haystead TA, Gestwicki JE, Dickey CA. Inhibition of Both Hsp70 Activity and Tau Aggregation in Vitro Best Predicts Tau Lowering Activity of Small Molecules. ACS Chem Biol. 2016 07 15; 11(7):2041-8.
Paatero AO, Kellosalo J, Dunyak BM, Almaliti J, Gestwicki JE, Gerwick WH, Taunton J, Paavilainen VO. Apratoxin Kills Cells by Direct Blockade of the Sec61 Protein Translocation Channel. Cell Chem Biol. 2016 05 19; 23(5):561-566.
Khachatoorian R, Riahi R, Ganapathy E, Shao H, Wheatley NM, Sundberg C, Jung CL, Ruchala P, Dasgupta A, Arumugaswami V, Gestwicki JE, French SW. Allosteric heat shock protein 70 inhibitors block hepatitis C virus assembly. Int J Antimicrob Agents. 2016 Apr; 47(4):289-96.
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. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 2016; 12(1):1-222.
Li X, Shao H, Taylor IR, Gestwicki JE. Targeting Allosteric Control Mechanisms in Heat Shock Protein 70 (Hsp70). Curr Top Med Chem. 2016; 16(25):2729-40.
Assimon VA, Southworth DR, Gestwicki JE. Specific Binding of Tetratricopeptide Repeat Proteins to Heat Shock Protein 70 (Hsp70) and Heat Shock Protein 90 (Hsp90) Is Regulated by Affinity and Phosphorylation. Biochemistry. 2015 Dec 08; 54(48):7120-31.
Taguwa S, Maringer K, Li X, Bernal-Rubio D, Rauch JN, Gestwicki JE, Andino R, Fernandez-Sesma A, Frydman J. Defining Hsp70 Subnetworks in Dengue Virus Replication Reveals Key Vulnerability in Flavivirus Infection. Cell. 2015 Nov 19; 163(5):1108-1123.
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. Pharmacological chaperone for α-crystallin partially restores transparency in cataract models. Science. 2015 Nov 06; 350(6261):674-7.
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. Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits. Nat Med. 2015 Oct; 21(10):1154-62.
Dunyak BM, Nakamura RL, Frankel AD, Gestwicki JE. Selective Targeting of Cells via Bispecific Molecules That Exploit Coexpression of Two Intracellular Proteins. ACS Chem Biol. 2015 Nov 20; 10(11):2441-7.
Cesa LC, Mapp AK, Gestwicki JE. Direct and Propagated Effects of Small Molecules on Protein-Protein Interaction Networks. Front Bioeng Biotechnol. 2015; 3:119.
Guan S, Trnka MJ, Bushnell DA, Robinson PJ, Gestwicki JE, Burlingame AL. Deconvolution method for specific and nonspecific binding of ligand to multiprotein complex by native mass spectrometry. Anal Chem. 2015 Aug 18; 87(16):8541-6.
Fontaine SN, Martin MD, Akoury E, Assimon VA, Borysov S, Nordhues BA, Sabbagh JJ, Cockman M, Gestwicki JE, Zweckstetter M, Dickey CA. The active Hsc70/tau complex can be exploited to enhance tau turnover without damaging microtubule dynamics. Hum Mol Genet. 2015 Jul 15; 24(14):3971-81.
Fontaine SN, Rauch JN, Nordhues BA, Assimon VA, Stothert AR, Jinwal UK, Sabbagh JJ, Chang L, Stevens SM, Zuiderweg ER, Gestwicki JE, Dickey CA. Isoform-selective Genetic Inhibition of Constitutive Cytosolic Hsp70 Activity Promotes Client Tau Degradation Using an Altered Co-chaperone Complement. J Biol Chem. 2015 May 22; 290(21):13115-27.
Assimon VA, Shao H, Garneau-Tsodikova S, Gestwicki JE. Concise Synthesis of Spergualin-Inspired Molecules With Broad-Spectrum Antibiotic Activity. Medchemcomm. 2015 May 01; 6(5):912-918.
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. Synthesis, stereochemical analysis, and derivatization of myricanol provide new probes that promote autophagic tau clearance. ACS Chem Biol. 2015 Apr 17; 10(4):1099-109.
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. Validation of the Hsp70-Bag3 protein-protein interaction as a potential therapeutic target in cancer. Mol Cancer Ther. 2015 Mar; 14(3):642-8.
Evans CG, Gestwicki JE. Correction to enantioselective organocatalytic hantzsch synthesis of polyhydroquinolines. Org Lett. 2014 11 21; 16(22):6040.
Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP. Targeting Hsp90/Hsp70-based protein quality control for treatment of adult onset neurodegenerative diseases. Annu Rev Pharmacol Toxicol. 2015; 55:353-71.
Jaeger AM, Makley LN, Gestwicki JE, Thiele DJ. Genomic heat shock element sequences drive cooperative human heat shock factor 1 DNA binding and selectivity. J Biol Chem. 2014 Oct 31; 289(44):30459-30469.
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. Epitope analysis following active immunization with tau proteins reveals immunogens implicated in tau pathogenesis. J Neuroinflammation. 2014 Sep 03; 11:152.
Rauch JN, Gestwicki JE. Rehabilitating mutant GCase. Chem Biol. 2014 Aug 14; 21(8):919-20.
Ung PM, Dunbar JB, Gestwicki JE, Carlson HA. An allosteric modulator of HIV-1 protease shows equipotent inhibition of wild-type and drug-resistant proteases. J Med Chem. 2014 Aug 14; 57(15):6468-78.
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. Hsp70-Bag3 interactions regulate cancer-related signaling networks. Cancer Res. 2014 Sep 01; 74(17):4731-40.
Pratt WB, Morishima Y, Gestwicki JE, Lieberman AP, Osawa Y. A model in which heat shock protein 90 targets protein-folding clefts: rationale for a new approach to neuroprotective treatment of protein folding diseases. Exp Biol Med (Maywood). 2014 Nov; 239(11):1405-13.
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. High-throughput screen of natural product extracts in a yeast model of polyglutamine proteotoxicity. Chem Biol Drug Des. 2014 Apr; 83(4):440-9.
Connarn JN, Assimon VA, Reed RA, Tse E, Southworth DR, Zuiderweg ER, Gestwicki JE, Sun D. The molecular chaperone Hsp70 activates protein phosphatase 5 (PP5) by binding the tetratricopeptide repeat (TPR) domain. J Biol Chem. 2014 Jan 31; 289(5):2908-17.
Rauch JN, Gestwicki JE. Binding of human nucleotide exchange factors to heat shock protein 70 (Hsp70) generates functionally distinct complexes in vitro. J Biol Chem. 2014 Jan 17; 289(3):1402-14.
Ung PM, Thompson AD, Chang L, Gestwicki JE, Carlson HA. Identification of key hinge residues important for nucleotide-dependent allostery in E. coli Hsp70/DnaK. PLoS Comput Biol. 2013; 9(11):e1003279.
Li X, Srinivasan SR, Connarn J, Ahmad A, Young ZT, Kabza AM, Zuiderweg ER, Sun D, Gestwicki JE. Analogs of the Allosteric Heat Shock Protein 70 (Hsp70) Inhibitor, MKT-077, as Anti-Cancer Agents. ACS Med Chem Lett. 2013 Nov 14; 4(11).
Rauch JN, Nie J, Buchholz TJ, Gestwicki JE, Kennedy RT. Development of a capillary electrophoresis platform for identifying inhibitors of protein-protein interactions. Anal Chem. 2013 Oct 15; 85(20):9824-31.
Smith MC, Scaglione KM, Assimon VA, Patury S, Thompson AD, Dickey CA, Southworth DR, Paulson HL, Gestwicki JE, Zuiderweg ER. The E3 ubiquitin ligase CHIP and the molecular chaperone Hsc70 form a dynamic, tethered complex. Biochemistry. 2013 Aug 13; 52(32):5354-64.
Cesa LC, Patury S, Komiyama T, Ahmad A, Zuiderweg ERP, Gestwicki JE. Inhibitors of difficult protein-protein interactions identified by high-throughput screening of multiprotein complexes. ACS Chem Biol. 2013 Sep 20; 8(9):1988-1997.
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. CSAR data set release 2012: ligands, affinities, complexes, and docking decoys. J Chem Inf Model. 2013 Aug 26; 53(8):1842-52.
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. Allosteric heat shock protein 70 inhibitors rapidly rescue synaptic plasticity deficits by reducing aberrant tau. Biol Psychiatry. 2013 Sep 01; 74(5):367-74.
Miyata Y, Li X, Lee HF, Jinwal UK, Srinivasan SR, Seguin SP, Young ZT, Brodsky JL, Dickey CA, Sun D, Gestwicki JE. 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 Chem Neurosci. 2013 Jun 19; 4(6):930-9.
Zuiderweg ER, Bertelsen EB, Rousaki A, Mayer MP, Gestwicki JE, Ahmad A. Allostery in the Hsp70 chaperone proteins. Top Curr Chem. 2013; 328:99-153.
Makley LN, Gestwicki JE. Expanding the number of 'druggable' targets: non-enzymes and protein-protein interactions. Chem Biol Drug Des. 2013 Jan; 81(1):22-32.
Assimon VA, Gillies AT, Rauch JN, Gestwicki JE. Hsp70 protein complexes as drug targets. Curr Pharm Des. 2013; 19(3):404-17.
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. Imbalance of Hsp70 family variants fosters tau accumulation. FASEB J. 2013 Apr; 27(4):1450-9.
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. Activation of Hsp70 reduces neurotoxicity by promoting polyglutamine protein degradation. Nat Chem Biol. 2013 Feb; 9(2):112-8.
Miyata Y, Rauch JN, Jinwal UK, Thompson AD, Srinivasan S, Dickey CA, Gestwicki JE. Cysteine reactivity distinguishes redox sensing by the heat-inducible and constitutive forms of heat shock protein 70. Chem Biol. 2012 Nov 21; 19(11):1391-9.
Gillies AT, Taylor R, Gestwicki JE. Synthetic lethal interactions in yeast reveal functional roles of J protein co-chaperones. Mol Biosyst. 2012 Nov; 8(11):2901-8.
Davis MJ, Gregorka B, Gestwicki JE, Swanson JA. Inducible renitence limits Listeria monocytogenes escape from vacuoles in macrophages. J Immunol. 2012 Nov 01; 189(9):4488-95.
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 Oct; 96(1):70-81.
Smith MC, Gestwicki JE. Features of protein-protein interactions that translate into potent inhibitors: topology, surface area and affinity. Expert Rev Mol Med. 2012 Jul 26; 14:e16.
Thompson AD, Scaglione KM, Prensner J, Gillies AT, Chinnaiyan A, Paulson HL, Jinwal UK, Dickey CA, Gestwicki JE. Analysis of the tau-associated proteome reveals that exchange of Hsp70 for Hsp90 is involved in tau degradation. ACS Chem Biol. 2012 Oct 19; 7(10):1677-86.
Thompson AD, Dugan A, Gestwicki JE, Mapp AK. Fine-tuning multiprotein complexes using small molecules. ACS Chem Biol. 2012 Aug 17; 7(8):1311-20.
Srinivasan SR, Gillies AT, Chang L, Thompson AD, Gestwicki JE. Molecular chaperones DnaK and DnaJ share predicted binding sites on most proteins in the E. coli proteome. Mol Biosyst. 2012 Sep; 8(9):2323-33.
Chafekar SM, Wisén S, Thompson AD, Echeverria A, Walter GM, Evans CG, Makley LN, Gestwicki JE, Duennwald ML. Pharmacological tuning of heat shock protein 70 modulates polyglutamine toxicity and aggregation. ACS Chem Biol. 2012 Sep 21; 7(9):1556-64.
Hammer ND, McGuffie BA, Zhou Y, Badtke MP, Reinke AA, Brännström K, Gestwicki JE, Olofsson A, Almqvist F, Chapman MR. The C-terminal repeating units of CsgB direct bacterial functional amyloid nucleation. J Mol Biol. 2012 Sep 21; 422(3):376-89.
Jinwal UK, Abisambra JF, Zhang J, Dharia S, O'Leary JC, Patel T, Braswell K, Jani T, Gestwicki JE, Dickey CA. Cdc37/Hsp90 protein complex disruption triggers an autophagic clearance cascade for TDP-43 protein. J Biol Chem. 2012 Jul 13; 287(29):24814-20.
Thompson AD, Makley LN, McMenimen K, Gestwicki JE. The three cornerstones of chemical biology: innovative probes, new discoveries, and enabling tools. ACS Chem Biol. 2012 May 18; 7(5):791-6.
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. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance. PLoS One. 2012; 7(4):e35566.
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. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr; 8(4):445-544.
Congdon EE, Wu JW, Myeku N, Figueroa YH, Herman M, Marinec PS, Gestwicki JE, Dickey CA, Yu WH, Duff KE. Methylthioninium chloride (methylene blue) induces autophagy and attenuates tauopathy in vitro and in vivo. Autophagy. 2012 Apr; 8(4):609-22.
Gestwicki JE, Garza D. Protein quality control in neurodegenerative disease. Prog Mol Biol Transl Sci. 2012; 107:327-53.
Thompson AD, Bernard SM, Skiniotis G, Gestwicki JE. Visualization and functional analysis of the oligomeric states of Escherichia coli heat shock protein 70 (Hsp70/DnaK). Cell Stress Chaperones. 2012 May; 17(3):313-27.
Walter GM, Smith MC, Wisén S, Basrur V, Elenitoba-Johnson KS, Duennwald ML, Kumar A, Gestwicki JE. Ordered assembly of heat shock proteins, Hsp26, Hsp70, Hsp90, and Hsp104, on expanded polyglutamine fragments revealed by chemical probes. J Biol Chem. 2011 Nov 25; 286(47):40486-93.
Miyata Y, Koren J, Kiray J, Dickey CA, Gestwicki JE. Molecular chaperones and regulation of tau quality control: strategies for drug discovery in tauopathies. Future Med Chem. 2011 Sep; 3(12):1523-37.
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. Ube2w and ataxin-3 coordinately regulate the ubiquitin ligase CHIP. Mol Cell. 2011 Aug 19; 43(4):599-612.
Morishima Y, Lau M, Peng HM, Miyata Y, Gestwicki JE, Pratt WB, Osawa Y. Heme-dependent activation of neuronal nitric oxide synthase by cytosol is due to an Hsp70-dependent, thioredoxin-mediated thiol-disulfide interchange in the heme/substrate binding cleft. Biochemistry. 2011 Aug 23; 50(33):7146-56.
Rousaki A, Miyata Y, Jinwal UK, Dickey CA, Gestwicki JE, Zuiderweg ER. Allosteric drugs: the interaction of antitumor compound MKT-077 with human Hsp70 chaperones. J Mol Biol. 2011 Aug 19; 411(3):614-32.
Reinke AA, Gestwicki JE. Insight into amyloid structure using chemical probes. Chem Biol Drug Des. 2011 Jun; 77(6):399-411.
Evans CG, Smith MC, Carolan JP, Gestwicki JE. Improved synthesis of 15-deoxyspergualin analogs using the Ugi multi-component reaction. Bioorg Med Chem Lett. 2011 May 01; 21(9):2587-90.
Chang L, Miyata Y, Ung PM, Bertelsen EB, McQuade TJ, Carlson HA, Zuiderweg ER, Gestwicki JE. Chemical screens against a reconstituted multiprotein complex: myricetin blocks DnaJ regulation of DnaK through an allosteric mechanism. Chem Biol. 2011 Feb 25; 18(2):210-21.
Reinke AA, Ung PM, Quintero JJ, Carlson HA, Gestwicki JE. Chemical probes that selectively recognize the earliest Aβ oligomers in complex mixtures. J Am Chem Soc. 2010 Dec 22; 132(50):17655-7.
Evans CG, Jinwal UK, Makley LN, Dickey CA, Gestwicki JE. Identification of dihydropyridines that reduce cellular tau levels. Chem Commun (Camb). 2011 Jan 07; 47(1):529-31.
Bainor A, Chang L, McQuade TJ, Webb B, Gestwicki JE. Bicinchoninic acid (BCA) assay in low volume. Anal Biochem. 2011 Mar 15; 410(2):310-2.
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. Phenothiazine-mediated rescue of cognition in tau transgenic mice requires neuroprotection and reduced soluble tau burden. Mol Neurodegener. 2010 Nov 01; 5:45.
Xu T, Johnson CA, Gestwicki JE, Kumar A. Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization. Nat Protoc. 2010 Nov; 5(11):1831-43.
Miyata Y, Chang L, Bainor A, McQuade TJ, Walczak CP, Zhang Y, Larsen MJ, Kirchhoff P, Gestwicki JE. High-throughput screen for Escherichia coli heat shock protein 70 (Hsp70/DnaK): ATPase assay in low volume by exploiting energy transfer. J Biomol Screen. 2010 Dec; 15(10):1211-9.
Reinke AA, Abulwerdi GA, Gestwicki JE. Quantifying prefibrillar amyloids in vitro by using a "thioflavin-like" spectroscopic method. Chembiochem. 2010 Sep 03; 11(13):1889-95.
Evans CG, Chang L, Gestwicki JE. Heat shock protein 70 (hsp70) as an emerging drug target. J Med Chem. 2010 Jun 24; 53(12):4585-602.
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 Jun 18; 5(6):611-22.
Chang L, Thompson AD, Ung P, Carlson HA, Gestwicki JE. Mutagenesis reveals the complex relationships between ATPase rate and the chaperone activities of Escherichia coli heat shock protein 70 (Hsp70/DnaK). J Biol Chem. 2010 Jul 09; 285(28):21282-91.
Wang AM, Morishima Y, Clapp KM, Peng HM, Pratt WB, Gestwicki JE, Osawa Y, Lieberman AP. Inhibition of hsp70 by methylene blue affects signaling protein function and ubiquitination and modulates polyglutamine protein degradation. J Biol Chem. 2010 May 21; 285(21):15714-23.
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. Hsc70 rapidly engages tau after microtubule destabilization. J Biol Chem. 2010 May 28; 285(22):16798-805.
Gestwicki JE. Special series: Molecular chaperones in protein folding and disease. Biopolymers. 2010 Mar; 93(3):209-10.
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. Facilitating Akt clearance via manipulation of Hsp70 activity and levels. J Biol Chem. 2010 Jan 22; 285(4):2498-505.
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. Chemical manipulation of hsp70 ATPase activity regulates tau stability. J Neurosci. 2009 Sep 30; 29(39):12079-88.
Reinke AA, Seh HY, Gestwicki JE. A chemical screening approach reveals that indole fluorescence is quenched by pre-fibrillar but not fibrillar amyloid-beta. Bioorg Med Chem Lett. 2009 Sep 01; 19(17):4952-7.
Marinec PS, Evans CG, Gibbons GS, Tarnowski MA, Overbeek DL, Gestwicki JE. Synthesis of orthogonally reactive FK506 derivatives via olefin cross metathesis. Bioorg Med Chem. 2009 Aug 15; 17(16):5763-8.
Evans CG, Gestwicki JE. Enantioselective organocatalytic Hantzsch synthesis of polyhydroquinolines. Org Lett. 2009 07 16; 11(14):2957-9.
Bertelsen EB, Chang L, Gestwicki JE, Zuiderweg ER. Solution conformation of wild-type E. coli Hsp70 (DnaK) chaperone complexed with ADP and substrate. Proc Natl Acad Sci U S A. 2009 May 26; 106(21):8471-6.
Lexa KW, Damm KL, Quintero JJ, Gestwicki JE, Carlson HA. Clarifying allosteric control of flap conformations in the 1TW7 crystal structure of HIV-1 protease. Proteins. 2009 Mar; 74(4):872-80.
Marinec PS, Chen L, Barr KJ, Mutz MW, Crabtree GR, Gestwicki JE. FK506-binding protein (FKBP) partitions a modified HIV protease inhibitor into blood cells and prolongs its lifetime in vivo. Proc Natl Acad Sci U S A. 2009 Feb 03; 106(5):1336-41.
Patury S, Geda P, Dobry CJ, Kumar A, Gestwicki JE. Conditional nuclear import and export of yeast proteins using a chemical inducer of dimerization. Cell Biochem Biophys. 2009; 53(3):127-34.
Patury S, Miyata Y, Gestwicki JE. Pharmacological targeting of the Hsp70 chaperone. Curr Top Med Chem. 2009; 9(15):1337-51.
Damm KL, Ung PM, Quintero JJ, Gestwicki JE, Carlson HA. A poke in the eye: inhibiting HIV-1 protease through its flap-recognition pocket. Biopolymers. 2008 Aug; 89(8):643-52.
Geda P, Patury S, Ma J, Bharucha N, Dobry CJ, Lawson SK, Gestwicki JE, Kumar A. A small molecule-directed approach to control protein localization and function. Yeast. 2008 Aug; 25(8):577-94.
Gestwicki JE. The interface of chemistry and biology is actually a continuum. ACS Chem Biol. 2008 Jun 20; 3(6):328-34.
Marinec PS, Lancia JK, Gestwicki JE. Bifunctional molecules evade cytochrome P(450) metabolism by forming protective complexes with FK506-binding protein. Mol Biosyst. 2008 Jun; 4(6):571-8.
Wisén S, Gestwicki JE. Identification of small molecules that modify the protein folding activity of heat shock protein 70. Anal Biochem. 2008 Mar 15; 374(2):371-7.
Wisén S, Androsavich J, Evans CG, Chang L, Gestwicki JE. Chemical modulators of heat shock protein 70 (Hsp70) by sequential, microwave-accelerated reactions on solid phase. Bioorg Med Chem Lett. 2008 Jan 01; 18(1):60-5.
Hadden MK, Galam L, Gestwicki JE, Matts RL, Blagg BS. Derrubone, an inhibitor of the Hsp90 protein folding machinery. J Nat Prod. 2007 Dec; 70(12):2014-8.
Gestwicki JE, Marinec PS. Chemical control over protein-protein interactions: beyond inhibitors. Comb Chem High Throughput Screen. 2007 Sep; 10(8):667-75.
Reinke AA, Gestwicki JE. Structure-activity relationships of amyloid beta-aggregation inhibitors based on curcumin: influence of linker length and flexibility. Chem Biol Drug Des. 2007 Sep; 70(3):206-15.
Chang L, Bertelsen EB, Wisén S, Larsen EM, Zuiderweg ER, Gestwicki JE. High-throughput screen for small molecules that modulate the ATPase activity of the molecular chaperone DnaK. Anal Biochem. 2008 Jan 15; 372(2):167-76.
Stankunas K, Bayle JH, Havranek JJ, Wandless TJ, Baker D, Crabtree GR, Gestwicki JE. Rescue of degradation-prone mutants of the FK506-rapamycin binding (FRB) protein with chemical ligands. Chembiochem. 2007 Jul 09; 8(10):1162-9.
Rubinsztein DC, Gestwicki JE, Murphy LO, Klionsky DJ. Potential therapeutic applications of autophagy. Nat Rev Drug Discov. 2007 Apr; 6(4):304-12.
Evans CG, Wisén S, Gestwicki JE. Heat shock proteins 70 and 90 inhibit early stages of amyloid beta-(1-42) aggregation in vitro. J Biol Chem. 2006 Nov 03; 281(44):33182-91.
Gestwicki JE. Reclamation of proteins from the cellular scrap heap. ACS Chem Biol. 2006 May 23; 1(4):201-3.
Kiessling LL, Gestwicki JE, Strong LE. Synthetic multivalent ligands as probes of signal transduction. Angew Chem Int Ed Engl. 2006 Apr 03; 45(15):2348-68.
Bayle JH, Grimley JS, Stankunas K, Gestwicki JE, Wandless TJ, Crabtree GR. Rapamycin analogs with differential binding specificity permit orthogonal control of protein activity. Chem Biol. 2006 Jan; 13(1):99-107.
Bose M, Gestwicki JE, Devasthali V, Crabtree GR, Graef IA. 'Nature-inspired' drug-protein complexes as inhibitors of Abeta aggregation. Biochem Soc Trans. 2005 Aug; 33(Pt 4):543-7.
Gestwicki JE. Target identification for a promising anti-lupus drug. Chem Biol. 2005 Apr; 12(4):414-5.
Gestwicki JE, Crabtree GR, Graef IA. Harnessing chaperones to generate small-molecule inhibitors of amyloid beta aggregation. Science. 2004 Oct 29; 306(5697):865-9.
Chang CP, Neilson JR, Bayle JH, Gestwicki JE, Kuo A, Stankunas K, Graef IA, Crabtree GR. A field of myocardial-endocardial NFAT signaling underlies heart valve morphogenesis. Cell. 2004 Sep 03; 118(5):649-63.
Stankunas K, Bayle JH, Gestwicki JE, Lin YM, Wandless TJ, Crabtree GR. Conditional protein alleles using knockin mice and a chemical inducer of dimerization. Mol Cell. 2003 Dec; 12(6):1615-24.
Gestwicki JE, Cairo CW, Borrok MJ, Kiessling LL. Visualization and characterization of receptor clusters by transmission electron microscopy. Methods Enzymol. 2003; 362:301-12.
Gestwicki JE, Cairo CW, Strong LE, Oetjen KA, Kiessling LL. Influencing receptor-ligand binding mechanisms with multivalent ligand architecture. J Am Chem Soc. 2002 Dec 18; 124(50):14922-33.
Lamanna AC, Gestwicki JE, Strong LE, Borchardt SL, Owen RM, Kiessling LL. Conserved amplification of chemotactic responses through chemoreceptor interactions. J Bacteriol. 2002 Sep; 184(18):4981-7.
Owen RM, Gestwicki JE, Young T, Kiessling LL. Synthesis and applications of end-labeled neoglycopolymers. Org Lett. 2002 Jul 11; 4(14):2293-6.
Gestwicki JE, Cairo CW, Mann DA, Owen RM, Kiessling LL. Selective immobilization of multivalent ligands for surface plasmon resonance and fluorescence microscopy. Anal Biochem. 2002 Jun 15; 305(2):149-55.
Cairo CW, Gestwicki JE, Kanai M, Kiessling LL. Control of multivalent interactions by binding epitope density. J Am Chem Soc. 2002 Feb 27; 124(8):1615-9.
Gestwicki JE, Strong LE, Cairo CW, Boehm FJ, Kiessling LL. Cell aggregation by scaffolded receptor clusters. Chem Biol. 2002 Feb; 9(2):163-9.
Gestwicki JE, Kiessling LL. Inter-receptor communication through arrays of bacterial chemoreceptors. Nature. 2002 Jan 03; 415(6867):81-4.
Gestwicki JE, Hsieh HV, Pitner JB. Using receptor conformational change to detect low molecular weight analytes by surface plasmon resonance. Anal Chem. 2001 Dec 01; 73(23):5732-7.
Gestwicki JE, Strong LE, Borchardt SL, Cairo CW, Schnoes AM, Kiessling LL. Designed potent multivalent chemoattractants for Escherichia coli. Bioorg Med Chem. 2001 Sep; 9(9):2387-93.
Gestwicki JE, Strong LE, Kiessling LL. Visualization of Single Multivalent Receptor-Ligand Complexes by Transmission Electron Microscopy The authors thank Colleen Lavin (UW Madison, Microscopy Resource) and Kim Dickson for experimental support. This work was supported in part by the NIH (GM 55984). J.E.G. acknowledges the NIH Biotechnology Training Grant for support (T32GM08349). L.E.S. was supported by an NIH predoctoral fellowship (GM 18750). Angew Chem Int Ed Engl. 2000 Dec 15; 39(24):4567-4570.
Kiessling LL, Gestwicki JE, Strong LE. Synthetic multivalent ligands in the exploration of cell-surface interactions. Curr Opin Chem Biol. 2000 Dec; 4(6):696-703.
Gestwicki JE, Lamanna AC, Harshey RM, McCarter LL, Kiessling LL, Adler J. Evolutionary conservation of methyl-accepting chemotaxis protein location in Bacteria and Archaea. J Bacteriol. 2000 Nov; 182(22):6499-502.
Hoag KA, Clise-Dwyer K, Lim YH, Nashold FE, Gestwicki J, Cancro MP, Hayes CE. A quantitative-trait locus controlling peripheral B-cell deficiency maps to mouse Chromosome 15. Immunogenetics. 2000 Sep; 51(11):924-9.
Maki N, Gestwicki JE, Lake EM, Kiessling LL, Adler J. Motility and chemotaxis of filamentous cells of Escherichia coli. J Bacteriol. 2000 Aug; 182(15):4337-42.
Gestwicki JE, Strong LE, Kiessling LL. Tuning chemotactic responses with synthetic multivalent ligands. Chem Biol. 2000 Aug; 7(8):583-91.
Kabza KG, Chapados BR, Gestwicki JE, McGrath JL. Microwave-induced esterification using heterogeneous acid catalyst in a low dielectric constant medium J Org Chem. 2000 Feb 25; 65(4):1210-4.
Gordon EJ, Gestwicki JE, Strong LE, Kiessling LL. Synthesis of end-labeled multivalent ligands for exploring cell-surface-receptor-ligand interactions. Chem Biol. 2000 Jan; 7(1):9-16.