Jason E. Gestwicki, PhD

A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
Jason E. Gestwicki, PhD

Associate Professor, Pharmaceutical Chemistry, UCSF

Jason.Gestwicki@ucsf.edu

Phone: (415) 502-7121
Box 0518, UCSF
San Francisco, CA 94143-0518

UCSF Profiles

Research Summary

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.

Education

State University of New York - Fredonia, B.S., 1997, Chemistry
University of Wisconsin – Madison (with Laura L. Kiessling), PhD, 2002, Biochemistry
Stanford University (with Gerald R. Crabtree), 2005, Post-doctoral, Chemical Biology


Professional Experience

  • 2013 – present
    University of California at San Francisco Associate Professor in Residence, Department of Pharmaceutical Chemistry Associate Professor, Institute for Neurodegenerative Diseases
  • 2011 - 2013
    University of Michigan Associate Professor, Departments of Pathology and Biological Chemistry William B. Pratt Collegiate Professor, Life Sciences Institute Director, Center for Chemical Genomics (CCG)
  • 2005 – 2011
    University of Michigan Assistant Professor, Departments of Pathology and Biological Chemistry Research Assistant Professor, Life Sciences Institute

Honors & Awards

  • 2015
    UCSF School of Pharmacy, Excellence in Teaching
  • 2014
    Named “Young Innovator” at UCSF
  • 2012
    Elected Fellow, American Association for the Advancement of Science (AAAS)
  • 2009
    National Science Foundation CAREER award
  • 2006
    McKnight Foundation Brain Disorders Award (with Andrew Lieberman and William Pratt)
  • 2005
    Biological Sciences Scholar (University of Michigan)
  • 2001
    Sigrid Liermo Award (Departmental Service; UW Madison)
  • 1998
    National Institutes of Health Biotechnology Training Program Fellowship

Selected Publications

  1. Young ZT, Mok SA, Gestwicki JE. Therapeutic Strategies for Restoring Tau Homeostasis. Cold Spring Harb Perspect Med. 2017 Feb 03.
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  2. Rauch JN, Olson SH, Gestwicki JE. Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules. Cold Spring Harb Perspect Med. 2016 Dec 09.
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  3. 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. 2016 Nov 21.
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  4. 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. 2016 Oct 3.
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  5. Costa MD, 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 Sep 19.
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  6. 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 Oct 15; 76(20):5926-5932.
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  7. 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 Aug 18; 23(8):992-1001.
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  8. 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 Sep 16; 291(38):19848-57.
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  9. 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 Aug 16; 88(16):8272-8.
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  10. Dunyak BM, Gestwicki JE. Peptidyl-Proline Isomerases (PPIases): Targets for Natural Products and Natural Product-Inspired Compounds. J Med Chem. 2016 Nov 10; 59(21):9622-9644.
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  11. 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 Aug 9; 113(32):9015-20.
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  12. 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 Aug 26; 291(35):18096-106.
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  13. 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 Jul 15; 11(7):2041-8.
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  14. 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 May 19; 23(5):561-6.
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  15. Li X, Shao H, Taylor IR, Gestwicki JE. Targeting Allosteric Control Mechanisms in Heat Shock Protein 70 (Hsp70). Curr Top Med Chem. 2016 Apr 13.
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  16. 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.
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  17. 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.
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  18. 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 8; 54(48):7120-31.
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  19. 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):1108-23.
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  20. 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 a-crystallin partially restores transparency in cataract models. Science. 2015 Nov 6; 350(6261):674-7.
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