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. 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.
    View on PubMed
  2. 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.
    View on PubMed
  3. 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.
    View on PubMed
  4. 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.
    View on PubMed
  5. 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.
    View on PubMed
  6. 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.
    View on PubMed
  7. 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.
    View on PubMed
  8. 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.
    View on PubMed
  9. 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.
    View on PubMed
  10. 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.
    View on PubMed
  11. 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.
    View on PubMed
  12. 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.
    View on PubMed
  13. 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.
    View on PubMed
  14. 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.
    View on PubMed
  15. 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.
    View on PubMed
  16. Cesa LC, Mapp AK, Gestwicki JE. Direct and Propagated Effects of Small Molecules on Protein-Protein Interaction Networks. Front Bioeng Biotechnol. 2015; 3:119.
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  17. 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.
    View on PubMed
  18. 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.
    View on PubMed
  19. 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.
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  20. Assimon VA, Shao H, Garneau-Tsodikova S, Gestwicki JE. Concise Synthesis of Spergualin-Inspired Molecules With Broad-Spectrum Antibiotic Activity. Medchemcomm. 2015 May 1; 6(5):912-918.
    View on PubMed

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