University of California San Francisco
Helen Diller Family Comprehensive Cancer Center
Peter Walter, PhD

Peter Walter, PhD

Professor and Chair, Department of Biochemistry/Biophysics, UCSF; Investigator, Howard Hughes Medical Institute

Cancer Center Program Memberships

Hematopoietic Malignancies

Research Summary

My laboratory seeks a molecular understanding of how cells control the quality of their proteins and organelles during homeostasis and stress. We are identifying the machinery and mechanisms that ensure proper protein synthesis, folding, and targeting, as well as the pathways that allow organelles to communicate and regulate their abundance. Additionally, we aim to understand how the rewiring of these processes leads to, or prevents, the progression of disease. My laboratory uses a diverse array of approaches, ranging from biochemical reconstitution to genetics, to fuel our search for fundamental discoveries in cell biology. An NIH R01 (GM32384) has been funding our biochemical and mechanistic efforts on protein targeting and translocation since the inception of my group in 1983. A second NIGMS R01 grant funded our efforts on genetic approaches on the topic (R01 GM37485). I decided to return and not renew that grant in 2000, after I was appointed as HHMI Investigator. We maintained GM32384 at a modest funding level. Website: walterlab.ucsf.edu

Education

Freie Universitat Berlin, Germany, Vordiplom, 1976, Chemistry
Vanderbilt University, Nashville, TN, M.Sc., 1977, Organic Chemistry
The Rockefeller University, New York, Ph.D., 1981, Cell Biology


Professional Experience

  • 1976-1977
    Direct Exchange Fellow, Vanderbilt University, in the laboratory of Dr. T.M. Harris
  • 1977-1981
    Graduate Fellow, The Rockefeller University, in the laboratory of Dr. G. Blobel
  • 1981-1982
    Postdoctoral Fellow, The Rockefeller University, in the laboratory of Dr. G. Blobel
  • 1982-1983
    Assistant Professor, Laboratory of Cell Biology, The Rockefeller University
  • 1983-1986
    Assistant Professor, Department of Biochemistry & Biophysics, University of California, San Francisco
  • 1986-1991
    Associate Professor, Department of Biochemistry & Biophysics, UCSF
  • 1991-present
    Professor, Department of Biochemistry & Biophysics, UCSF
  • 1997-present
    Investigator, Howard Hughes Medical Institute
  • 2001-present
    Chair, Department of Biochemistry & Biophysics Department, UCSF

Honors & Awards

  • 1983
    Searle Scholar Award
  • 1988
    Eli Lilly Award for Fundamental Research in Biological Chemistry
  • 1988
    Passano Award
  • 1989
    Alfred P. Sloan Award
  • 1993
    NIH MERIT Award
  • 1996
    Harvey Lecturer, Rockefeller University, New York
  • 1998
    American Academy of Microbiology (elected Fellow)
  • 1998
    Feodor-Lynen-Lecture, Mosbach Kolloquium, Germany
  • 2001
    American Academy of Arts & Sciences (elected Fellow)
  • 2004
    National Academy of Sciences (elected Member)
  • 2004
    European Molecular Biology Organization (elected Associate Member)
  • 2004
    Virchow Lecture, Universität Würzburg
  • 2005
    Wiley Prize in Biomedical Sciences (with Dr. Kazutoshi Mori)
  • 2005
    George E. Palade Distinguished Lecture, Wayne State University School of Medicine
  • 2006
    47th Stadtler Lecture, University of Texas
  • 2006
    Leopoldina Academy of Scientists (elected member)
  • 2012
    Paul Ehrlich and Ludwig Darmstaedter Prize, UCSF
  • 2014
    Lasker Basic Medical Research Award
  • 2014
    Shaw Prize in Life Science and Medicine, UCSF
  • 2015
    Vilcek Prize in Biomedical Science

Selected Publications

  1. Harnoss JM, Le Thomas A, Shemorry A, Marsters SA, Lawrence DA, Lu M, Chen YA, Qing J, Totpal K, Kan D, Segal E, Merchant M, Reichelt M, Ackerly Wallweber H, Wang W, Clark K, Kaufman S, Beresini MH, Laing ST, Sandoval W, Lorenzo M, Wu J, Ly J, De Bruyn T, Heidersbach A, Haley B, Gogineni A, Weimer RM, Lee D, Braun MG, Rudolph J, VanWyngarden MJ, Sherbenou DW, Gomez-Bougie P, Amiot M, Acosta-Alvear D, Walter P, Ashkenazi A. Disruption of IRE1a through its kinase domain attenuates multiple myeloma. Proc Natl Acad Sci U S A. 2019 Aug 01.
    View on PubMed
  2. Peschek J, Walter P. tRNA ligase structure reveals kinetic competition between non-conventional mRNA splicing and mRNA decay. Elife. 2019 Jun 25; 8.
    View on PubMed
  3. Torres SE, Gallagher CM, Plate L, Gupta M, Liem CR, Guo X, Tian R, Stroud RM, Kampmann M, Weissman JS, Walter P. Ceapins block the unfolded protein response sensor ATF6a by inducing a neomorphic inter-organelle tether. Elife. 2019 May 31; 8.
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  4. Bielecki J, Hantke MF, Daurer BJ, Reddy HKN, Hasse D, Larsson DSD, Gunn LH, Svenda M, Munke A, Sellberg JA, Flueckiger L, Pietrini A, Nettelblad C, Lundholm I, Carlsson G, Okamoto K, Timneanu N, Westphal D, Kulyk O, Higashiura A, van der Schot G, Loh ND, Wysong TE, Bostedt C, Gorkhover T, Iwan B, Seibert MM, Osipov T, Walter P, Hart P, Bucher M, Ulmer A, Ray D, Carini G, Ferguson KR, Andersson I, Andreasson J, Hajdu J, Maia FRNC. Electrospray sample injection for single-particle imaging with x-ray lasers. Sci Adv. 2019 May; 5(5):eaav8801.
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  5. Kenner LR, Anand AA, Nguyen HC, Myasnikov AG, Klose CJ, McGeever LA, Tsai JC, Miller-Vedam LE, Walter P, Frost A. eIF2B-catalyzed nucleotide exchange and phosphoregulation by the integrated stress response. Science. 2019 05 03; 364(6439):491-495.
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  6. Rabouw HH, Langereis MA, Anand AA, Visser LJ, de Groot RJ, Walter P, van Kuppeveld FJM. Small molecule ISRIB suppresses the integrated stress response within a defined window of activation. Proc Natl Acad Sci U S A. 2019 02 05; 116(6):2097-2102.
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  7. Karagöz GE, Acosta-Alvear D, Walter P. The Unfolded Protein Response: Detecting and Responding to Fluctuations in the Protein-Folding Capacity of the Endoplasmic Reticulum. Cold Spring Harb Perspect Biol. 2019 Jan 22.
    View on PubMed
  8. Acosta-Alvear D, Karagöz GE, Fröhlich F, Li H, Walther TC, Walter P. The unfolded protein response and endoplasmic reticulum protein targeting machineries converge on the stress sensor IRE1. Elife. 2018 12 24; 7.
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  9. Lam M, Lawrence DA, Ashkenazi A, Walter P. Confirming a critical role for death receptor 5 and caspase-8 in apoptosis induction by endoplasmic reticulum stress. Cell Death Differ. 2018 Aug; 25(8):1530-1531.
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  10. Li W, Okreglak V, Peschek J, Kimmig P, Zubradt M, Weissman JS, Walter P. Engineering ER-stress dependent non-conventional mRNA splicing. Elife. 2018 07 09; 7.
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  11. Nguyen HG, Conn CS, Kye Y, Xue L, Forester CM, Cowan JE, Hsieh AC, Cunningham JT, Truillet C, Tameire F, Evans MJ, Evans CP, Yang JC, Hann B, Koumenis C, Walter P, Carroll PR, Ruggero D. Development of a stress response therapy targeting aggressive prostate cancer. Sci Transl Med. 2018 May 02; 10(439).
    View on PubMed
  12. Walter P, Anderson D. Günter Blobel (1936-2018). Science. 2018 Apr 27; 360(6387):383.
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  13. Cho JA, Lee AH, Platzer B, Cross BCS, Gardner BM, De Luca H, Luong P, Harding HP, Glimcher LH, Walter P, Fiebiger E, Ron D, Kagan JC, Lencer WI. Retraction Notice to: The Unfolded Protein Response Element IRE1a Senses Bacterial Proteins Invading the ER to Activate RIG-I and Innate Immune Signaling. Cell Host Microbe. 2018 04 11; 23(4):571.
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  14. Tsai JC, Miller-Vedam LE, Anand AA, Jaishankar P, Nguyen HC, Renslo AR, Frost A, Walter P. Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule. Science. 2018 03 30; 359(6383).
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  15. Karagöz GE, Acosta-Alvear D, Nguyen HT, Lee CP, Chu F, Walter P. An unfolded protein-induced conformational switch activates mammalian IRE1. Elife. 2017 10 03; 6.
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  16. Guydosh NR, Kimmig P, Walter P, Green R. Regulated Ire1-dependent mRNA decay requires no-go mRNA degradation to maintain endoplasmic reticulum homeostasis in S. pombe. Elife. 2017 09 25; 6.
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  17. Cohen N, Breker M, Bakunts A, Pesek K, Chas A, Argemí J, Orsi A, Gal L, Chuartzman S, Wigelman Y, Jonas F, Walter P, Ernst R, Aragón T, van Anken E, Schuldiner M. Iron affects Ire1 clustering propensity and the amplitude of endoplasmic reticulum stress signaling. J Cell Sci. 2017 Oct 01; 130(19):3222-3233.
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  18. Chou A, Krukowski K, Jopson T, Zhu PJ, Costa-Mattioli M, Walter P, Rosi S. Inhibition of the integrated stress response reverses cognitive deficits after traumatic brain injury. Proc Natl Acad Sci U S A. 2017 08 01; 114(31):E6420-E6426.
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  19. Castillo K, Rojas-Rivera D, Lisbona F, Caballero B, Nassif M, Court FA, Schuck S, Ibar C, Walter P, Sierralta J, Glavic A, Hetz C. BAX inhibitor-1 regulates autophagy by controlling the IRE1a branch of the unfolded protein response. EMBO J. 2017 06 01; 36(11):1640.
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  20. Tufanli O, Telkoparan Akillilar P, Acosta-Alvear D, Kocaturk B, Onat UI, Hamid SM, Çimen I, Walter P, Weber C, Erbay E. Targeting IRE1 with small molecules counteracts progression of atherosclerosis. Proc Natl Acad Sci U S A. 2017 02 21; 114(8):E1395-E1404.
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