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

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. Wang L, Walter P. Msp1/ATAD1 in Protein Quality Control and Regulation of Synaptic Activities. Annu Rev Cell Dev Biol. 2020 Sep 04.
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  2. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Zimanyi M, Deshpande I, Liang J, Anand AA, Dobzinski N, Zha BS, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Gupta S, Simoneau CR, Leon K, White KM, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, Walter P, Manglik A. An ultra-high affinity synthetic nanobody blocks SARS-CoV-2 infection by locking Spike into an inactive conformation. bioRxiv. 2020 Aug 10.
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  3. Rabouw HH, Visser LJ, Passchier TC, Langereis MA, Liu F, Giansanti P, van Vliet ALW, Dekker JG, van der Grein SG, Saucedo JG, Anand AA, Trellet ME, Bonvin AMJJ, Walter P, Heck AJR, de Groot RJ, van Kuppeveld FJM. Inhibition of the integrated stress response by viral proteins that block p-eIF2-eIF2B association. Nat Microbiol. 2020 Jul 20.
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  4. Dufey E, Bravo-San Pedro JM, Eggers C, González-Quiroz M, Urra H, Sagredo AI, Sepulveda D, Pihán P, Carreras-Sureda A, Hazari Y, Sagredo EA, Gutierrez D, Valls C, Papaioannou A, Acosta-Alvear D, Campos G, Domingos PM, Pedeux R, Chevet E, Alvarez A, Godoy P, Walter P, Glavic A, Kroemer G, Hetz C. Genotoxic stress triggers the activation of IRE1a-dependent RNA decay to modulate the DNA damage response. Nat Commun. 2020 05 14; 11(1):2401.
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  5. Costa-Mattioli M, Walter P. The integrated stress response: From mechanism to disease. Science. 2020 04 24; 368(6489).
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  6. Harnoss JM, Le Thomas A, Reichelt M, Guttman O, Wu TD, Marsters SA, Shemorry A, Lawrence DA, Kan D, Segal E, Merchant M, Totpal K, Crocker LM, Mesh K, Dohse M, Solon M, Modrusan Z, Rudolph J, Koeppen H, Walter P, Ashkenazi A. IRE1a Disruption in Triple-Negative Breast Cancer Cooperates with Antiangiogenic Therapy by Reversing ER Stress Adaptation and Remodeling the Tumor Microenvironment. Cancer Res. 2020 Jun 01; 80(11):2368-2379.
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  7. Weihan Li, Kelly Crotty, Diego Garrido Ruiz, Jirka Peschek, Peter Walter. Regulating ER protein homeostasis by differentially processing mRNAs. The FASEB Journal. 2020 Apr 1; 34(S1):1-1.
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  8. Carter SD, Hampton CM, Langlois R, Melero R, Farino ZJ, Calderon MJ, Li W, Wallace CT, Tran NH, Grassucci RA, Siegmund SE, Pemberton J, Morgenstern TJ, Eisenman L, Aguilar JI, Greenberg NL, Levy ES, Yi E, Mitchell WG, Rice WJ, Wigge C, Pilli J, George EW, Aslanoglou D, Courel M, Freyberg RJ, Javitch JA, Wills ZP, Area-Gomez E, Shiva S, Bartolini F, Volchuk A, Murray SA, Aridor M, Fish KN, Walter P, Balla T, Fass D, Wolf SG, Watkins SC, Carazo JM, Jensen GJ, Frank J, Freyberg Z. Ribosome-associated vesicles: A dynamic subcompartment of the endoplasmic reticulum in secretory cells. Sci Adv. 2020 04; 6(14):eaay9572.
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  9. Krukowski K, Nolan A, Frias ES, Grue K, Becker M, Ureta G, Delgado L, Bernales S, Sohal VS, Walter P, Rosi S. Integrated Stress Response Inhibitor Reverses Sex-Dependent Behavioral and Cell-Specific Deficits after Mild Repetitive Head Trauma. J Neurotrauma. 2020 Jun 01; 37(11):1370-1380.
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  10. Wang L, Myasnikov A, Pan X, Walter P. Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction. Elife. 2020 Jan 30; 9.
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  11. Lam M, Marsters SA, Ashkenazi A, Walter P. Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress. Elife. 2020 Jan 06; 9.
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  12. Belyy V, Tran NH, Walter P. Quantitative microscopy reveals dynamics and fate of clustered IRE1a. Proc Natl Acad Sci U S A. 2020 01 21; 117(3):1533-1542.
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  13. Zhu PJ, Khatiwada S, Cui Y, Reineke LC, Dooling SW, Kim JJ, Li W, Walter P, Costa-Mattioli M. Activation of the ISR mediates the behavioral and neurophysiological abnormalities in Down syndrome. Science. 2019 11 15; 366(6467):843-849.
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  14. Anand AA, Walter P. Structural insights into ISRIB, a memory-enhancing inhibitor of the integrated stress response. FEBS J. 2020 Jan; 287(2):239-245.
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  15. Perlaza K, Toutkoushian H, Boone M, Lam M, Iwai M, Jonikas MC, Walter P, Ramundo S. The Mars1 kinase confers photoprotection through signaling in the chloroplast unfolded protein response. Elife. 2019 10 15; 8.
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  16. Göke A, Schrott S, Mizrak A, Belyy V, Osman C, Walter P. Mrx6 regulates mitochondrial DNA copy number in Saccharomyces cerevisiae by engaging the evolutionarily conserved Lon protease Pim1. Mol Biol Cell. 2020 03 19; 31(7):527-545.
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  17. Walter P, Mullins D. From symbiont to parasite: the evolution of for-profit science publishing. Mol Biol Cell. 2019 09 15; 30(20):2537-2542.
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  18. 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 09 03; 11(9).
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  19. Khanal Lamichhane A, Garraffo HM, Cai H, Walter PJ, Kwon-Chung KJ, Chang YC. A Novel Role of Fungal Type I Myosin in Regulating Membrane Properties and Its Association with d-Amino Acid Utilization in Cryptococcus gattii. mBio. 2019 08 27; 10(4).
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  20. Doolittle MH, Neher SB, Ben-Zeev O, Ling-Liao J, Gallagher CM, Hosseini M, Yin F, Wong H, Walter P, Péterfy M. Withdrawal: Lipase maturation factor LMF1, membrane topology and interaction with lipase proteins in the endoplasmic reticulum. J Biol Chem. 2019 Aug 09; 294(32):12263.
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