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

Research Funding

  • September 30, 1996 - June 30, 2016 - Comprehensive Biology: Exploiting the Yeast Genome, Co-Investigator. Sponsor: NIH, Sponsor Award ID: P41RR011823
  • September 30, 2012 - July 31, 2015 - Structural Basis of Protein Homeostasis, Principal Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: U01GM098254
  • September 24, 2004 - July 31, 2009 - Membrane Protein Expression Center, Co-Investigator. Sponsor: NIH/NIGMS, Sponsor Award ID: P50GM073210
  • June 1, 2007 - May 31, 2008 - Stress Proteins in Growth, Development &Disease 2007Gordon Research Conference, Principal Investigator. Sponsor: NIH/NIA, Sponsor Award ID: R13AG030760

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. Christopher Jakubke, Rodaria Roussou, Andreas Maiser, Christina Schug, Felix Thoma, David Bunk, David Hörl, Heinrich Leonhardt, Peter Walter, Till Klecker, Christof Osman. Cristae-dependent quality control of the mitochondrial genome. Science Advances. 2021 Sep 3; 7(36).  View on PubMed
  2. Chang YC, Lamichhane AK, Cai H, Walter PJ, Bennett JE, Kwon-Chung KJ. Moderate levels of 5-fluorocytosine cause the emergence of high frequency resistance in cryptococci. Nat Commun. 2021 06 08; 12(1):3418.  View on PubMed
  3. Michael Schoof, Morgane Boone, Lan Wang, Rosalie Lawrence, Adam Frost, Peter Walter. eIF2B Conformation and Assembly State Regulate the Integrated Stress Response. The FASEB Journal. 2021 May 14; 35(S1).  View on PubMed
  4. Li W, Crotty K, Garrido Ruiz D, Voorhies M, Rivera C, Sil A, Mullins RD, Jacobson MP, Peschek J, Walter P. Protomer alignment modulates specificity of RNA substrate recognition by Ire1. Elife. 2021 Apr 27; 10.  View on PubMed
  5. Schuck S, Prinz WA, Thorn KS, Voss C, Walter P. Correction: Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response. J Cell Biol. 2021 04 05; 220(4).  View on PubMed
  6. Schoof M, Boone M, Wang L, Lawrence R, Frost A, Walter P. eIF2B conformation and assembly state regulate the integrated stress response. Elife. 2021 Mar 10; 10.  View on PubMed
  7. Ramundo S, Asakura Y, Salomé PA, Strenkert D, Boone M, Mackinder LCM, Takafuji K, Dinc E, Rahire M, Crèvecoeur M, Magneschi L, Schaad O, Hippler M, Jonikas MC, Merchant S, Nakai M, Rochaix JD, Walter P. Coexpressed subunits of dual genetic origin define a conserved supercomplex mediating essential protein import into chloroplasts. Proc Natl Acad Sci U S A. 2020 12 22; 117(51):32739-32749.  View on PubMed
  8. Krukowski K, Nolan A, Frias ES, Boone M, Ureta G, Grue K, Paladini MS, Elizarraras E, Delgado L, Bernales S, Walter P, Rosi S. Small molecule cognitive enhancer reverses age-related memory decline in mice. Elife. 2020 12 01; 9.  View on PubMed
  9. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, QCRG Structural Biology Consortium , Walter P, Manglik A. An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike. Science. 2020 12 18; 370(6523):1473-1479.  View on PubMed
  10. Gehlen J, Esser S, Schaffrath K, Johnen S, Walter P, Müller F. Blockade of Retinal Oscillations by Benzodiazepines Improves Efficiency of Electrical Stimulation in the Mouse Model of RP, rd10. Invest Ophthalmol Vis Sci. 2020 11 02; 61(13):37.  View on PubMed
  11. Wang L, Walter P. Msp1/ATAD1 in Protein Quality Control and Regulation of Synaptic Activities. Annu Rev Cell Dev Biol. 2020 10 06; 36:141-164.  View on PubMed
  12. Schoof M, Faust B, Saunders RA, Sangwan S, Rezelj V, Hoppe N, Boone M, Billesbølle CB, Puchades C, Azumaya CM, Kratochvil HT, Zimanyi M, Deshpande I, Liang J, Dickinson S, Nguyen HC, Chio CM, Merz GE, Thompson MC, Diwanji D, Schaefer K, Anand AA, Dobzinski N, Zha BS, Simoneau CR, Leon K, White KM, Chio US, Gupta M, Jin M, Li F, Liu Y, Zhang K, Bulkley D, Sun M, Smith AM, Rizo AN, Moss F, Brilot AF, Pourmal S, Trenker R, Pospiech T, Gupta S, Barsi-Rhyne B, Belyy V, Barile-Hill AW, Nock S, Liu Y, Krogan NJ, Ralston CY, Swaney DL, García-Sastre A, Ott M, Vignuzzi M, QCRG Structural Biology Consortium , Walter P, Manglik A. An ultra-potent synthetic nanobody neutralizes SARS-CoV-2 by locking Spike into an inactive conformation. bioRxiv. 2020 Aug 17.  View on PubMed
  13. 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 11; 5(11):1361-1373.  View on PubMed
  14. 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 IRE1α-dependent RNA decay to modulate the DNA damage response. Nat Commun. 2020 05 14; 11(1):2401.  View on PubMed
  15. Costa-Mattioli M, Walter P. The integrated stress response: From mechanism to disease. Science. 2020 04 24; 368(6489).  View on PubMed
  16. 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. IRE1α Disruption in Triple-Negative Breast Cancer Cooperates with Antiangiogenic Therapy by Reversing ER Stress Adaptation and Remodeling the Tumor Microenvironment. Cancer Res. 2020 06 01; 80(11):2368-2379.  View on PubMed
  17. 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.  View on PubMed
  18. 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.  View on PubMed
  19. 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 06 01; 37(11):1370-1380.  View on PubMed
  20. Wang L, Myasnikov A, Pan X, Walter P. Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction. Elife. 2020 01 30; 9.  View on PubMed

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