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

  • March 15, 2012 - March 31, 2026 - The integrated stress response in cognitive disorders , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01NS076708
  • July 1, 1983 - April 30, 2024 - Co-translational ER quality control , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM032384
  • September 30, 2012 - July 31, 2016 - Structural Basis of Protein Homeostasis , Principal Investigator . Sponsor: NIH, Sponsor Award ID: U01GM098254
  • September 30, 1996 - June 30, 2016 - Comprehensive Biology: Exploiting the Yeast Genome , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P41RR011823

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, Toutkoushian H, Belyy V, Kokontis CY, Walter P. Conserved structural elements specialize ATAD1 as a membrane protein extraction machine. Elife. 2022 May 12; 11.  View on PubMed
  2. Fauser F, Vilarrasa-Blasi J, Onishi M, Ramundo S, Patena W, Millican M, Osaki J, Philp C, Nemeth M, Salomé PA, Li X, Wakao S, Kim RG, Kaye Y, Grossman AR, Niyogi KK, Merchant SS, Cutler SR, Walter P, Dinneny JR, Jonikas MC, Jinkerson RE. Systematic characterization of gene function in the photosynthetic alga Chlamydomonas reinhardtii. Nat Genet. 2022 May 05.  View on PubMed
  3. Boone M, Wang L, Lawrence RE, Frost A, Walter P, Schoof M. A point mutation in the nucleotide exchange factor eIF2B constitutively activates the integrated stress response by allosteric modulation. Elife. 2022 Apr 13; 11.  View on PubMed
  4. Yildirim Z, Baboo S, Hamid SM, Dogan AE, Tufanli O, Robichaud S, Emerton C, Diedrich JK, Vatandaslar H, Nikolos F, Gu Y, Iwawaki T, Tarling E, Ouimet M, Nelson DL, Yates JR, Walter P, Erbay E. Intercepting IRE1 kinase-FMRP signaling prevents atherosclerosis progression. EMBO Mol Med. 2022 04 07; 14(4):e15344.  View on PubMed
  5. Le Thomas A, Ferri E, Marsters S, Harnoss JM, Lawrence DA, Zuazo-Gaztelu I, Modrusan Z, Chan S, Solon M, Chalouni C, Li W, Koeppen H, Rudolph J, Wang W, Wu TD, Walter P, Ashkenazi A. Decoding non-canonical mRNA decay by the endoplasmic-reticulum stress sensor IRE1α. Nat Commun. 2021 12 15; 12(1):7310.  View on PubMed
  6. Schoof M, Wang L, Cogan JZ, Lawrence RE, Boone M, Wuerth JD, Frost A, Walter P. Viral evasion of the integrated stress response through antagonism of eIF2-P binding to eIF2B. Nat Commun. 2021 12 07; 12(1):7103.  View on PubMed
  7. 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 IRE1α branch of the unfolded protein response. EMBO J. 2021 Nov 02; 40(21):e109149.  View on PubMed
  8. Tran NH, Carter SD, De Mazière A, Ashkenazi A, Klumperman J, Walter P, Jensen GJ. The stress-sensing domain of activated IRE1α forms helical filaments in narrow ER membrane tubes. Science. 2021 Oct; 374(6563):52-57.  View on PubMed
  9. Jakubke C, Roussou R, Maiser A, Schug C, Thoma F, Bunk D, Hörl D, Leonhardt H, Walter P, Klecker T, Osman C. Cristae-dependent quality control of the mitochondrial genome. Sci Adv. 2021 Sep 03; 7(36):eabi8886.  View on PubMed
  10. 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
  11. 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
  12. 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 04 27; 10.  View on PubMed
  13. 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
  14. Schoof M, Boone M, Wang L, Lawrence R, Frost A, Walter P. eIF2B conformation and assembly state regulate the integrated stress response. Elife. 2021 03 10; 10.  View on PubMed
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

Go to UCSF Profiles, powered by CTSI