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. Yamoah A, Tripathi P, Guo H, Scheve L, Walter P, Johnen S, Müller F, Weis J, Goswami A. Early Alterations of RNA Binding Protein (RBP) Homeostasis and ER Stress-Mediated Autophagy Contributes to Progressive Retinal Degeneration in the rd10 Mouse Model of Retinitis Pigmentosa (RP). Cells. 2023 04 06; 12(7).  View on PubMed
  2. Rosalie Lawrence, Sophie Shoemaker, Aniliese Deal, Lan Wang, Susan Marqusee, Peter Walter. A central helical switch controls integrated stress response signaling via eIF2B conformation and assembly. Biophysical Journal. 2023 Feb 1; 122(3):32a.  View on PubMed
  3. Al-Haddad A, Oberli S, González-Vázquez J, Bucher M, Doumy G, Ho P, Krzywinski J, Lane TJ, Lutman A, Marinelli A, Maxwell TJ, Moeller S, Pratt ST, Ray D, Shepard R, Southworth SH, Vázquez-Mayagoitia Á, Walter P, Young L, Picón A, Bostedt C. Observation of site-selective chemical bond changes via ultrafast chemical shifts. Nat Commun. 2022 Nov 22; 13(1):7170.  View on PubMed
  4. Frias ES, Hoseini MS, Krukowski K, Paladini MS, Grue K, Ureta G, Rienecker KDA, Walter P, Stryker MP, Rosi S. Aberrant cortical spine dynamics after concussive injury are reversed by integrated stress response inhibition. Proc Natl Acad Sci U S A. 2022 10 18; 119(42):e2209427119.  View on PubMed
  5. Belyy V, Zuazo-Gaztelu I, Alamban A, Ashkenazi A, Walter P. Endoplasmic reticulum stress activates human IRE1α through reversible assembly of inactive dimers into small oligomers. Elife. 2022 06 22; 11.  View on PubMed
  6. Wang L, Toutkoushian H, Belyy V, Kokontis CY, Walter P. Conserved structural elements specialize ATAD1 as a membrane protein extraction machine. Elife. 2022 05 12; 11.  View on PubMed
  7. 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 05; 54(5):705-714.  View on PubMed
  8. 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 04 13; 11.  View on PubMed
  9. 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
  10. 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
  11. 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
  12. 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
  13. K. Krukowski, Amber Nolan, Elma S. Frias, Morgane Boone, Gonzalo Ureta, Katherine Grue, Maria-Serena Paladini, Edward Elizarraras, Luz Delgado, Sebastian Bernales, Peter Walter, Susanna Rosi. Small molecule cognitive enhancer reverses age-related memory decline in mice. Brain Behavior and Immunity. 2021 Nov 1; 98:27.  View on PubMed
  14. 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
  15. 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
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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

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