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. Schuck S, Prinz WA, Thorn KS, Voss C, Walter P Correction: Membrane expansion alleviates endoplasmic reticulum stress independently of the unfolded protein response.  View on PubMed
  2. eIF2B conformation and assembly state regulates the integrated stress response.  View on PubMed
  3. 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.  View on PubMed
  4. 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.  View on PubMed
  5. 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, Walter P, Manglik A An ultrapotent synthetic nanobody neutralizes SARS-CoV-2 by stabilizing inactive Spike.  View on PubMed
  6. Wang L, Walter P Msp1/ATAD1 in Protein Quality Control and Regulation of Synaptic Activities.  View on PubMed
  7. 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.  View on PubMed
  8. 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.  View on PubMed
  9. 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.  View on PubMed
  10. Costa-Mattioli M, Walter P The integrated stress response: From mechanism to disease.  View on PubMed
  11. 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.  View on PubMed
  12. Weihan Li, Kelly Crotty, Diego Garrido Ruiz, Jirka Peschek, Peter Walter Regulating ER protein homeostasis by differentially processing mRNAs.  View on PubMed
  13. 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.  View on PubMed
  14. 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.  View on PubMed
  15. Wang L, Myasnikov A, Pan X, Walter P Structure of the AAA protein Msp1 reveals mechanism of mislocalized membrane protein extraction.  View on PubMed
  16. Lam M, Marsters SA, Ashkenazi A, Walter P Misfolded proteins bind and activate death receptor 5 to trigger apoptosis during unresolved endoplasmic reticulum stress.  View on PubMed
  17. Belyy V, Tran NH, Walter P Quantitative microscopy reveals dynamics and fate of clustered IRE1a.  View on PubMed
  18. 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.  View on PubMed
  19. Anand AA, Walter P Structural insights into ISRIB, a memory-enhancing inhibitor of the integrated stress response.  View on PubMed
  20. 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.  View on PubMed

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