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
  • September 24, 2004 - August 31, 2015 - Membrane Protein Expression Center , Co-Investigator . Sponsor: NIH, Sponsor Award ID: P50GM073210
  • June 1, 2007 - May 31, 2008 - Stress Proteins in Growth, Development &Disease 2007Gordon Research Conference , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13AG030760
  • September 30, 2003 - August 31, 2007 - QUATTRO ALLIANCE FOR SCIENCE AND LANGUAGE INTEGRATION , Co-Principal Investigator . Sponsor: NIH, Sponsor Award ID: R25RR018504
  • July 1, 1983 - June 30, 2003 - MECHANISM OF PROTEIN TRANSLOCATION ACROSS MEMBRANES , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R37GM032384
  • July 1, 2001 - June 30, 2002 - Molecular Cell Biology Gordon Conference , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R13CA091820
  • December 1, 1986 - November 30, 1999 - PROTEIN TRANSLOCATION IN YEAST , Principal Investigator . Sponsor: NIH, Sponsor Award ID: R01GM037485

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. Strong R, Nelson JF, Bogue MA, Colca JR, Denzel M, Diaz V, Finck BN, Gladyshev VN, Horvath S, Jiang N, Keller T, Kletzien RF, Korstanje R, Kumar N, Leeuwenburgh C, Fernandez E, Galecki A, Ginsburg B, Han M, Kaczorowski C, Leiser S, Lopez-Cruzan M, Raj K, Reifsnyder PC, Rosenthal NA, Rosi S, Shindyapina A, Stacpoole P, Salmon AB, Tyshkovskiy A, Walter P, Whitman M, Miller RA, Harrison DE Extension of lifespan by epicatechin, halofuginone and mitoglitazone in male but not female genetically heterogeneous mice.  View on PubMed
  2. Richard B, Boll R, Banerjee S, Schäfer JM, Jurek Z, Kastirke G, Fehre K, Schöffler MS, Anders N, Baumann TM, Eckart S, Erk B, De Fanis A, Dörner R, Grundmann S, Grychtol P, Hofmann M, Ilchen M, Kircher M, Kubicek K, Kunitski M, Li X, Mazza T, Meister S, Melzer N, Montano J, Music V, Ovcharenko Y, Passow C, Pier A, Rennhack N, Rist J, Rivas DE, Rolles D, Schlichting I, Schmidt LPH, Schmidt P, Trabert D, Trinter F, Wagner R, Walter P, Ziolkowski P, Rudenko A, Meyer M, Santra R, Inhester L, Jahnke T Imaging collective quantum fluctuations of the structure of a complex molecule.  View on PubMed
  3. Zhang J, Bing Z, Marie C, Izsvák Z, Müller F, Thumann G, Walter P, Johnen S Effect of degeneration stage on non-viral tissue transfection of rd10 retina ex vivo.  View on PubMed
  4. Schaffrath K, Ingensiep C, Müller F, Walter P, Johnen S Effects of taurine, brimonidine and betaxolol on oscillation modulation and stimulation efficiency in degenerated rd10 mouse retinas.  View on PubMed
  5. Pharkjaksu S, Cai H, Walter PJ, Chang YC, Kwon-Chung KJ Elevated UDP-glucuronic acid levels mend drug resistance and stress responses via a protease and a transporter in Cryptococcus gattii.  View on PubMed
  6. Reineke LC, Zhu PJ, Dalwadi U, Dooling SW, Liu Y, Wang IC, Young-Baird S, Okoh J, Kuncha SK, Zhou H, Kannan A, Park H, Debeaubien NA, Croll T, Lee DJ, Arthur C, Dever TE, Walter P, Chen J, Frost A, Costa-Mattioli M Harnessing the Evolution of Proteostasis Networks to Reverse Cognitive Dysfunction.  View on PubMed
  7. Kakeshpour T, Louis JM, Walter PJ, Bax A Chemical Analysis of Deep-Lung Fluid Derived from Exhaled Breath Particles.  View on PubMed
  8. Diao S, Zou JY, Wang S, Ghaddar N, Chan JE, Kim H, Poulain N, Koumenis C, Hatzoglou M, Walter P, Sonenberg N, Le Quesne J, Tammela T, Koromilas AE. Lineage plasticity of the integrated stress response is a hallmark of cancer evolution. bioRxiv. 2025 Feb 13.  View on PubMed
  9. Acosta-Alvear D, Harnoss JM, Walter P, Ashkenazi A. Homeostasis control in health and disease by the unfolded protein response. Nat Rev Mol Cell Biol. 2025 Mar; 26(3):193-212.  View on PubMed
  10. Chi DL, Lewis FM, Weinstein P, Mancl L, Milgrom P, Edwards T, Coldwell S, O'Brien D, Bersamin A, Hopkins S, Orr E, Rivera P, Lenaker D, Sylvetsky A, Gittelsohn J, Walter P, Randall CL, Wiseman D, Dock A, Ko A, Orack J, Nemawarkar D, Panchal S, Soper J, Hill CM, Kerr D, Nguyen DP, Chen CY, MacLachlan E Healthy Drinks, Healthy Teeth - Ciunerkaq Tanqigtuq (The Future is Bright): A study protocol for a community-based, non-randomized sociobehavioral trial to reduce added sugar intake in Alaska Native Yup'ik children in the Yukon-Kuskokwim Delta.  View on PubMed
  11. Mukherjee MM, Biesbrock D, Abramowitz LK, Pavan M, Kumar B, Walter PJ, Azadi P, Jacobson KA, Hanover JA. Selective bioorthogonal probe for N-glycan hybrid structures. Nat Chem Biol. 2025 May; 21(5):681-692.  View on PubMed
  12. Schoof M, Boone M, Wang L, Lawrence R, Frost A, Walter P. Correction: eIF2B conformation and assembly state regulate the integrated stress response. Elife. 2024 Oct 03; 13.  View on PubMed
  13. Driver T, Mountney M, Wang J, Ortmann L, Al-Haddad A, Berrah N, Bostedt C, Champenois EG, DiMauro LF, Duris J, Garratt D, Glownia JM, Guo Z, Haxton D, Isele E, Ivanov I, Ji J, Kamalov A, Li S, Lin MF, Marangos JP, Obaid R, O'Neal JT, Rosenberger P, Shivaram NH, Wang AL, Walter P, Wolf TJA, Wörner HJ, Zhang Z, Bucksbaum PH, Kling MF, Landsman AS, Lucchese RR, Emmanouilidou A, Marinelli A, Cryan JP Attosecond delays in X-ray molecular ionization.  View on PubMed
  14. Piknova B, Park JW, Tunau-Spencer KJ, Jenkins A, Hellinga DG, Walter PJ, Cai H, Schechter AN Skeletal Muscle, Skin, and Bone as Three Major Nitrate Reservoirs in Mammals: Chemiluminescence and 15N-Tracer Studies in Yorkshire Pigs.  View on PubMed
  15. Sylvetsky AC, Kuttamperoor JT, Langevin B, Murphy J, Arcaro KF, Smolyak S, Walter PJ, Cai H, Daines DH, van den Anker JN, Gopalakrishnan M Intergenerational transmission of sucralose and acesulfame-potassium from mothers to their infants via human milk: a pharmacokinetic study.  View on PubMed
  16. Piacentino D, Vizioli C, Barb JJ, Grant-Beurmann S, Bouhlal S, Battista JT, Jennings O, Lee MR, Schwandt ML, Walter P, Henderson WA, Chen K, Turner S, Yang S, Fraser CM, Farinelli LA, Farokhnia M, Leggio L Gut microbial diversity and functional characterization in people with alcohol use disorder: A case-control study.  View on PubMed
  17. Dietsche KB, Magge SN, Dixon SA, Davis FS, Krenek A, Chowdhury A, Mabundo L, Stagliano M, Courville AB, Yang S, Turner S, Cai H, Kasturi K, Sherman AS, Ha J, Shouppe E, Walter M, Walter PJ, Chen KY, Brychta RJ, Peer C, Zeng Y, Figg W, Cogen F, Estrada DE, Chacko S, Chung ST Glycemia and Gluconeogenesis With Metformin and Liraglutide: A Randomized Trial in Youth-onset Type 2 Diabetes.  View on PubMed
  18. Park JW, Piknova B, Tunau-Spencer KJ, Thomas SM, Cai H, Walter PJ, Jenkins A, Hellinga D, Parver LM, Schechter AN Dietary Nitrate Metabolism in Porcine Ocular Tissues Determined Using 15N-Labeled Sodium Nitrate Supplementation.  View on PubMed
  19. Coulson RL, Frattini V, Moyer CE, Hodges J, Walter P, Mourrain P, Zuo Y, Wang GX Translational modulator ISRIB alleviates synaptic and behavioral phenotypes in Fragile X syndrome.  View on PubMed
  20. Lawrence RE, Shoemaker SR, Deal A, Sangwan S, Anand AA, Wang L, Marqusee S, Walter P. A helical fulcrum in eIF2B coordinates allosteric regulation of stress signaling. Nat Chem Biol. 2024 04; 20(4):422-431.  View on PubMed

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