German-American molecular biologist and biochemist
Peter Walter (born December 5, 1954) is a German-American
molecular biologist and
biochemist . He is currently the Director of the
Bay Area Institute of Science at
Altos Labs and an
emeritus professor at the Department of
Biochemistry and
Biophysics of the
University of California, San Francisco (UCSF).
[2]
[3] He was a
Howard Hughes Medical Institute (HHMI) Investigator until 2022.
Early life and education
Walter was born and raised in
West Berlin in 1954. His parents owned a
pharmacy , and he was drawn to
chemistry at a young age.
[4] He entered the
Free University of Berlin in 1973 to study chemistry, but the rigid way of teaching science did not engage him. Instead, Walter became interested in
biochemistry , which studies the chemistry of
cells .
[4]
[5]
In the last year of his
Vordiplom (equivalent to a
BSc ) in 1976, he went on
exchange to
Vanderbilt University and conducted research under Thomas M. Harris at the Department of Chemistry on the
biosynthetic pathway of
slaframine , a
fungal
alkaloid that is toxic to
cows .
[6] Eventually, Walter completed his
MSc in Vanderbilt in 1977.
[1]
At the encouragement of
Stanford Moore , a biochemistry professor at
Rockefeller University and a
trustee of Vanderbilt, Walter applied for the
PhD programme at Rockefeller.
[6] He was placed on the waiting list, but after an accepted student went to
Harvard University instead, was offered his place in 1977.
[4]
[5] He took his PhD under
Günter Blobel , and obtained the degree in 1981.
[1]
Career
After receiving his PhD, Walter stayed at
Rockefeller University as a
postdoctoral fellow for a year, then became an assistant professor at the Laboratory of
Cell Biology at Rockefeller.
[1]
In 1983, he moved to the Department of
Biochemistry and
Biophysics of the
University of California, San Francisco (UCSF) as an assistant professor. Walter was promoted to
associate professor in 1986 and then
full professor in five years later.
[1] He was chair of the Department of Biochemistry and Biophysics of UCSF between 2001 and 2008.
[7]
Walter became a
Howard Hughes Medical Institute investigator in 1997, and served as the president of the
American Society for Cell Biology in 2016.
[8]
In 2021, there were reports that he would be joining
Altos Labs , a new
biotechnology company which reportedly focuses on
anti-aging research.
[9]
[10] The next year, he retired from UCSF and the Howard Hughes Medical Institute in 2022,
[11]
[12] and joined Altos Labs as the Director of the
Bay Area Institute of Science when the company officially launched.
[13]
[14]
Walter currently sits on the Scientific Advisory Board of the Zentrum für Molekulare Biologie der Universität Heidelberg of
Heidelberg University .
[15]
Walter is a coauthor of the widely used textbook
Molecular Biology of the Cell .
[16]
Research
[1]
[2]
During his PhD at
Günter Blobel 's group, Walter purified a
protein complex required for moving proteins out of the
endoplasmic reticulum (ER)
[17] and showed the complex selectively recognizes newly synthesized
secretory proteins .
[18] He later confirmed the complex is in fact a
nucleoprotein and identified the RNA component essential for the complex's function. He also named the complex
signal recognition particle (SRP).
[19]
By the time Walter joined the
University of California, San Francisco (UCSF), researchers have established a connection between
misfolded
proteins in the ER and increased expression of a protein called
BiP , which is a
chaperone protein that helps other proteins fold correctly. This pathway is termed the
unfolded protein response (UPR). However, how
cells sense misfolded proteins and relays this information to the
cell nucleus to increase the production of UPR-target proteins remains unclear.
[20]
In 1993, working on
baker's yeast , Walter found a gene,
IRE1 , which encodes a
kinase . The IRE1 protein is located across the ER membrane, so a part of it can detect unfolded proteins inside the ER and the other part can
phosphorylate proteins outside of the ER.
[21] The same year,
Kazutoshi Mori , at the time a
postdoctoral fellow at the
University of Texas Southwestern Medical Center , independently made the same discovery.
[22]
Walter and Mori next independently sought the
phosphorylation target of the IRE1 protein. Theoretically, upon phosphorylation, this target will enter the cell nucleus and increase the production of UPR-target proteins. Both of them arrived at the same gene, HAC1 , in 1996.
[23]
[24] This discovery, however, was unexpected as the HAC1 protein is produced only after IRE1 detects unfolded proteins, meaning the protein is not present to be phosphorylated by IRE1.
This difference was mitigated by the finding of Mori and Walter that after IRE1 senses unfolded proteins, it
splices the HAC1 precursor
mRNA , which is
transcribed from the HAC1
gene , resulting in a mature mRNA that is
translated into the HAC1 protein.
[25]
[26] Walter also discovered the phosphorylation target of IRE1, which turned out to be another IRE1 molecule, a process known as
trans-autophosphorylation ,
[27] and also the
enzyme stitching the spliced precursor HAC1 mRNA together.
[28]
In 2013, Walter's group identified a molecule that inhibits the
integrated stress response (ISR). The ISR is the
cell 's response to stresses such as
viral infection ,
ultraviolet light and the accumulation of
unfolded and
misfolded
proteins . ISR activates the
EIF2α protein, reducing most
protein synthesis and increasing the production of some regulatory
molecules .
[29] His group found the inhibitor reversed EIF2α activation, and named it
ISRIB for "integrated stress response inhibitor". Remarkably, they found
mice injected with ISRIB had improved memory.
[30] ISRIB was licensed to
Alphabet subsidiary
Calico in 2015.
[31]
Awards and honors
Personal life
Walter is married to Patricia Caldera-Muñoz,
[53] whom he met in
New York City during his PhD years at
Rockefeller University and when Caldera-Muñoz was a
chemistry PhD student at
New York University .
[5] Before retiring, Caldera-Muñoz worked at the
University of California, San Francisco (UCSF) Science and Health Education Partnership, where she coordinated outreach to local science teachers.
[54]
[55]
Walter was diagnosed with
neck cancer in 2009.
[56]
References
^
a
b
c
d
e
"PETER WALTER Ph.D."
Vanderbilt University
School of Medicine . Archived from
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^
"Peter Walter" .
Altos Labs . Archived from
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^
"Peter Walter, PhD" .
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^
a
b
c Dreifus, Claudia (June 15, 2015).
"Peter Walter's Voyage Into a Microscopic World" .
The New York Times . Archived from
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^
a
b
c
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Shaw Prize . September 24, 2014. Archived from
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^
a
b Davis, Tinsley H. (2006).
"Profile of Peter Walter" .
Proceedings of the National Academy of Sciences . 103 (14): 5259–5261.
Bibcode :
2006PNAS..103.5259D .
doi :
10.1073/pnas.0600257103 .
PMC
1459343 .
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^
"Prof. Peter Walter" . International Institute of Molecular Mechanisms and Machines,
Polish Academy of Sciences . Archived from
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^
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^ Regalado, Antonio (September 4, 2021).
"Meet Altos Labs, Silicon Valley's latest wild bet on living forever" .
MIT Technology Review . Archived from
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"Silicon Valley start-up funded by billionaires hires top 'anti-aging' experts" .
El País . Archived from
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^
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^
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^
"Altos Labs Launches with $3B and a Focus on Reversing Disease, Aging" . Genetic Engineering & Biotechnology News . January 19, 2022. Archived from
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^
"ZMBH – Scientific Advisory Board" .
Heidelberg University . Archived from
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^ Alberts, Bruce; Heald, Rebecca; Johnson, Alexander; Morgan, David; Raff, Martin; Roberts, Keith; Walter, Peter; Wilson, John; Hunt, Tim (2022).
Molecular Biology of the Cell (7 ed.).
W. W. Norton & Company .
ISBN
978-0-393-88482-1 . Archived from
the original on August 28, 2023. Retrieved August 28, 2023 .
^ Walter, Peter;
Blobel, Günter (1980).
"Purification of a membrane-associated protein complex required for protein translocation across the endoplasmic reticulum" . Proceedings of the National Academy of Sciences . 77 (12): 7112–7116.
Bibcode :
1980PNAS...77.7112W .
doi :
10.1073/pnas.77.12.7112 .
PMC
350451 .
PMID
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^ Walter, Peter; Ibrahimi, Ibrahim;
Blobel, Günter (1981).
"Translocation of proteins across the endoplasmic reticulum. I. Signal recognition protein (SRP) binds to in-vitro-assembled polysomes synthesizing secretory protein" (PDF) .
Journal of Cell Biology . 91 (2): 545–550.
doi :
10.1083/jcb.91.2.545 .
PMC
2111968 .
PMID
7309795 . Archived from
the original (PDF) on August 31, 2023. Retrieved August 31, 2023 .
^ Walter, Peter;
Blobel, Günter (1982).
"Signal recognition particle contains a 7S RNA essential for protein translocation across the endoplasmic reticulum" .
Nature . 299 (5885): 691–698.
Bibcode :
1982Natur.299..691W .
doi :
10.1038/299691a0 .
PMID
6181418 .
S2CID
4237513 .
^
Mori, Kazutoshi (2015).
"The unfolded protein response: the dawn of a new field" . Proceedings of the Japan Academy, Series B Physical and Biological Sciences . 91 (9): 469–480.
Bibcode :
2015PJAB...91..469M .
doi :
10.2183/pjab.91.469 .
PMC
4754504 .
PMID
26560836 . Archived from
the original on September 5, 2023. Retrieved September 5, 2023 .
^ Cox, Jeffrey S.; Shamu, Caroline E.; Walter, Peter (1993).
"Transcriptional induction of genes encoding endoplasmic reticulum resident proteins requires a transmembrane protein kinase" .
Cell . 73 (6): 1197–1206.
doi :
10.1016/0092-8674(93)90648-A .
PMID
8513503 .
S2CID
16065404 .
^
Mori, Kazutoshi ; Ma, Wenzhen; Gething, Mary–Jane;
Sambrook, Joseph (1993).
"A transmembrane protein with a cdc2+/CDC28-related kinase activity is required for signaling from the ER to the nucleus" . Cell . 74 (4): 743–756.
doi :
10.1016/0092-8674(93)90521-q .
PMID
8358794 .
S2CID
20732881 . Retrieved September 5, 2023 .
^ Cox, Jeffey S.; Walter, Peter (1996).
"A Novel Mechanism for Regulating Activity of a Transcription Factor That Controls the Unfolded Protein Response" . Cell . 87 (3): 391–404.
doi :
10.1016/s0092-8674(00)81360-4 .
PMID
8898193 .
^
Mori, Kazutoshi ; Kawahara, Tetsushi; Yoshida, Hiderou; Yanagi, Hideki; Yura, Takashi (1996).
"Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway" . Genes to Cells . 1 (9): 803–817.
doi :
10.1046/j.1365-2443.1996.d01-274.x .
PMID
9077435 .
^ Sidrauski, Carmela; Walter, Peter (1997).
"The Transmembrane Kinase Ire1p Is a Site-Specific Endonuclease That Initiates mRNA Splicing in the Unfolded Protein Response" . Cell . 90 (6): 1031–1039.
doi :
10.1016/s0092-8674(00)80369-4 .
PMID
9323131 .
^ Kawahara, Tetsushi; Yanagi, Hideki; Yura, Takashi;
Mori, Kazutoshi (1997).
"Endoplasmic Reticulum Stress-induced mRNA Splicing Permits Synthesis of Transcription Factor Hac1p/Ern4p That Activates the Unfolded Protein Response" .
Molecular Biology of the Cell . 8 (10): 1845–1862.
doi :
10.1091/mbc.8.10.1845 .
PMC
25627 .
PMID
9348528 .
^ Shamu, Caroline E.; Walter, Peter (1996).
"Oligomerization and phosphorylation of the Irelp kinase during intracellular signaling from the endoplasmic reticulum to the nucleus" .
The EMBO Journal . 15 (12): 3028–3039.
doi :
10.1002/j.1460-2075.1996.tb00666.x .
PMC
450244 .
PMID
8670804 .
^ Gonzalez, Tania N.; Sidrauski, Carmela; Dörfler, Silke; Walter, Peter (1999).
"Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway" . The EMBO Journal . 18 (11): 3119–3132.
doi :
10.1093/emboj/18.11.3119 .
PMC
1171393 .
PMID
10357823 . Archived from
the original on September 7, 2023. Retrieved September 7, 2023 .
^ Pakos-Zebrucka, Karolina; Koryga, Izabela; Mnich, Katarzyna; Ljujic, Mila; Samali, Afshin; Gorman, Adrienne M. (2016).
"The integrated stress response" .
EMBO Reports . 17 (10): 1374–1395.
doi :
10.15252/embr.201642195 .
PMC
5048378 .
PMID
27629041 .
^ Sidrauski, Carmela; Acosta-Alvear, Diego; Khoutorsky, Arkady; Vedantham, Punitha; Hearn, Brian R.; Li, Han; Gamache, Karine; Gallagher, Ciara M.; Ang, Kenny K.-H.; Wilson, Chris; Okreglak, Voytek; Ashkenazi, Avi; Hann, Byron; Nader, Karim; Arkin, Michelle R.; Renslo, Adam R.; Sonenberg, Nahum; Walter, Peter (2013).
"Pharmacological brake-release of mRNA translation enhances cognitive memory" .
eLife . 2 : e00498.
doi :
10.7554/eLife.00498 .
PMC
3667625 .
PMID
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^ Piore, Adam (August 25, 2021).
"The miracle molecule that could treat brain injuries and boost your fading memory" . MIT Technology Review . Archived from
the original on September 2, 2023. Retrieved September 2, 2023 .
^ Fambroug, Douglas M. (2006).
"Searle Scholars Program: Selection and Evaluation of Searle Scholars National Academies of Sciences, Engineering, and Medicine" . Enhancing Philanthropy's Support of Biomedical Scientists: Proceedings of a Workshop on Evaluation National Academies of Sciences, Engineering, and Medicine .
National Academies Press . pp. 43–51.
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^
"Eli Lilly Award in Biological Chemistry" (PDF) . Division of Biological Chemistry,
American Chemical Society . Archived from
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^
"Fellows Database" .
Alfred P. Sloan Foundation . Archived from
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^
"Peter Walter" .
American Academy of Arts and Sciences . Archived from
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^
"Peter Walter" .
National Academy of Sciences . Archived from
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^
"Peter Walter" .
European Molecular Biology Organization . Archived from
the original on May 31, 2023. Retrieved May 31, 2023 .
^
"The Wiley Prize in Biomedical Sciences" . Wiley Foundation. Retrieved August 29, 2023 .
^
"Peter Walter" .
German National Academy of Sciences Leopoldina . Archived from
the original on April 19, 2023. Retrieved April 19, 2023 .
^
"Peter Walter" .
Gairdner Foundation . Archived from
the original on August 29, 2023. Retrieved August 29, 2023 .
^
"E.B. Wilson Medal" . American Society for Cell Biology. Archived from
the original on August 30, 2023. Retrieved August 30, 2023 .
^
"Otto-Warburg-Medaille" . German Society for Biochemistry and Molecular Biology. Archived from
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^
"Prize Winner of the Paul Ehrlich and Ludwig Darmstaedter Prize 2012" .
Goethe University Frankfurt . Archived from
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^
"Laureates 1976 to 2022" . Ernst Jung Foundation. Archived from
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^
"The unfolded protein response in health and disease" .
Mendel Lectures . Archived from
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^
"The 2014 Prize in Life Science & Medicine" . Shaw Prize. Archived from
the original on August 23, 2023. Retrieved August 23, 2023 .
^
"2014 Albert Lasker Basic Medical Research Award" .
Lasker Award . Archived from
the original on August 30, 2023. Retrieved August 30, 2023 .
^
"Peter Walter" .
Vilcek Foundation . Archived from
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^
"Fellows List" .
National Academy of Inventors . Archived from
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^
"Dr. Peter Walter" .
National Academy of Medicine . Archived from
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^
"Peter Walter" .
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^
BBVA Foundation Frontiers of Knowledge Award 2023
^ Kim, Leland (September 19, 2014).
"Peter Walter: 'This Honor Really Belongs to All of Us' " . University of California, San Francisco. Archived from
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^ Landhuis, Esther (2015).
"Harnessing Serendipity" . HHMI Bulletin . Vol. 28, no. 3. pp. 18–23. Archived from
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^ Kaarlela, Corinna (May 31, 2006).
"New council promotes partnerships between UCSF and community" . University of California, San Francisco. Archived from
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^ McFarling, Usha Lee (September 28, 2016).
"Peter Walter just won the Breakthrough Prize. His work? Trying to heal human brains" .
Stat . Archived from
the original on September 1, 2023. Retrieved September 1, 2023 .
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