Peter Walter

Peter Walter (born December 5, 1954) is a German-

American molecular biologist and biochemist. He is Peter Walter
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.

Walter in 2021
Early life and education
Born December 5, 1954
Walter was born and raised in West Berlin in 1954. His West Berlin
parents owned a pharmacy, and he was drawn to Education Free University of Berlin
chemistry at a young age.[4] He entered the Free (Vordiplom)
University of Berlin in 1973 to study chemistry, but the Vanderbilt University (MS)
rigid way of teaching science did not engage him. Rockefeller University (PhD)[1]
Instead, Walter became interested in biochemistry, Known for Signal recognition particle
which studies the chemistry of cells.[4][5] Unfolded protein response
Awards Eli Lilly Award in Biological
In the last year of his Vordiplom (equivalent to a BSc)
Chemistry
in 1976, he went on exchange to Vanderbilt University
Wiley Prize in Biomedical
and conducted research under Thomas M. Harris at the
Science
Department of Chemistry on the biosynthetic pathway
Gairdner Foundation International
of slaframine, a fungal alkaloid that is toxic to cows.[6]
Award
Eventually, Walter completed his M.S. at Vanderbilt in
E.B. Wilson Medal
1977.[1]
Otto Warburg Medal
At the encouragement of Stanford Moore, a Paul Ehrlich and Ludwig
biochemistry professor at Rockefeller University and a Darmstaedter Prize
Ernst Jung Prize
trustee of Vanderbilt, Walter applied for the PhD
Mendel Lectures
programme at Rockefeller.[6] He was placed on the
Shaw Prize in Life Science and
waiting list, but after an accepted student went to
Medicine
Harvard University instead, was offered his place in
Albert Lasker Award for Basic
1977.[4][5] He took his PhD under Günter Blobel, and
Medical Research
obtained the degree in 1981.[1]
Breakthrough Prize in Life
Sciences

Career Scientific career

Fields Molecular biology
Biochemistry
After receiving his PhD, Walter stayed at Rockefeller Institutions Rockefeller University
University as a postdoctoral fellow for a year, then University of California, San
became an assistant professor at the Laboratory of Cell Francisco
Biology at Rockefeller.[1] Howard Hughes Medical Institute
Thesis Purification and characterization
In 1983, he moved to the Department of Biochemistry
of an 11S protein complex
and Biophysics of the University of California, San
required for the translocation of
Francisco (UCSF) as an assistant professor. Walter was
secretory proteins across the
promoted to associate professor in 1986 and then full
membrane of the endoplasmic
professor in five years later.[1] He was chair of the
reticulum (https://rockefeller-prim
Department of Biochemistry and Biophysics of UCSF o.hosted.exlibrisgroup.com/perm
between 2001 and 2008.[7] alink/f/ji7ros/01RU_ALMA212180
3780004157) (1981)
Walter became a Howard Hughes Medical Institute
investigator in 1997, and served as the president of the Doctoral Günter Blobel
American Society for Cell Biology in 2016.[8] advisor

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] (https://www.hhmi.org/bulletin/fall-2015/harnessing-serendipity) [2] (https://laskerfoundation.org/win
ners/unfolded-protein-response/)

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

1983 - Searle Scholar[32]
1988 - Eli Lilly Award in Biological Chemistry[33]
1989 - Sloan Research Fellowship[34]
2002 - Member of the American Academy of Arts and Sciences[35]
2004 - Member of the National Academy of Sciences[36]
2004 - Associate Member of the European Molecular Biology Organization[37]
2005 - Wiley Prize in Biomedical Science[38]
2006 - Member of the German National Academy of Sciences Leopoldina[39]
2009 - Gairdner Foundation International Award[40]
2009 - E.B. Wilson Medal[41]
2011 - Otto Warburg Medal[42]
2012 - Paul Ehrlich and Ludwig Darmstaedter Prize[43]
2012 - Ernst Jung Prize[44]
2013 - Mendel Lectures[45]
2014 - Shaw Prize in Life Science and Medicine[46]
2014 - Albert Lasker Award for Basic Medical Research[47]
2015 - Vilcek Prize in Biomedical Science[48]
2017 - Fellow of the National Academy of Inventors[49]
2018 - Member of the National Academy of Medicine[50]
 2018 - Breakthrough Prize in Life Sciences[51]
2023 - BBVA Foundation Frontiers of Knowledge Award[52]

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]

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External links

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