German-American biochemist
Thomas Christian Sudhof
(
German pronunciation:
[?toːmas
?zyːt?hoːf]
ⓘ
; born December 22, 1955),
ForMemRS
, is a German-American
biochemist
known for his study of
synaptic transmission
. Currently, he is a professor in the school of medicine in the department of
molecular
and
cellular physiology
, and by courtesy in neurology, and in psychiatry and behavioral sciences at
Stanford University
.
[2]
[5]
Sudhof,
James Rothman
and
Randy Schekman
are the 2013
Nobel Prize in Physiology or Medicine
laureates for their work on
vesicle
trafficking.
[6]
Early life and education
[
edit
]
A
German native
, Sudhof was born in
Gottingen
in 1955. He spent his childhood in Gottingen and
Hannover
. He studied music in his youth, specifically the bassoon, and has credited his
bassoon
instructor, Herbert Tauscher, as his "most influential teacher".
[7]
He was a graduate from the
Hannover Waldorf School
in 1975. Sudhof studied medicine at the
RWTH Aachen University
,
Harvard University
, and then the
University of Gottingen
. In Gottingen Sudhof worked on his doctoral thesis, in which he described the structure and function of
chromaffin cells
, at the
Max Planck Institute for Biophysical Chemistry
in the lab of
Victor P. Whittaker
. In 1982, he received his
MD
in medical science (Dr.med.) from the
University of Gottingen
.
[8]
Career and research
[
edit
]
After a brief
postdoctoral fellowship
in Whittaker's lab, Sudhof moved to the United States in 1983, where he began postdoctoral training in the department of
molecular genetics
at the University of Texas Health Science Center (now the
UT Southwestern Medical Center
) in
Dallas
, Texas, under the supervision of
Michael Stuart Brown
and
Joseph L. Goldstein
.
During his
postdoctoral research
fellowship
, Sudhof worked to describe the role of the
LDL receptor
in
cholesterol
metabolism, for which Brown and Goldstein were awarded the
Nobel Prize in Physiology or Medicine
in 1985. Sudhof finished his postdoctoral training in 1986 and was elected to be an investigator of the
Howard Hughes Medical Institute
. He then established his own laboratory at UT Southwestern Medical Center where he focused on the molecular and cellular neurosciences centered on synapses for over 20 years.
In 2008, Sudhof moved to
Stanford University
and is currently the Avram Goldstein Professor in the
School of Medicine
as well as a Professor of Molecular & Cellular
Physiology
,
Psychiatry
, and
Neurology
.
Sudhof laid the foundations for his scientific career studying the synapse early while studying the mechanisms of
neurotransmitter
dependent hormone release from neuroendocrine cells for his doctoral thesis at the
Max Planck Institute for Biophysical Chemistry
. Sudhof described the structure and function of
chromaffin cells
which are responsible for the release of
epinephrine
,
norepinephrine
and
endorphins
from the
medulla
of the
adrenal gland
. Innervated by
sympathetic nervous system
, chromaffin cells are important in the initiation of the
fight-or-flight response
of animals when exposed to threatening stimuli.
After completing his thesis in 1983, Sudhof moved to
UT Southwestern Medical Center
for his postdoctoral training where he began researching in the department of
molecular genetics
under the supervision of
Joseph L. Goldstein
and
Michael Stuart Brown
. While a postdoctoral fellow, Sudhof cloned the gene for the
low-density lipoprotein
receptor and, soon after, was able to explain its transcriptional regulation by cholesterol. When LDL receptors, found concentrated in the liver, bind specific free blood cholesterol, low-density lipoprotein, they are internalized and recycled removing the cholesterol from circulation. This process is a primary source of blood cholesterol regulation and variations in its efficiency were shown to be present in
familial hypercholesterolemia
. As a result of the discovery, LDL receptor function had also elucidated the principle of
receptor-mediated endocytosis
?a now universally understood process in cell biology. Goldstein and Brown were awarded the Nobel Prize in Physiology or Medicine for the discovery in 1985.
After finishing postdoctoral training, Sudhof started his own laboratory at UT Southwestern in 1986. Briefly continuing work with Goldstein and Brown, Sudhof helped identify a DNA element in the LDL gene that produced
sterol
mediated end-product repression when inserted in a viral promoter. This domain, known as a sterol regulatory sequence, directly participates in the regulation of sterol biosynthesis. Sterols are a major class of biomolecule and critical for life. Important sterols in humans include
cholesterol
and
steroid hormones
. Discovery of sterol regulatory elements and LDL receptor function led to the subsequent development of
statin
derived cholesterol medications such as
atorvastatin
(Lipitor)?the top-selling branded pharmaceutical drug in the world in 2008.
Sudhof started his independent research career in neuroscience since 1986 and open the field of molecular neuroscience for synaptic transmission especially from the presynaptic nerve terminal perspective. Until Sudhof began his work, majority of neuroscience research was aimed at the postsynaptic neuron and its role in learning and memory. Indeed, Thomas Sudhof is credited with discovering much of the machinery mediating neurotransmitter release and presynaptic plasticity in his 21 years at UT Southwestern. Sudhof began with the discovery of
synaptotagmins
and their role in neurotransmitter release from the presynaptic neuron. Synaptotagmin, a transmembrane protein found in neurosecretory vesicles, functions as a calcium sensor triggering vesicle fusion and neurotransmitter release. Stimulation of a neuron results in an increase in intracellular calcium concentration. After binding calcium ion to a region in its cytosolic domain, vesicular synaptotagmin promotes quick or slow neurotransmitter release from the presynaptic neuron via interaction with regulatory and fusion related proteins such as members of the
SNARE
complex. Sudhof also discovered RIMs and Muncs (most notably Munc13 and Munc18), soluble proteins which aid in the fusion of neurotransmitter vesicles to the nerve cell membrane and play an important role in synaptic plasticity. In addition, Sudhof's research uncovered the role of many other proteins facilitating vesicle binding, fusion, and resultant neurotransmitter release from the presynaptic neuron, including members of the SNARE complex:
synaptobrevin
, in the vesicular membrane,
syntaxin
, in the cell membrane, and
SNAP25
, which is tethered to the cytosolic side of the cell membrane via cysteine-linked palmitoyl chains and holds the complex of four helices together. Sudhof was also responsible for elucidating the action of tetanus and botulinum toxins, which selectively cleave synaptobrevin and SNAP25, respectively, inhibiting vesicle fusion with the presynaptic membrane.
A second influential contribution of Sudhof is on synapse formation and specifications. Sudhof discovered a number of key molecules in this process such as
neurexins
, present on presynaptic neurons, and
neuroligins
, present on postsynaptic neurons, that come together to form a physical protein bridge across the synapse. The diversity in types of neurexins and neuroligins allows for a variety of unique binding opportunities between neurons and impart a specificity to synaptic connections. Additionally he also discovered or elucidated the important functions of SynCAM, Latrophilins etc. in synapse formation. In additional studies, Sudhof identified mutations in these proteins as a factor in inherited
autism
. Sudhof is striving to elucidate the mechanism by which neurexins and neuroligins locate each other to form the synapse, their transcriptional regulation, and control of their variability.
Sudhof currently continues his work on synapse formation, maintenance as well as synaptic releases in his laboratory at Stanford University. Additionally, together with
Marius Wernig
at Stanford University, Sudhof developed induced neuronal cell technology where they can use human neuronal cells derived from patients or genetically engineered with defined mutations that linked to neuropsychiatric disorders or neurodevelopmental disorders. Sudhof's research has not only given the scientific community a great understanding of the processes underlying synaptic transmission and synapse formation, but has also advanced medical knowledge of mechanisms behind poorly understood diseases such as Alzheimer's, Schizophrenia, and Autism. He is currently working with a diverse group of researchers at the
Howard Hughes Medical Institute
to develop mouse models for mutants of synaptic genes. The project aims to drastically advance our understanding of neurological disorders. He also serves on the Research Consortium of
Cure Alzheimer's Fund
.
Sudhof recently retracted a 2023 paper from Proceedings of the National Academy of Science after complaints sent to the journal due to "discrepancies between the raw data and the published data".
[9]
Science and policy
[
edit
]
Sudhof recently
[
when?
]
also engages in scientific ethics as exemplified by his recent work at
PLOS Biology
Truth in Science Publishing: A personal Perspective
[10]
and various interviews including his discussion about music, policy and medicine with
The Lancet
.
[7]
In 2017, he published an article in
The Washington Post
[11]
on basic research vs. drug development.
Other activities
[
edit
]
In 2023, Sudhof was appointed by
United Nations Secretary General
Antonio Guterres
to the United Nations' Scientific Advisory Board.
[12]
Corporate board memberships include:
- Neurocentria, member of the scientific advisory board (since 2023)
[13]
- Sanofi
, independent member of the board of directors (since 2016)
[14]
Awards and honors
[
edit
]
Personal life
[
edit
]
Sudhof is married
[
when?
]
to
Lu Chen
, a professor of neurosurgery and of psychiatry and behavioral sciences at Stanford University. The couple have three children.
[
citation needed
]
Sudhof has four more children from his previous marriage with Annette Sudhof.
[18]
References
[
edit
]
- ^
a
b
Anon (2017).
"Professor Thomas Sudhof ForMemRS"
.
royalsociety.org
.
Royal Society
.
- ^
a
b
"CAP - Thomas Sudhof"
. Med.stanford.edu. June 20, 2008
. Retrieved
October 7,
2013
.
- ^
"Ist der Nobelpreistrager Sudhof uberhaupt Deutscher?"
. Focus
. Retrieved
October 7,
2013
.
- ^
Medizinnobelpreistrager Thomas Sudhof ?Ich habe wieder einen deutschen Pass“, Berliner Zeitung, 27 January 2014 (German)
- ^
Vierbuchen, Thomas; Ostermeier, Austin; Pang, Zhiping P.; Kokubu, Yuko; Sudhof, Thomas C.; Wernig, Marius (2010).
"Direct conversion of fibroblasts to functional neurons by defined factors"
.
Nature
.
463
(7284): 1035?1041.
Bibcode
:
2010Natur.463.1035V
.
doi
:
10.1038/nature08797
.
PMC
2829121
.
PMID
20107439
.
- ^
"The Nobel Prize in Physiology or Medicine 2013"
. Nobel Foundation
. Retrieved
October 7,
2013
.
- ^
a
b
Anon (2010).
"Tom Sudhof"
.
The Lancet
.
376
(9739): 409.
doi
:
10.1016/S0140-6736(10)61210-X
.
ISSN
0140-6736
.
PMID
20692517
.
S2CID
54353897
.
- ^
Sudhof, Thomas Christian (1992).
Die biophysikalische Struktur der chromaffinen Granula im Lichte ihres Osmometerverhaltens und ihrer osmotischen Lyse
(MD thesis). University of Gottingen.
OCLC
916944001
.
- ^
www
.thetransmitter
.org
/retraction
/nobel-prize-winner-thomas-sudhof-retracts-study
/
- ^
Sudhof, Thomas C. (August 26, 2016).
"Truth in Science Publishing: A Personal Perspective"
.
PLOS Biology
.
14
(8): e1002547.
doi
:
10.1371/journal.pbio.1002547
.
ISSN
1545-7885
.
PMC
5001634
.
PMID
27564858
.
- ^
Sudhof, Thomas (2017).
"Too many medical trials are moonshots in the dark"
.
washingtonpost.com
.
- ^
UN Secretary-General Creates Scientific Advisory Board for Independent Advice on Breakthroughs in Science and Technology
United Nations
, press release of 3 August 2023.
- ^
Neurocentria announces Dr. Thomas Sudhof to join the Scientific Advisory Board
Neurocentria, press release of 12 January 2023.
- ^
Board of Directors
Sanofi
.
- ^
"Prizewinners of the Feldberg Foundation"
. Feldberg Foundation
. Retrieved
April 26,
2018
.
- ^
"MetLife Foundation Awards for Medical Research in Alzheimer's Disease"
(PDF)
. Archived from
the original
(PDF)
on October 13, 2018.
- ^
"Golden Plate Awardees of the American Academy of Achievement"
.
www.achievement.org
.
American Academy of Achievement
.
- ^
"Thomas Sudhof Nobel Prize bio note"
(PDF)
(Press release).
External links
[
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]
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1901?1925
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1926?1950
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1976?2000
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2001?present
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Astrophysics
|
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,
Donald Lynden-Bell
(2008)
- Jerry E. Nelson
,
Raymond N. Wilson
,
Roger Angel
(2010)
- David C. Jewitt
,
Jane Luu
,
Michael E. Brown
(2012)
- Alan Guth
,
Andrei Linde
,
Alexei Starobinsky
(2014)
- Ronald Drever
,
Kip Thorne
,
Rainer Weiss
(2016)
- Ewine van Dishoeck
(2018)
- Andrew Fabian
(2020)
- Roger Ulrich
,
Jørgen Christensen-Dalsgaard
,
Conny Aerts
(2022)
|
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Nanoscience
|
- Louis E. Brus
,
Sumio Iijima
(2008)
- Donald Eigler
,
Nadrian Seeman
(2010)
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(2012)
- Thomas Ebbesen
,
Stefan Hell
,
John Pendry
(2014)
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,
Christoph Gerber
,
Calvin Quate
(2016)
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,
Jennifer Doudna
,
Virginijus ?ik?nys
(2018)
- Harald Rose
,
Maximilian Haider
,
Knut Urban
,
Ondrej Krivanek
(2020)
- Jacob Sagiv
,
Ralph G. Nuzzo
,
David L. Allara
,
George M. Whitesides
(2022)
|
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Neuroscience
|
- Sten Grillner
,
Thomas Jessell
,
Pasko Rakic
(2008)
- Richard Scheller
,
Thomas C. Sudhof
,
James Rothman
(2010)
- Cornelia Bargmann
,
Winfried Denk
,
Ann Graybiel
(2012)
- Brenda Milner
,
John O'Keefe
,
Marcus Raichle
(2014)
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,
Michael Merzenich
,
Carla J. Shatz
(2016)
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,
Robert Fettiplace
,
Christine Petit
(2018)
- David Julius
,
Ardem Patapoutian
(2020)
- Jean-Louis Mandel
,
Harry T. Orr
,
Christopher A. Walsh
,
Huda Zoghbi
(2022)
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International
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