Thomas Christian Südhof (; born December 22, 1955),

ForMemRS Fellowship of the Royal Society (FRS, ForMemRS and HonFRS) is an award granted by the Fellows of the Royal Society of London to individuals who have made a "substantial contribution to the improvement of natural science, natural knowledge, incl ...

, is a German-American

biochemist Biochemists are scientists who are trained in biochemistry. They study chemical processes and chemical transformations in living organisms. Biochemists study DNA, proteins and Cell (biology), cell parts. The word "biochemist" is a portmanteau of ...

known for his study of

synaptic transmission Neurotransmission (Latin: ''transmissio'' "passage, crossing" from ''transmittere'' "send, let through") is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron) ...

. Currently, he is a professor in the school of medicine in the department of

molecular A molecule is a group of two or more atoms that are held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemistry, ...

and cellular physiology, and by courtesy in neurology, and in psychiatry and behavioral sciences at

Stanford University Leland Stanford Junior University, commonly referred to as Stanford University, is a Private university, private research university in Stanford, California, United States. It was founded in 1885 by railroad magnate Leland Stanford (the eighth ...

. Südhof, James Rothman and Randy Schekman are the 2013

Nobel Prize in Physiology or Medicine The Nobel Prize in Physiology or Medicine () is awarded yearly by the Nobel Assembly at the Karolinska Institute for outstanding discoveries in physiology or medicine. The Nobel Prize is not a single prize, but five separate prizes that, acco ...

laureates for their work on vesicle trafficking. Südhof retracte
Lin et al. 2023
research paper published in PNAS from his lab due to falsified data, and since mid-2022, PubPeer commenters including Elisabeth Bik have flagged 46 of Südhof’s papers, which explore how neurons communicate across synapses.

Early life and education

A German native, Südhof was born in

Göttingen Göttingen (, ; ; ) is a college town, university city in Lower Saxony, central Germany, the Capital (political), capital of Göttingen (district), the eponymous district. The River Leine runs through it. According to the 2022 German census, t ...

in 1955. He spent his childhood in Göttingen and

Hannover Hanover ( ; ; ) is the capital and largest city of the States of Germany, German state of Lower Saxony. Its population of 535,932 (2021) makes it the List of cities in Germany by population, 13th-largest city in Germany as well as the fourth-l ...

. He studied music in his youth, specifically the bassoon, and has credited his

bassoon The bassoon is a musical instrument in the woodwind family, which plays in the tenor and bass ranges. It is composed of six pieces, and is usually made of wood. It is known for its distinctive tone color, wide range, versatility, and virtuosity ...

instructor, Herbert Tauscher, as his "most influential teacher". He was a graduate from the Hannover Waldorf School in 1975. Südhof studied medicine at the

RWTH Aachen University RWTH Aachen University (), in German ''Rheinisch-Westfälische Technische Hochschule Aachen'', is a German public research university located in Aachen, North Rhine-Westphalia, Germany. With more than 47,000 students enrolled in 144 study prog ...

Harvard University Harvard University is a Private university, private Ivy League research university in Cambridge, Massachusetts, United States. Founded in 1636 and named for its first benefactor, the History of the Puritans in North America, Puritan clergyma ...

, and then the

University of Göttingen The University of Göttingen, officially the Georg August University of Göttingen (, commonly referred to as Georgia Augusta), is a Public university, public research university in the city of Göttingen, Lower Saxony, Germany. Founded in 1734 ...

. In Göttingen Südhof worked on his doctoral thesis, in which he described the structure and function of

chromaffin cells Chromaffin cells, also called pheochromocytes (or phaeochromocytes), are neuroendocrine cells found mostly in the medulla of the adrenal glands in mammals. These cells serve a variety of functions such as serving as a response to stress, monito ...

, 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

Career and research

After a brief

postdoctoral fellowship A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary academ ...

in Whittaker's lab, Südhof moved to the United States in 1983, where he began postdoctoral training in the department of

molecular genetics Molecular genetics is a branch of biology that addresses how differences in the structures or expression of DNA molecules manifests as variation among organisms. Molecular genetics often applies an "investigative approach" to determine the st ...

at the University of Texas Health Science Center (now the

UT Southwestern Medical Center The University of Texas Southwestern Medical Center (UT Southwestern or UTSW) is a Public university, public Academic health science centre, academic health science center in Dallas, Texas. With approximately 23,000 employees, more than 3,000 ...

) in

Dallas Dallas () is a city in the U.S. state of Texas and the most populous city in the Dallas–Fort Worth metroplex, the List of Texas metropolitan areas, most populous metropolitan area in Texas and the Metropolitan statistical area, fourth-most ...

, Texas, under the supervision of Michael Stuart Brown and Joseph L. Goldstein. During his

postdoctoral research A postdoctoral fellow, postdoctoral researcher, or simply postdoc, is a person professionally conducting research after the completion of their doctoral studies (typically a PhD). Postdocs most commonly, but not always, have a temporary acade ...

fellow A fellow is a title and form of address for distinguished, learned, or skilled individuals in academia, medicine, research, and industry. The exact meaning of the term differs in each field. In learned society, learned or professional society, p ...

ship, Südhof worked to describe the role of the

LDL receptor The low-density lipoprotein receptor (LDL-R) is a mosaic protein of 839 amino acids (after removal of 21-amino acid signal peptide) that mediates the endocytosis of cholesterol-rich low-density lipoprotein (LDL). It is a cell-surface receptor ...

cholesterol Cholesterol is the principal sterol of all higher animals, distributed in body Tissue (biology), tissues, especially the brain and spinal cord, and in Animal fat, animal fats and oils. Cholesterol is biosynthesis, biosynthesized by all anima ...

metabolism, for which Brown and Goldstein were awarded the

in 1985. Südhof finished his postdoctoral training in 1986 and was elected to be an investigator of the

Howard Hughes Medical Institute The Howard Hughes Medical Institute (HHMI) is an American non-profit medical research organization headquartered in Chevy Chase, Maryland with additional facilities in Ashburn, Virginia. It was founded in 1953 by Howard Hughes, an American busin ...

. 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, Südhof moved to

and is currently the Avram Goldstein Professor in the School of Medicine as well as a Professor of Molecular & Cellular

Physiology Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

Psychiatry Psychiatry is the medical specialty devoted to the diagnosis, treatment, and prevention of deleterious mental disorder, mental conditions. These include matters related to cognition, perceptions, Mood (psychology), mood, emotion, and behavior. ...

, and

Neurology Neurology (from , "string, nerve" and the suffix wikt:-logia, -logia, "study of") is the branch of specialty (medicine) , medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous syst ...

. Südhof laid the foundations for his scientific career studying the synapse early while studying the mechanisms of

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

dependent hormone release from neuroendocrine cells for his doctoral thesis at the Max Planck Institute for Biophysical Chemistry. Südhof described the structure and function of

which are responsible for the release of

epinephrine Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands a ...

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic compound, organic chemical in the catecholamine family that functions in the brain and human body, body as a hormone, neurotransmitter and neuromodulator. The ...

and

endorphins Endorphins (contracted from endogenous morphine) are peptides produced in the brain that block the perception of pain and increase feelings of wellbeing. They are produced and stored in the pituitary gland of the brain. Endorphins are endogeno ...

from the medulla of the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

. Innervated by

sympathetic nervous system The sympathetic nervous system (SNS or SANS, sympathetic autonomic nervous system, to differentiate it from the somatic nervous system) is one of the three divisions of the autonomic nervous system, the others being the parasympathetic nervous sy ...

, chromaffin cells are important in the initiation of the

fight-or-flight response The fight-or-flight or the fight-flight-freeze-or-fawn (also called hyperarousal or the acute stress response) is a physiological reaction that occurs in response to a perceived harmful event, attack, or threat to survival. It was first describ ...

of animals when exposed to threatening stimuli. After completing his thesis in 1983, Südhof moved to

for his postdoctoral training where he began researching in the department of

under the supervision of Joseph L. Goldstein and Michael Stuart Brown. While a postdoctoral fellow, Südhof cloned the gene for the

low-density lipoprotein Low-density lipoprotein (LDL) is one of the five major groups of lipoprotein that transport all fat molecules around the body in extracellular water. These groups, from least dense to most dense, are chylomicrons (aka ULDL by the overall density ...

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 Familial hypercholesterolemia (FH) is a genetic disorder characterized by high cholesterol levels, specifically very high levels of low-density lipoprotein cholesterol (LDL cholesterol), in the blood and early cardiovascular diseases. The mos ...

. As a result of the discovery, LDL receptor function had also elucidated the principle of

receptor-mediated endocytosis Receptor-mediated endocytosis (RME), also called clathrin-mediated endocytosis, is a process by which cells absorb metabolites, hormones, proteins – and in some cases viruses – by the inward budding of the plasma membrane (invagination). This ...

—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, Südhof started his own laboratory at UT Southwestern in 1986. Briefly continuing work with Goldstein and Brown, Südhof helped identify a DNA element in the LDL gene that produced

sterol A sterol is any organic compound with a Skeletal formula, skeleton closely related to Cholestanol, cholestan-3-ol. The simplest sterol is gonan-3-ol, which has a formula of , and is derived from that of gonane by replacement of a hydrogen atom on ...

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

and steroid hormones. Discovery of sterol regulatory elements and LDL receptor function led to the subsequent development of

statin Statins (or HMG-CoA reductase inhibitors) are a class of medications that lower cholesterol. They are prescribed typically to people who are at high risk of cardiovascular disease. Low-density lipoprotein (LDL) carriers of cholesterol play ...

derived cholesterol medications such as

atorvastatin Atorvastatin, sold under the brand name Lipitor among others, is a statin medication used to prevent cardiovascular disease in those at high risk and to treat abnormal lipid levels. For the prevention of cardiovascular disease, statins are a ...

(Lipitor)—the top-selling branded pharmaceutical drug in the world in 2008. Südhof 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 Südhof began his work, majority of neuroscience research was aimed at the postsynaptic neuron and its role in learning and memory. Indeed, Thomas Südhof is credited with discovering much of the machinery mediating neurotransmitter release and presynaptic plasticity in his 21 years at UT Southwestern. Südhof 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 SNARE proteins – "Soluble NSF attachment protein, SNAP REceptors" – are a large protein family consisting of at least 24 members in yeasts and more than 60 members in mammalian and plant cells. The primary role of SNARE proteins is to m ...

complex. Südhof 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, Südhof'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 Syntaxins are a family of membrane integrated Q-SNARE proteins participating in exocytosis. Domains Syntaxins possess a single C-terminal transmembrane domain, a SNARE domain (known as H3), and an N-terminal regulatory domain (Habc). Syntaxi ...

, 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. Südhof 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 Südhof is on synapse formation and specifications. Südhof 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, Südhof identified mutations in these proteins as a factor in inherited

autism Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...

. Südhof 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. Südhof 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, Südhof 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. Südhof'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

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. Südhof 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". Three more papers were retracted in 2024.

Science and policy

Südhof recently also engages in scientific ethics as exemplified by his recent work at

PLOS Biology ''PLOS Biology'' is a monthly peer-reviewed scientific journal covering all aspects of biology. Publication began on October 13, 2003. It is the first journal published by the Public Library of Science. The editor-in-chief is Nonia Pariente. In ...

''Truth in Science Publishing: A personal Perspective'' and various interviews including his discussion about music, policy and medicine with ''The Lancet''. In 2017, he published an article in ''

The Washington Post ''The Washington Post'', locally known as ''The'' ''Post'' and, informally, ''WaPo'' or ''WP'', is an American daily newspaper published in Washington, D.C., the national capital. It is the most widely circulated newspaper in the Washington m ...

'' on basic research vs. drug development.

Other activities

In 2023, Südhof was appointed by United Nations Secretary General

António Guterres António Manuel de Oliveira Guterres (born 30 April 1949) is a Portuguese politician and diplomat who is serving as the ninth and current secretary-general of the United Nations since 2017. A member of the Socialist Party (Portugal), ...

to the United Nations' Scientific Advisory Board. Corporate board memberships have included: * Neurocentria, member of the scientific advisory board (since 2023) *

Sanofi Sanofi S.A. is a French Multinational corporation, multinational pharmaceutical and healthcare company headquartered in Paris, France. The corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 200 ...

, independent member of the board of directors (2016–2024)

Awards and honors

* 1993 W. Alden Spencer Award from

Columbia University Columbia University in the City of New York, commonly referred to as Columbia University, is a Private university, private Ivy League research university in New York City. Established in 1754 as King's College on the grounds of Trinity Churc ...

(shared with

Richard Scheller Richard H. Scheller (born 30 October 1953) is the former chief science officer and head of therapeutics at 23andMe and the former executive vice president of research and early development at Genentech. He was a professor at Stanford University f ...

) * 1994 Wilhelm Feldberg Award * 1997 Roger Eckert Award Lecture, Göttingen * 1997 U.S. National Academy Award in Molecular Biology (shared with

) * 2002 Elected to the

National Academy of Sciences The National Academy of Sciences (NAS) is a United States nonprofit, NGO, non-governmental organization. NAS is part of the National Academies of Sciences, Engineering, and Medicine, along with the National Academy of Engineering (NAE) and the ...

of the U.S.A. * 2003 Metlife Foundation Award for Medical Research in Alzheimer's Disease (shared with Roberto Malinow) * 2004 Bristol-Myers Squibb Award for Distinguished Achievement in Neuroscience Research * 2004 Ulf von Euler Award Lecture,

Karolinska Institute The Karolinska Institute (KI; ; sometimes known as the (Royal) Caroline Institute in English) is a research-led medical university in Solna within the Stockholm urban area of Sweden and one of the foremost medical research institutes globally ...

* 2007 Elected to the

Institute of Medicine The National Academy of Medicine (NAM), known as the Institute of Medicine (IoM) until 2015, is an American nonprofit, non-governmental organization. The National Academy of Medicine is a part of the National Academies of Sciences, Engineerin ...

* 2008 Bernhard Katz Award, Biophysical Society (shared with Reinhard Jahn) * 2008 Passano Foundation Award * 2010

Kavli Prize The Kavli Prize was established in 2005 as a joint venture of the Norwegian Academy of Science and Letters, the Norwegian Ministry of Education and Research, and the Kavli Foundation (United States), Kavli Foundation. It honors, supports, and r ...

(shared with

and James Rothman) * 2013

Albert Lasker Award for Basic Medical Research The Albert Lasker Award for Basic Medical Research is one of the Lasker Award, prizes awarded by the Lasker Foundation for a fundamental discovery that opens up a new area of biomedical science. The award frequently precedes a Nobel Prize in Phys ...

(shared with

) * 2013

- shared with Randy Schekman and James Rothman * 2014 Golden Plate Award of the

American Academy of Achievement The American Academy of Achievement, colloquially known as the Academy of Achievement, is a nonprofit educational organization that recognizes some of the highest-achieving people in diverse fields and gives them the opportunity to meet one ano ...

* 2017 Elected a Foreign Member of the Royal Society (ForMemRS) * 2023 Awarded Joseph Carrier C.S.C. Science Medal from the University of Notre Dame.

Personal life

Südhof is married to Lu Chen, a professor of neurosurgery and of psychiatry and behavioral sciences at Stanford University. The couple have three children. Südhof has four more children from his previous marriage with Annette Südhof.

References

External links

* {{DEFAULTSORT:Sudhof, Thomas Christian 1955 births Living people Scientists from Göttingen American biochemists Howard Hughes Medical Investigators American Nobel laureates Nobel laureates in Physiology or Medicine Stanford University School of Medicine faculty Members of the United States National Academy of Sciences Foreign members of the Royal Society University of Göttingen alumni University of Texas Southwestern Medical Center alumni Waldorf school alumni German biochemists German Nobel laureates Emigrants from West Germany to the United States Recipients of the Albert Lasker Award for Basic Medical Research Knights Commander of the Order of Merit of the Federal Republic of Germany Kavli Prize laureates in Neuroscience Members of the German National Academy of Sciences Leopoldina RWTH Aachen University alumni Members of the National Academy of Medicine