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

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

, 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. Südhof,

James Rothman James Edward Rothman (born November 3, 1950) is an American biochemist. He is the Fergus F. Wallace Professor of Biomedical Sciences at Yale University, the Chairman of the Department of Cell Biology at Yale School of Medicine, and the Director ...

and

Randy Schekman Randy Wayne Schekman (born December 30, 1948) is an American cell biologist at the University of California, Berkeley, former editor-in-chief of ''Proceedings of the National Academy of Sciences'' and former editor of ''Annual Review of Cell and ...

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, accord ...

laureates for their work on

vesicle Vesicle may refer to: ; In cellular biology or chemistry * Vesicle (biology and chemistry) In cell biology, a vesicle is a structure within or outside a cell, consisting of liquid or cytoplasm enclosed by a lipid bilayer. Vesicles form nat ...

trafficking.

Early life and education

A German native, Südhof was born in

Göttingen Göttingen (, , ; nds, Chöttingen) is a university city in Lower Saxony, central Germany, the capital of the eponymous district. The River Leine runs through it. At the end of 2019, the population was 118,911. General information The ori ...

in 1955. He spent his childhood in Göttingen and

Hannover Hanover (; german: Hannover ; nds, Hannober) is the capital and largest city of the German state of Lower Saxony. Its 535,932 (2021) inhabitants make it the 13th-largest city in Germany as well as the fourth-largest city in Northern Germany ...

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

Harvard University Harvard University is a private Ivy League research university in Cambridge, Massachusetts. Founded in 1636 as Harvard College and named for its first benefactor, the Puritan clergyman John Harvard, it is the oldest institution of high ...

, and then the

University of Göttingen The University of Göttingen, officially the Georg August University of Göttingen, (german: Georg-August-Universität Göttingen, known informally as Georgia Augusta) is a public research university in the city of Göttingen, Germany. Founded ...

. 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, monitor ...

, at the

Max Planck Institute for Biophysical Chemistry The Max Planck Institute for Biophysical Chemistry (german: Max-Planck-Institut für biophysikalische Chemie), also known as the Karl-Friedrich Bonhoeffer Institute (german: Karl-Friedrich-Bonhoeffer-Institut), was a research institute of the Ma ...

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). The ultimate goal of a postdoctoral research position is to pu ...

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 sub-field 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 ...

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 academic health science center in Dallas, Texas. With approximately 18,800 employees, more than 2,900 full-time faculty, and nearly 4 million outpatient ...

) in

Dallas Dallas () is the List of municipalities in Texas, third largest city in Texas and the largest city in the Dallas–Fort Worth metroplex, the List of metropolitan statistical areas, fourth-largest metropolitan area in the United States at 7.5 ...

, Texas, under the supervision of

Michael Stuart Brown Michael Stuart Brown ForMemRS NAS AAA&S APS (born April 13, 1941) is an American geneticist and Nobel laureate. He was awarded the Nobel Prize in Physiology or Medicine with Joseph L. Goldstein in 1985 for describing the regulation of choles ...

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). The ultimate goal of a postdoctoral research position is to pu ...

fellow A fellow is a concept whose exact meaning depends on context. In learned or professional societies, it refers to a privileged member who is specially elected in recognition of their work and achievements. Within the context of higher education ...

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 any of a class of certain organic molecules called lipids. It is a sterol (or modified steroid), a type of lipid. Cholesterol is biosynthesized by all animal cells and is an essential structural component of animal cell mem ...

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. 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 Stanford University and is currently the Avram Goldstein Professor in the

School of Medicine A medical school is a tertiary educational institution, or part of such an institution, that teaches medicine, and awards a professional degree for physicians. Such medical degrees include the Bachelor of Medicine, Bachelor of Surgery (MBBS, M ...

as well as a Professor of Molecular & Cellular

Physiology Physiology (; ) is the scientific study of functions and mechanisms in a living system. As a sub-discipline of biology, physiology focuses on how organisms, organ systems, individual organs, cells, and biomolecules carry out the chemical ...

Psychiatry Psychiatry is the specialty (medicine), medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psych ...

, and

Neurology Neurology (from el, νεῦρον (neûron), "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the brain, the spinal ...

. Thomas C. Südhof 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

. Südhof described the structure and function of

which are responsible for the release of epinephrine,

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad' ...

and endorphins from the

medulla Medulla or Medullary may refer to: Science * Medulla oblongata, a part of the brain stem * Renal medulla, a part of the kidney * Adrenal medulla, a part of the adrenal gland * Medulla of ovary, a stroma in the center of the ovary * Medulla of t ...

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 cortex whic ...

. Innervated by sympathetic nervous system, chromaffin cells are important in the initiation of the

fight-or-flight response The fight-or-flight or the fight-flight-or-freeze response (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 des ...

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

. 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 dens ...

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, Thomas 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 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 A steroid hormone is a steroid that acts as a hormone. Steroid hormones can be grouped into two classes: corticosteroids (typically made in the adrenal cortex, hence ''cortico-'') and sex steroids (typically made in the gonads or placenta). Withi ...

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

statin Statins, also known as HMG-CoA reductase inhibitors, are a class of lipid-lowering medications that reduce illness and mortality in those who are at high risk of cardiovascular disease. They are the most common cholesterol-lowering drugs. Low ...

derived cholesterol medications such as

atorvastatin Atorvastatin 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 first-line treatment. It is taken by mouth. Common ...

(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 – " SNAP REceptor" – are a large protein family consisting of at least 24 members in yeasts, more than 60 members in mammalian cells, and some numbers in plants. The primary role of SNARE proteins is to mediate vesicle f ...

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 Synaptobrevins (''synaptobrevin isotypes 1-2'') are small integral membrane proteins of secretory vesicles with molecular weight of 18 kilodalton (kDa) that are part of the vesicle-associated membrane protein (VAMP) family. Synaptobrev ...

, 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). Syntaxin ...

, in the cell membrane, and

SNAP25 Synaptosomal-Associated Protein, 25kDa (SNAP-25) is a Target Soluble NSF (''N''-ethylmaleimide-sensitive factor) Attachment Protein Receptor ( t-SNARE) protein encoded by the ''SNAP25'' gene found on chromosome 20p12.2 in humans. SNAP-25 is a com ...

, 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 Thomas Südhof is on synapse formation and specifications. Südhof discovered a number of key molecules in this process such as

neurexins Neurexins (NRXN) are a family of presynaptic cell adhesion proteins that have roles in connecting neurons at the synapse. They are located mostly on the presynaptic membrane and contain a single transmembrane domain. The extracellular domain ...

, present on presynaptic neurons, and

neuroligins Neuroligin (NLGN), a type I membrane protein, is a cell adhesion protein on the postsynaptic membrane that mediates the formation and maintenance of synapses between neurons. Neuroligins act as ligands for β-neurexins, which are cell ...

, 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. 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. Thomas Südhof currently continues his work on synapse formation, maintenance as well as synaptic releases in his laboratory at Stanford University. Additionally, together with Dr. 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 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 Cure Alzheimer's Fund (CAF) is an American non-profit organizationGuideStar Accessed 26 March 2014.Better Business Bureau. Accessed 26 March 2014. based in Wellesley, Massachusetts. It supports and funds research focusing on understanding and poten ...

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 a ...

''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'' (also known as the ''Post'' and, informally, ''WaPo'') is an American daily newspaper published in Washington, D.C. It is the most widely circulated newspaper within the Washington metropolitan area and has a large nati ...

'' on basic research vs. drug development.

Other activities

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

, Independent Member of the Board of Directors (since 2016)

Awards and honors

* 1993 W. Alden Spencer Award from

Columbia University Columbia University (also known as Columbia, and officially as Columbia University in the City of New York) is a private research university in New York City. Established in 1754 as King's College on the grounds of Trinity Church in Manhatt ...

(shared with Richard Scheller) * 1994 Wilhelm Feldberg Award * 1997 Roger Eckert Award Lecture, Göttingen * 1997 U.S. National Academy Award in Molecular Biology (shared with Richard Scheller) * 2002 Elected to the National Academy of Sciences of the U.S.A. * 2003 Metlife Foundation Award for Medical Research in Alzheimer's Disease (shared with

Roberto Malinow Roberto Malinow. M.D., Ph.D. is an Argentinian-born American neuroscientist at the University of California, San Diego. He is currently a distinguished professor of neurobiology and neurosciences, and holds the Shiley Chair in Alzheimer's Disease ...

) * 2004

Bristol-Myers Squibb Award Between 1977 and 2006, the Bristol-Myers Squibb Foundation presented annual awards of US$50,000 to scientists for distinguished achievements in fields such as cancer, infectious disease, neuroscience, nutrition, and cardiovascular disease. The rec ...

for Distinguished Achievement in Neuroscience Research * 2004

Ulf von Euler Ulf Svante von Euler (7 February 1905 – 9 March 1983) was a Swedish physiologist and pharmacologist. He shared the Nobel Prize in Physiology or Medicine in 1970 for his work on neurotransmitters. Life Ulf Svante von Euler-Chelpin was born in ...

Award Lecture,

Karolinska Institute The Karolinska Institute (KI; sv, Karolinska Institutet; sometimes known as the (Royal) Caroline Institute in English) is a research-led Medical school, medical university in Solna Municipality, Solna within the Stockholm urban area of Sweden. ...

* 2007 Elected to the Institute of Medicine * 2008 Bernhard Katz Award, Biophysical Society (shared with

Reinhard Jahn Reinhard Jahn (born 21 December 1950) is a German biophysicist and neurobiologist known for his studies of cellular membrane fusion. For these investigations, he has been honored with numerous awards, including the 2000 Leibniz Award. Jahn is c ...

) * 2008

Passano Foundation The Passano Foundation, established in 1945, provides an annual award to a research scientist whose work – done in the United States – is thought to have immediate practical benefits. Many Passano laureates have subsequently won the Nobel Priz ...

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. It honors, supports, and recognizes scientists for outstan ...

(shared with Richard Scheller and

) * 2013 Albert Lasker Award for Basic Medical Research (shared with Richard Scheller) * 2013

- shared with

and

* 2014 Golden Plate Award of the

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

* 2017 Elected a Foreign Member of the Royal Society (ForMemRS)

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 German emigrants 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 Academy of Sciences Leopoldina RWTH Aachen University alumni