Thomas C. Südhof

Thomas Christian Südhof (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.

A German native, Südhof was born in Göttingen in 1955.

He spent his childhood in Göttingen and Hannover.

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, and then the University of Göttingen.

In Göttingen Südhof 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 Göttingen.

After a brief postdoctoral fellowship in Whittaker's lab, Südhof 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.

After completing his thesis in 1983, Südhof 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, Südhof 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.

During his postdoctoral research fellowship, Südhof 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.

Goldstein and Brown were awarded the Nobel Prize in Physiology or Medicine for the discovery 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.

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 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.

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 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, 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.

In 2008, Südhof 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.

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 Max Planck Institute for Biophysical Chemistry.

Südhof 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.

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.

Südhof, James Rothman and Randy Schekman are the 2013 Nobel Prize in Physiology or Medicine laureates for their work on vesicle trafficking.

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".https://www.thetransmitter.org/retraction/nobel-prize-winner-thomas-sudhof-retracts-study/