Thomas Christian Südhof (German pronunciation: [ˈtoːmas ˈzyːtˌhoːf]; born December 22, 1955), ForMemRS, is a German-American biochemist who studies how brain cells communicate. He is now a professor in the school of medicine, in the department of molecular and cellular physiology, and also holds positions by courtesy in neurology, psychiatry, and behavioral sciences at Stanford University.

Südhof, along with James Rothman and Randy Schekman, received the 2013 Nobel Prize in Physiology or Medicine for their research on vesicle trafficking.

Early life and education

Südhof was born in Göttingen, Germany, in 1955. He grew up in Göttingen and Hannover. When he was young, he studied music, especially the bassoon. He said his bassoon teacher, Herbert Tauscher, was his most important teacher. He finished school at the Hannover Waldorf School in 1975. Südhof studied medicine at RWTH Aachen University, Harvard University, and the University of Göttingen. In Göttingen, he worked on his doctoral research, which focused on the structure and function of chromaffin cells. This research took place at the Max Planck Institute for Biophysical Chemistry in the lab of Victor P. Whittaker. In 1982, he received his medical doctor degree (Dr.med.) from the University of Göttingen.

Career and research

After completing a short postdoctoral training in Whittaker's lab, Südhof moved to the United States in 1983. He began postdoctoral training in the department of molecular genetics at the University of Texas Health Science Center (now UT Southwestern Medical Center) in Dallas, Texas, under the guidance of Michael Stuart Brown and Joseph L. Goldstein.

During his postdoctoral research, Südhof studied the role of the LDL receptor in cholesterol metabolism. Brown and Goldstein were awarded the Nobel Prize in Physiology or Medicine in 1985 for their work on this topic. Südhof completed his postdoctoral training in 1986 and became an investigator at the Howard Hughes Medical Institute. He then started his own laboratory at UT Southwestern Medical Center, where he focused on molecular and cellular neuroscience related to synapses for over 20 years.

In 2008, Südhof moved to Stanford University. He is currently the Avram Goldstein Professor in the School of Medicine and also teaches in the departments of Molecular & Cellular Physiology, Psychiatry, and Neurology.

Südhof began his scientific career by studying synapses during his doctoral research at the Max Planck Institute for Biophysical Chemistry. He studied how neurotransmitters are released from neuroendocrine cells. He described the structure and function of chromaffin cells, which release epinephrine, norepinephrine, and endorphins from the adrenal gland. These cells are controlled by the sympathetic nervous system and help animals respond to danger through the fight-or-flight reaction.

After finishing his doctorate in 1983, Südhof joined UT Southwestern Medical Center for postdoctoral training. He worked in the molecular genetics department under the supervision of Goldstein and Brown. As a postdoctoral fellow, Südhof cloned the gene for the low-density lipoprotein (LDL) receptor and explained how cholesterol regulates its activity. LDL receptors in the liver bind to cholesterol in the blood, removing it from circulation. This process is critical for controlling blood cholesterol levels. Problems with this process are linked to a condition called familial hypercholesterolemia. Goldstein and Brown were awarded the Nobel Prize in 1985 for their discovery.

After completing his postdoctoral training, Südhof started his own laboratory at UT Southwestern in 1986. He continued working with Goldstein and Brown, helping identify a DNA segment in the LDL gene that controls cholesterol production. This segment, called a sterol regulatory sequence, plays a key role in making sterols, which are essential for life. Important sterols in humans include cholesterol and steroid hormones. Discoveries related to sterol regulation and LDL receptors led to the development of cholesterol-lowering drugs like atorvastatin (Lipitor), one of the most sold medications worldwide in 2008.

Südhof began his independent research in neuroscience in 1986, focusing on synaptic transmission from the presynaptic nerve terminal. Before his work, most neuroscience research focused on the postsynaptic neuron and its role in learning and memory. Südhof discovered many proteins involved in neurotransmitter release, such as synaptotagmin, which senses calcium and triggers the release of neurotransmitters. He also identified proteins like RIMs and Muncs (such as Munc13 and Munc18), which help fuse neurotransmitter vesicles with nerve cell membranes. His research also uncovered the roles of SNARE complex proteins, including synaptobrevin, syntaxin, and SNAP25, in vesicle fusion. Südhof also explained how tetanus and botulinum toxins block neurotransmitter release by cutting synaptobrevin and SNAP25, respectively.

Südhof also made important contributions to understanding how synapses form. He discovered molecules like neurexins (on presynaptic neurons) and neuroligins (on postsynaptic neurons), which connect across synapses to create physical bridges. The variety of these molecules allows for specific connections between neurons. He also studied other proteins, such as SynCAM and Latrophilins, involved in synapse formation. Südhof found that mutations in these proteins are linked to inherited autism. He continues to study how these molecules find each other to form synapses, their regulation, and how their diversity is controlled.

At Stanford University, Südhof continues research on synapse formation, maintenance, and neurotransmitter release. With Marius Wernig, he developed a method to create human neurons from patient cells or genetically modified cells linked to neuropsychiatric or neurodevelopmental disorders. His work has advanced understanding of diseases like Alzheimer’s, schizophrenia, and autism. He collaborates with researchers at the Howard Hughes Medical Institute to create mouse models for mutated synaptic genes, aiming to improve understanding of neurological disorders. He also participates in the Cure Alzheimer’s Fund Research Consortium.

Südhof’s research has been reviewed on PubPeer, where some critics raised concerns about over 30 of his papers. These concerns included possible image manipulation, repeated data, mislabeled figures, and questions about the statistical significance of results. Südhof claims most criticisms are unfounded or relate to minor errors that do not affect scientific conclusions. He states that raw data is publicly available for review.

Other activities

In 2023, Südhof was named to the United Nations' Scientific Advisory Board by United Nations Secretary General António Guterres.

Personal life

Thomas Südhof is married to Lu Chen, who is a professor in neurosurgery and psychiatry and behavioral sciences at Stanford University. The couple has three children together. Thomas Südhof also has four additional children from his earlier marriage to Annette Südhof.