NINDS Mourns the Passing of Reese
Dr. Thomas (Tom) Reese, a senior investigator and chief of the section on structural cell biology of the National Institute of Neurological Disorders and Stroke (NINDS) Intramural Research Program, died on October 11 at the age of 89. His scientific work spanned six decades.
Reese was a world leader in structural neuroscience, developing cutting-edge applications that fundamentally changed the understanding of synapses and cells in the brain, as well as the barrier separating the brain from the bloodstream. His many contributions to neuroscience and cell biology led to his election to the National Academy of Sciences in 1987.
Reese earned his undergraduate degree from Harvard College and his medical degree from Columbia College of Physicians and Surgeons. He then served as a research medical officer at NINCDS (now NINDS) and within four years became head of his laboratory.
In the late 1960s, Reese used electron microscopy (EM) to examine the structural basis of the blood-brain barrier. His experiments with Dr. Morris Karnovsky showed that proteins in the bloodstream are prevented from entering the brain by tight junctions between vascular endothelial cells. This discovery continues to influence the design and delivery of therapeutics for brain diseases.
In the 1970s, Reese and his postdoc Dr. John Heuser carefully examined electron micrographs to delineate the different steps by which the synaptic vesicle membrane is recycled for subsequent reuse at the neuromuscular junction. They went on to develop a revolutionary technique to precisely time rapid tissue freezing with electrical stimulation of motor neurons to capture the fleeting moment when neurotransmitter release occurs. This “freeze-slamming” technique conclusively demonstrated, for the first time, that neurotransmitters are released by fusion of synaptic vesicles with the presynaptic plasma membrane.
While maintaining his appointment at NIH, Reese also set up a lab at the Marine Biological Laboratory (MBL) in Woods Hole, Mass., to study giant axons in squid. He used his rapid-freeze EM methods in conjunction with video microscopy to observe fast axonal transport in real time and then visualize the axons transporting cargo. These techniques enabled Reese and his collaborators to discover kinesins—a class of motor proteins that are critical for axonal transport, mitosis and other cellular functions. Reese maintained his work at Woods Hole full time for most of the 1980s and was active in the MBL community and its educational programs for more than 40 years.
In the 2000s, Reese focused on the structural organization of the postsynaptic density (PSD), a specialized, extensive protein complex associated with the postsynaptic membrane. He discovered that PSD is a dynamic structure that changes shape and protein composition rapidly with synaptic activity. He also discovered that a new subcellular compartment, which he termed the pallium, is a principal site for regulatory machinery that underlies transmitter receptor targeting to and from synaptic microdomains. PSD is now recognized to contain intricate molecular machinery critical to neurotransmitter signaling.
Toward the end of his career, Reese focused on how the nervous system evolves. He worked with his colleague and wife, Dr. Carolyn Smith, on Trichoplax—a tiny disk-shaped marine animal that has no synapses but can perform simple behaviors such as movement and digestion. They used Reese’s tried-and-true freezing and microscopy techniques to identify cells that could control locomotion and feeding to gain insights into how animals without synapses can generate behavior. Reese’s philosophy to “learn by looking” drove him to develop cutting-edge techniques that were used to achieve fundamental insights into how synapses and cells work.
“Tom will be missed dearly, but his legacy will live on through his family, his seminal contributions to structural neurobiology, and generations of scientists who trained under, worked with, and were inspired by him,” said NINDS Scientific Director Dr. Jeffrey DIamond, who penned the above obituary.