Michael D. Gershon, MD

Michael Gershon MD: “Serotonin is a sword and a shield of the bowel: serotonin plays offense and defense.“ Photo credit: Columbia University Medical School, MD/PhD Program

 

Michael D. Gershon, is Professor of Pathology and Cell Biology, at Columbia University Medical School and Center. Gershon has been called the “father of neurogastroenterology“ because, in addition to his seminal work on neuronal control of gastrointestinal (GI) behavior and development of the enteric nervous system (ENS), his classic trade book, The Second Brain, has made physicians, scientists, and the lay public aware of the significance of the unique ability of the ENS to regulate GI activity in the absence of input from the brain and spinal cord. Gershon’s demonstration that serotonin is an enteric neurotransmitter was the first indication that the ENS is more than a collection of cholinergic relay neurons transmitting signals from the brain to the bowel. He was the first to identify intrinsic primary afferent neurons that initiate peristaltic and secretory reflexes and he demonstrated that these cells are activated by the mucosal release of serotonin. Dr. Gershon has published almost 400 peer-reviewed papers including major contributions relative to disorders of GI motility, including irritable bowel syndrome, identification of serotonin as a GI neurotransmitter and the initial observation in the gut of intrinsic sensory nerve cells that trigger propulsive motor activity. Dr. Gershon also discovered that the serotonin transporter (SERT) is expressed by enterocytes (cells that line the lumen of the gut) as well as by enteric neurons and is critical in the termination of serotonin-mediated effects.

 

Dr. Gershon has identified roles in GI physiology that specific subtypes of serotonin receptor play and he has provided evidence that serotonin is not only a neurotransmitter and a paracrine factor that initiates motile and secretory reflexes, but also as a hormone that affects bone resorption and inflammation. He has called serotonin “a sword and shield of the bowel“ because it is simultaneously proinflammatory and neuroprotective. Mucosal serotonin triggers inflammatory responses that oppose microbial invasion, while neuronal serotonin protects the ENS from the damage that inflammation would otherwise cause. Neuron-derived serotonin also mobilizes precursor cells, which are present in the adult gut, to initiate the genesis of new neurons, an adult function that reflects a similar essential activity of early-born serotonergic neurons in late fetal and early neonatal life to promote development of late-born sets of enteric neurons.

 

Dr. Gershon has made many additional contributions to ENS development, including the identification of necessary guidance molecules, adhesion proteins, growth and transcription factors; his observations suggest that defects that occur late in ENS development lead to subtle changes in GI physiology that may contribute to the pathogenesis of functional bowel disorders. More recently, Drs. Michael and Anne Gershon have demonstrated that varicella zoster virus (VZV) infects, becomes latent, and reactivates in enteric neurons, including those of humans. They have demonstrated that “enteric zoster (shingles)“ occurs and may thus be an unexpected cause of a variety of gastrointestinal disorders, the pathogenesis of which is currently unknown.

 

Born in New York City in 1938, Dr. Michael D. Gershon received his B.A. degree in 1958 “with distinction from Cornell University and his M.D. in 1963, again from Cornell. Gershon received postdoctoral training with Edith Bulbring in Pharmacology at Oxford University before returning to Cornell as an Assistant Professor of Anatomy in 1967. He was promoted to Professor before leaving Cornell to Chair the Department of Anatomy & Cell Biology at Columbia University’s College of P&S from 1975-2005. Gershon is now a Professor of Pathology & Cell Biology at Columbia.

 

Gershon’s contributions to the identification, location, and functional characterization of enteric serotonin receptors have been important in the design of drugs to treat irritable bowel syndrome, chronic constipation, and chemotherapy-associated nausea. Gershon’s discovery that the serotonin transporter (SERT), which terminates serotonergic signaling, is expressed in the bowel both by enterocytes and neurons opened new paths for research into the pathophysiology of irritable bowel syndrome and inflammatory bowel disease. He has linked mucosal serotonin to inflammation and neuronal serotonin to neuroprotection and the generation of new neurons from adult stem cells. These discoveries have led to the new idea that the function of serotonin is not limited to paracrine signaling and neurotransmission in the service of motility and secretion, but is also a sword and a shield of the gut.

 

Gershon has teamed with his wife, Anne Gershon, to show that the mannose 6-phosphate receptor plays critical roles in the entry and exit of varicella zoster virus (VZV). The Gershons have also developed the first animal model of VZV disease, which enables lytic and latent infection as well as reactivation to be studied in isolated enteric neurons. The Gershons have also shown that following varicella, VZV establishes latency in the human ENS. Finally, Gershon has made major contributions to understanding the roles played by a number of critical transcription and growth factors in enabling emigres from the neural crest to colonize the bowel, undergo regulated proliferation, find their appropriate destinations in the gut wall, and terminally differentiate into the most phenotypcially diverse component of the peripheral nervous system.

 

Dr. Michael Gershon has devoted his career to understanding the human bowel (the stomach, esophagus, small intestine, and colon). His thirty years of research have led to an extraordinary rediscovery: nerve cells in the gut that act as a brain. This “second brain“ can control our gut all by itself. Our two brains — the one in our head and the one in our bowel — must cooperate. If they do not, then there is chaos in the gut and misery in the head — everything from “butterflies“ to cramps, from diarrhea to constipation.

 

Gershon’s groundbreaking book, The Second Brain represents a quantum leap in medical knowledge and is already benefiting patients whose symptoms were previously dismissed as neurotic or “it’s all in your head.“ Dr. Gershon’s research, clearly demonstrates that the human gut actually has a brain of its own. This remarkable scientific breakthrough offers fascinating proof that “gut instinct“ is biological, a function of the second brain. An alarming number of people suffer from heartburn, nausea, abdominal pain, cramps, diarrhea, constipation, or related problems. Often thought to be caused by a “weakness“ of the mind, these conditions may actually be a reflection of a disorder in the second brain. The second brain, located in the bowel, normally works smoothly with the brain in the head, enabling the head-brain to concentrate on the finer pursuits of life while the gut-brain attends to the messy business of digestion. A breakdown in communication between the two brains can lead to stomach and intestinal trouble, causing sufferers great abdominal grief and too often labeling them as neurotic complainers. Dr. Gershon’s research into the second brain provides understanding for those who suffer from gut-related ailments and offers new insight into the origin, extent, and management. The culmination of his work is an extraordinary contribution to the understanding of gastrointestinal illnesses, as well as a fascinating glimpse into how our gut really works.

 

A light touch: The irreplaceable, indomitable, Stephen Colbert interviews the great Michael Gershon MD about the Second Brain, in the gut

 

Michael Gershon clearly explains some of his research. This is video one out of seven. You can find the other six

videos on YouTube.

 

Very short student note regarding Dr Gershon

 

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