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July 10, 2017What's New
Target Health has been a member of the Clinical Trials Transformation Initiative (CTTI) since 2008, and we strongly support CTTI's mission of transforming and modernizing clinical trials. While it has been a long journey, there have been many fruits of our labors, including the Registry Work Stream, which culminated in a CTTI Webinar in May, and now an NIH Collaboratory Webinar being held this month.
Here are the Collaboratory details:
On Friday, July 21, 2017, 1:00-2:00 p.m. EDT, John Laschinger, MD, Medical Officer, Center for Devices and Radiological Health, Clinical Trials Operations and Biostatistics Branch, US FDA, and Jules Mitchel, MBA, PhD, President, Target Health Inc. will be presenting the CTTI Registry Trials Project: Evaluation and Design of Registries for Conducting Clinical Trials. For more information go to https://www.nihcollaboratory.org/Lists/Calendar/DispForm.aspx?ID=253.
This webinar covers CTTI's recommendations on conducting clinical trials using registries. Those interested in evaluating or designing a registry for the purposes of conducting clinical trials can learn more about the project's tools, intended for the following purposes:
1. To determine if an existing registry is appropriate for embedding clinical trials
2. To assess if an existing registry contains the elements needed to support a clinical trial
3. To design a new registry suitable for embedding clinical trials
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors. Please visit the Target Health Website, and if you like the weekly newsletter, ON TARGET, you'll love the Blog.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
July 10, 2017Quiz
The word dermatology derives from the 1) ___ dermatos and derma, meaning skin. Originally it meant to flay skin.
Chondrodermatitis nodularis chronica helicis (CNH), also known as chondrodermatitis nodularis helicis, is a small, nodular, tender, chronic inflammatory lesion occurring on the helix of the 2) ___. CNH is a common, benign, painful condition of the helix or antihelix of the ear which more often affects middle-aged or older men, but cases are also reported in women. In a 2006 report by Rex et al., of 74 patients treated for CNH, 72.9% of patients were 3) ___ while 16.2% were women.
Pediatric cases of CNH have also been reported, with one case reported in a 9-month-old infant. This case indicated that the infant slept on the ear of occurrence, where she developed 2 nodules. The infant had also recently started sleeping on a hard pillow, which may have contributed to the lesion. An excisional biopsy of the lesion at 9 months showed histologic features consistent with CNH. The papule resolved with a change in sleeping 4) ___ over 6 months.
The exact cause of CNH is unknown, although most experts believe it is caused by prolonged and excessive pressure. Several anatomic features of the ear predispose persons to the development of this condition. The ear has relatively little subcutaneous tissue for insulation and padding, and only small dermal blood 5) ___ supply the epidermis, dermis, perichondrium, and cartilage. Dermal inflammation, edema, and necrosis from trauma, cold, actinic damage, or pressure probably initiate the disease. In most cases, focal pressure on the stiff cartilage most likely produces damage to the cartilage and overlying skin. Anatomic features of the ear, as listed above, prevent adequate healing and lead to secondary perichondritis. The 6) ___ ear is more commonly involved. A 2009 report concluded that specific perichondrial arteriolar changes may be the cause of CNH. Although physicians have regarded CNH as an idiopathic disorder with no systemic associations, exceptions to this have been noted. CNH may also occasionally be associated with autoimmune or connective-tissue disorders, including autoimmune thyroiditis, lupus erythematosus, dermatomyositis, and scleroderma. Such cases may be more common in pediatric or young adult female patients. A 2009 report detailed CNH in monozygotic twins, suggesting a possible 7) ___ factor. The exact incidence of CNH is unknown. While the incidence in patients age 60-80 years is predominantly male, cases presenting in young 8) ___ appear to be associated with evidence of underlying systemic illness in some instances. CNH has been reported to occur most commonly in fair-skinned individuals with severely 9) ___-damaged skin; however, it can occur in persons of any races. The prognosis for patients with CNH is 10) ___, although long-term morbidity is common. Spontaneous resolution is the exception; remissions may occur, but CNH usually continues unless adequately treated.
ANSWERS: 1) Greek; 2) ear; 3) men; 4) position; 5) vessels; 6) right; 7) hereditary; 8) females; 9) sun; 10) excellent
July 10, 2017Dermatology
According to an article published online in Nature Genetics (2 July 2017), mutations have been identified in a gene called CARD11 that lead to atopic dermatitis, or eczema, an allergic skin disease. The mutations were discovered in four unrelated families with severe atopic dermatitis, with subsequent identification of cell-signaling defects that contribute to allergic disease. Their findings also suggest that some of these defects potentially could be corrected by supplementation with the amino acid glutamine.
For the study, the authors analyzed the genetic sequences of patients with severe atopic dermatitis and identified eight individuals from four families with mutations in the CARD11 gene, which provides instructions for production of a cell-signaling protein of the same name. While some people with these mutations had other health issues, such as infections, others did not, implying that mutations in CARD11 could cause atopic dermatitis without leading to other medical issues often found in severe immune system syndromes. The authors next set out to understand how the newly discovered CARD11 mutations contribute to atopic dermatitis. Each of the four families had a distinct mutation that affected a different region of the CARD11 protein, but all the mutations had similar effects on T-cell signaling. With cell culture and other laboratory experiments, the authors determined that the mutations led to defective activation of two cell-signaling pathways, one of which typically is activated in part by glutamine. Then, growing cultured T cells from patients with CARD11 mutations with excess glutamine, boosted mTORC1 activation, a key part of one of the affected pathways. This suggested that the potential to partially correct the cell-signaling defects that may contribute to atopic dermatitis. The authors are now planning a study to assess the effect of supplemental glutamine and leucine, another amino acid that activates mTORC1, in people with atopic dermatitis with and without CARD11 mutations.
July 10, 2017Target Healthy Eating
1.5 pounds (more or less) red cabbage, sliced very thin on a mandolin
2 heaping Tablespoons fresh cilantro, very well chopped
3 Tablespoons your best extra virgin olive oil
2 Tablespoons, fresh lime juice
1 Pinch Salt, 1 pinch black pepper and 1 pinch chili flakes
1 cup pitted dates, coarsely chopped or sliced
8 ounces goat cheese, crumbled
2 or 3 fresh garlic cloves, mashed into the dressing
4 teaspoons well-toasted black sesame seeds
2 Tablespoons toasted flax seeds (optional toasting)
1. Do all your chopping, slicing, toasting, cutting first.
2. In the salad bowl you'll use for serving, add the olive oil, lime juice, pinch salt & black pepper, and with a fork, mash the two fresh garlic cloves. Also, add the chili flakes and with the fork, stir the dressing together.
3. Next, add all the cabbage and toss it so that every single piece of cabbage is covered with the dressing. Do this before you add anything else. It's extremely important to do this now and not later. If you don't cover each piece of cabbage now with the oil, the drier pieces will clump together and won't toss well later.
4. Next, add half of the chopped dates, half of the crumbled cheese, half of the cilantro, half of the flax and black sesame seeds and toss the dressed cabbage, slowly.
5. Finally, sprinkle the salad with the remaining dates, cheese, cilantro and sesame seeds and serve.
6. If you want this salad to be less crunchy, let it sit for a while and the cabbage will soften up a bit.
We were recently at Ralph Lauren's restaurant in midtown Manhattan, (East 50s, so, great for pre-theater dinner), and after ordering a salad, I asked about its wonderful crunch and learned that if you add some baked, very hard bread crumbs, pulverized in a food processor, to toasted black sesame seeds, you will get a pleasing crunch along with the flavor, that's very satisfying. Might want to try that with this salad recipe or others.
If you bought a mandolin, but it's turned into a dust gatherer, now you have an excellent reason to use it. There are certain tools that you cannot do without in a 21st Century kitchen, a mandolin is one of them and a food processor is another; a small kitchen scale also comes to mind.
In this colorful red cabbage salad, every one of the ingredients adds to the final extremely delicious flavor. I've experimented a lot with this recipe and you cannot omit any of these ingredients. I would even go so far as to say, don't even substitute. Wait until you're able to include all of them. If you don't have black sesame seeds, don't use white, order the black online. I get mine from Whole Foods, Amazon, FreshDirect and Nuts.com. All the other ingredients are readily available in an urban location. Considering, the extremely positive outcome, this is an easy recipe. Just a matter of following a few clear steps.
We saw a different type of play this weekend at one of our theater clubs, where we are patrons, the well known, Manhattan Theater Club, called: Cost of Living. There were two disabled characters (out of four actors) in this drama, played by two actors with those same disabilities. I liked having handicapped actors in those roles. During the play and before the curtain call, you could not tell whether or not the actors were disabled, or acting disabled. It was moving during curtain calls, to see that one young female actor, really had both legs amputated from the knees down, and appeared with her prosthetic legs. There were several themes in this play, certainly one was, who's in control, and being handicapped does not mean being out of control.
We had a long lazy stretch of a welcomed extended weekend and managed to stay out of the sun. Hope you were rested too.
From Our Table to Yours
July 10, 2017Regulatory
For our last Orphan Drug Designation Request, FDA told us that there could be a 6 month review time. We did contact the Division and were told about the major backlog.
As authorized under the Orphan Drug Act, the Orphan Drug Designation Program provides orphan status to drugs and biologics that are defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases, which are generally defined as diseases that affect fewer than 200,000 people in the United States. Orphan designation qualifies the sponsor of the drug for various development incentives, including tax credits for clinical trial costs, relief from prescription drug user fee if the indication is for a rare disease or condition, and eligibility for seven years of marketing exclusivity upon approval. A request for orphan designation is one step that can be taken in the drug development process and is different than the filing of a marketing application with the FDA.
The FDA has unveiled a strategic plan to eliminate the existing orphan designation request backlog and ensure continued timely response to all new requests for designation with firm deadlines. The agency's Orphan Drug Modernization Plan comes a week after FDA Commissioner Scott Gottlieb committed to eliminating the backlog within 90 days and responding to all new requests for designation within 90 days of receipt during his testimony before a Senate subcommittee.
Currently, the FDA has about 200 orphan drug designation requests that are pending review. The number of orphan drug designation requests has steadily increased over the past five years. In 2016, the FDA's Office of Orphan Products Development received 568 new requests for designation - more than double the number of requests received in 2012. The increased interest in the program is a positive development for those with rare diseases and under this new plan, the agency remains committed to advancing the program to ensure it can efficiently and adequately review these requests.
This is the first element of several efforts the FDA will undertake under its new Medical Innovation Development Plan, which is aimed at ensuring that the FDA's regulatory tools and policies are modern, risk based, and efficient. The goal of the plan is to seek ways the FDA can help facilitate the development of safe, effective and transformative medical innovations that have the potential to significantly impact disease and reduce overall health care costs. Among the elements of the plan to eliminate the backlog, the FDA will deploy a Backlog SWAT team comprised of senior, experienced reviewers with significant expertise in orphan drug designation. The team will focus solely on the backlogged applications, starting with the oldest requests. The agency will also employ a new streamlined Designation Review Template to increase consistency and efficiency of its reviews. The program will also look to collaborate within the agency's medical product centers to create greater efficiency, including conducting joint reviews with the Office of Pediatric Therapeutics to review rare pediatric disease designation requests.
To ensure all future requests receive a response within 90 days of receipt, the agency will take a multifaceted approach. These efforts include, among other new steps: reorganizing the review staff to maximize expertise and improve workload efficiencies; better leveraging the expertise across the FDA's medical product centers; and establishing a new FDA Orphan Products Council that will help address scientific and regulatory issues to ensure the agency is applying a consistent approach to regulating orphan drug products and reviewing designation requests.
The FDA intends to communicate around the successful elimination of the backlog by mid-September and will soon provide more information about the Medical Innovation Development Plan.
July 10, 2017Immunology
For years, the ocular surface was thought to be sterile because of the presence of an enzyme called lysozyme that destroys bacteria, antimicrobial peptides, and other factors that rid the eye of microbes that may land from the air (or from our fingers) onto the surface of the eye.
According to an article published in the journal Immunity (27 June 2017), a study has demonstrated the existence of a resident ocular microbiome that trains the developing immune system to fend off pathogens. And yes there is a resident microbe living on the surface of the eye that protects the cornea from infection. According to the authors, this is the first evidence that a bacterium can live for a long time on the ocular surface, and that this study addresses a longstanding question about whether there is a resident ocular microbiome.
For the study, the authors were able to culture bacteria from the mouse conjunctiva, the membrane that lines the eyelids, and they found several species of Staphylococci, which are commonly found on the skin, and Corynebacterium mastitidis (C. mast). However, it wasn't clear whether those microbes had just arrived on the eye and were en route to being destroyed, or whether they lived on the eye for extended periods of time. During the study, the authors found that C. mast, when cultured with immune cells from the conjunctiva, induced the production of interleukin (IL)-17, a signaling protein critical for host defense. Upon further investigation, they found that IL-17 was produced by gamma delta T cells, a type of immune cell found in mucosal tissues. IL-17 attracted other immune cells called neutrophils -- the most abundant type of white blood cell -- to the conjunctiva and induced the release of anti-microbial proteins into the tears. The authors are currently investigating the unique features that can make C. mast resistant to the immune response that it itself provokes and allow it to persist in the eye.
To determine whether the microbe was contributing to the immune response in mice, the authors formed two groups, one control (with C. mast) and one treated with an antibiotic to kill C. mast and other ocular bacteria, and then challenged them with the fungus, Candida albicans. The mice receiving antibiotics had a reduced immune response in their conjunctiva and were not able to eliminate C. albicans, leading to full-blown ocular infection. The control mice with normal C. mast on the other hand were able to fend off the fungus. The authors also noticed that mice from the NIH animal facility had C. mast on their eyes, but mice from the Jackson Laboratory (JAX) in Maine and other commercial vendors did not. This fortuitous observation allowed the authors to determine if C. mast was truly a resident microbe, as opposed to a transient microbe that lands on the eye from the environment. They did this by inoculating C. mast-free mice with the microbe and determining if the microbe could be cultured from those animals' eyes many weeks later. They also determined whether the microbe could easily be transmitted among cagemates. When inoculated with C. mast, JAX mice produced conjunctival gamma delta T cells that released IL-17. Bacteria could still be cultured from their eyes after many weeks. By contrast, several other strains of bacteria inoculated onto the eyes of JAX mice disappeared without inducing local immunity. Interestingly, C. mast was not spread to cage-mates even after eight weeks of co-housing; however, C. mast can be passed from mother to pup. Both of these observations support the notion that C. mast is a resident commensal, not a bacterium that is continually re-introduced to the eye from the skin or the environment.
According to the authors, although C. mast appears to stimulate a beneficial immune response, there may be situations in which it could cause disease. For example, the elderly tend to have suppressed immune systems, which might allow C. mast to grow out of control and cause disease. The authors are currently investigating whether other bacteria play a role in regulating eye immunity.
July 10, 2017History of Medicine
According to his biographer, Dr. J.D. Oriel, in his lifetime, Moritz Kaposi, MD, was acknowledged as one of the great masters of the Vienna School of Dermatology, a superb clinician and renowned teacher. While his mentor, Ferdinand von Hebra, is considered the father of dermatology, Kaposi was one of the first to establish dermatology on its anatomical pathology scientific basis. He became the chairman of the Vienna School of Dermatology, after Hebra's death in 1880.
Moritz Kaposi, a Hungarian physician, was born on 23 October 1837 in Kaposvar, Austria-Hungary and died on 6 March 1902 in Vienna. This well-known physician is best known as the dermatologist who discovered the skin tumor that received his name (Kaposi's sarcoma). Kaposi was born to a Jewish family, whose original surname was Kohn. But with his conversion to the Catholic faith, he changed it to Kaposi in 1871, in reference to his town of birth. One purported reason behind this is that he wanted to marry a daughter of current dermatology chairman, Ferdinand Ritter von Hebra, and advance in the society, which he could not have done being of Jewish faith. This seems unlikely because he married Martha Hebra and converted to Catholicism several years prior to changing his name, by which time he was already well established in the Vienna University faculty and a close associate of von Hebra. A more plausible explanation is based on his own comments to colleagues that he changed his name to avoid confusion with five other similarly named physicians on the Vienna faculty. Rumors about the sincerity of both his marriage and his concerns about his Jewish ancestry may have arisen through professional jealousy. According to William Dubreuilh (1857-1935), first professor and chairman of dermatology in Bordeaux: On disait de Kaposi qu'il avait pris la fille de Hebra, sa maison, sa chaire et sa clientele, laissant le reste a son beau-frere Hans Hebra. - It was said of Kaposi that he had taken the daughter of Hebra, his home, his chair and his clientele, leaving the rest to his brother-in-law, Hans Hebra.
In 1855, Kaposi began to study medicine at the University of Vienna and attained a doctorate in 1861. In his dissertation, titled Dermatologie und Syphilis (1866), he made an important contribution to the field. Kaposi was appointed as professor at the University of Vienna in 1875, and in 1881 he became a member of the board of the Vienna General Hospital and director of its clinic of skin diseases. Together with his mentor, Ferdinand Ritter von Hebra, he authored the book Lehrbuch der Hautkrankheiten (Textbook of Skin Diseases) in 1878. Kaposi's main work, however, was Pathologie und Therapie der Hautkrankheiten in Vorlesungen fur praktische Arzte und Studierende (Pathology and Therapy of the Skin Diseases in Lectures for Practical Physicians and Students), published in 1880, which became one of the most significant books in the history of dermatology, being translated to several languages. Kaposi is credited with the description of xeroderma pigmentosum, a rare genetic disorder now known to be caused by defects in nucleotide excision repair (Ueber Xeroderma pigmentosum. Medizinische Jahrbucher, Wien, 1882: 619-633). Among other diseases, Kaposi was the first to study Lichen scrofolosorum and Lupus erythematosus. In all, he published over 150 books and papers and is widely credited with advancing the use of pathologic examination in the diagnosis of dermatologic diseases.
Kaposi's name entered into the history of medicine in 1872, when he described for the first time Kaposi's sarcoma, a cancer of the skin, which he had discovered in five elderly male patients and which he initially named idiopathic multiple pigmented sarcoma. More than a century later, the appearance of this disease in young gay men in New York City, San Francisco and other coastal cities in the United States was one of the first indications that a new disease, now called AIDS, had appeared. In 1993, the discovery that Kaposi's sarcoma was associated with the herpesvirus, sparked considerable controversy and scientific in-fighting until sufficient data had been collected to show that indeed KSHV was the causative agent of Kaposi's sarcoma. The virus is now known to be a widespread infection of people living in sub-Saharan Africa; intermediate levels of infection occur in Mediterranean populations (including Israel, Saudi Arabia, Italy and Greece) and low levels of infection occur in most Northern European and North American populations. Kaposi's sarcoma is now the most commonly reported cancer in parts of sub-Saharan Africa. Kaposi's sarcoma is usually a localized tumor that can be treated either surgically or through local irradiation. Chemotherapy with drugs such as liposomal anthracyclines or paclitaxel may be used, particularly for invasive disease. Antiviral drugs, such as ganciclovir, that target the replication of herpesviruses such as KSHV have been used to successfully prevent development of Kaposi's sarcoma, although once the tumor develops these drugs are of little or no use.
June 26, 2017Neurology
NRXN1 and CNTN6 are important during brain development and produce molecules that help brain cells form connections with one another. In addition, the two genes are turned on in areas that are part of the cortico-striatal-thalamo-cortical circuit, a loop of brain cells connecting the cortex to specific regions involved in processing emotions and movement. While copy number variants in NRXN1 have been implicated in other neurological disorders including epilepsy and autism, this is the first time that scientists have linked copy number variants in CNTN6 to a specific disease, Tourette syndrome.
According to an article published online in Neuron(21 June 2017), structural changes have been identified in two genes that increase the risk of developing Tourette syndrome, a neurological disorder characterized by involuntary motor and vocal tics. Although involuntary tics are very common in children, they persist and worsen over time in people with Tourette syndrome. Tics associated with Tourette syndrome appear in children, peak during the early teenage years and often disappear in adulthood. Many people with Tourette syndrome experience other brain disorders including attention deficit disorder and obsessive-compulsive disorder.
For the study, genetic analyses were conducted on 2,434 individuals with Tourette syndrome and compared them to 4,093 controls, focusing on copy number variants, changes in the genetic code resulting in deletions or duplications in sections of genes. The results determined that deletions in the NRXN1 gene or duplications in the CNTN6 gene were each associated with an increased risk of Tourette syndrome. In the study, approximately 1 in 100 people with Tourette syndrome carried one of those genetic variants.
The authors are planning to take a closer look at the mutations using animal and cellular models, and more research is needed to learn about ways in which the genes contribute to development of Tourette syndrome and whether they may be potential therapeutic targets.
June 26, 2017What's New
We are back from the annual DIA meeting in Chicago, and it was quite a success. Our presentation on How eSource Solutions are Impacting Clinical Research Sites, Patients, Regulators and Drug and Device Companies, with Jonathan Helfgott and Mitchell Efros, was well-attended and quite stimulating.
Two-Striped Grasshopper - James Farley Photographer Par Excellence
For more information about Target Health contact Warren Pearlson (212-681-2100 ext. 165). For additional information about software tools for paperless clinical trials, please also feel free to contact Dr. Jules T. Mitchel. The Target Health software tools are designed to partner with both CROs and Sponsors.
Joyce Hays, Founder and Editor in Chief of On Target
Jules Mitchel, Editor
June 26, 2017History of Medicine
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.