Pregnancy paper picked by bio elite

A paper on pregnancy immunology from the lab of Dr. Doug Antczak has been selected by the Faculty of 1000, placing his work in a library of the top two percent of published articles in biology and medicine.

According to its website, the Faculty of 1000 (F1000) identifies and evaluates the most important articles in biology and medical research publications. Articles are selected by a peer-nominated global faculty composed of the world’s leading scientists and clinicians who rate chosen articles and explain their importance.

Antczak’s paper, “Functions of ectopically transplanted invasive horse trophoblast,” (Reproduction 2011 Mar. 9), was selected and evaluated by F1000 member Anthony Michael Carter.

“This paper advances understanding of how invasive trophoblast cells are able to establish endometrial cups in the mare,” wrote Carter in an evaluation describing Antczak’s discovery. Trophoblast cells, which form around embryos, can migrate to the uterus. In pregnant mares, these invading cells form ulcer-like structures in the uterus that produce equine gonadotropin. This hormone serves several functions in pregnancy including protecting the embryo from the mother’s immune system.
“Our work may have practical application in equine practice, for example in the development of new methods to prevent unwanted estrus in competition mares,” said Antczak. “It also has implications for biomedical use in the future, as a way to provide sustained delivery of biologically active molecules or drugs.”

The project’s lead scientist, Dr. Amanda de Mestre, was formerly a post-doctoral fellow in the Antczak lab, and is now a faculty member at the Royal Veterinary College in London. De Mestre’s training included two distinct experiences at Cornell. While still a veterinary student in her native Australia, she spent a summer conducting research in the Antczak lab as a participant in Cornell’s Leadership Program.

F1000’s database provides both a repository for peer-rated high-impact biology articles and a social media forum for serious science. Its community features enable discussions to be built around the selected publications. Additional faculty members may evaluate and rate the article, and subscribers can post comments. Antczak will be able to join the conversation, providing follow-up notes concerning his article and responding to ideas put forth by commenters and evaluators.
“As a post-publication peer review service, we embrace the idea that the impact of your article can deepen and spread in unforeseen ways with community interaction,” wrote Sarah Greene, Editor in Chief of the F1000, in a letter to Antczak announcing his inclusion. “Even your own reckoning of the article may advance toward further conclusions and result in new strategies and collaborations.”

This research is part of a continuing program in equine pregnancy immunology at the Baker Institute for Animal Health that has been supported for many years by the Zweig Memorial Fund, the Dorothy Russell Havemeyer Foundation, and the National Institutes of Health.

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Zweig News Capsule
No. 51, June 2011

Bloodstream battles

When bacteria bloom in the blood the ensuing battle can wreak havoc on the body. Endotoxemia, bacterial blood poisoning, ignites a rising tide of immune cells and blood platelets that help fight infection but can also cause tissue damage. In horses, endotoxemia and subsequent inflammation can cause severe complications following abdominal surgeries, in common equine disorders including colic and retained placenta, and in weak foals that fail to nurse properly.

Dr. Thomas Divers is leading a team of Cornell veterinarians investigating a new approach to treating the effects of endotoxemia by quelling the rampaging immune response. Collaborators Drs. Marjory Brooks, Susan Fubini, Ashlee Watts, Tracy Stokol, and Sally Ness aid in the investigation.

“Veterinary clinicians currently use a ‘best guess’ approach to managing horses with endotoxemia,” said Divers. “They typically administer a broad spectrum of treatments to clear bacteria and support cell repair, but specific attempts to block the inflammatory response have mostly failed.  We have developed a new strategy for treating endotoxin that targets blood platelets as a key control point.”

If successful, this novel approach will change the best-guess strategy into an evidence-based solution to suffering by using the anti-platelet drug clopidogrel (Plavix®), one of the most commonly used drugs in human medicine. The project will provide insights into the pathophysiology of endotoxemia and the ability of Plavix® to down-regulate platelet reactivity in endotoxic horses.
“Plavix® is a highly effective oral anti-platelet agent, and holds promise for helping treat inflamed horses,” said Divers. “We have optimized techniques to evaluate equine platelet reactivity, forming a testing panel broadly applicable for investigating thrombosis in horses, particularly in studying laminitis. We are now performing anti-platelet drug treatment trials for horses with endotoxemia. The trials are going well, and we are looking forward to publishing by the end of the year. When the patent on Plavix® expires in 2012, generic versions of the drug will become available, and we will be poised to start using anti-platelet drugs to affordably and effectively treat blood poisoning and inflammation in horses.”

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Zweig News Capsule
No. 51, June 2011

Cross-continental collaboration from farm to fork

dFood sustains us but also can endanger us. In the first major public health project between Cornell’s College of Veterinary Medicine and Weill Cornell Medical College-Qatar, a team of multidisciplinary cross-continental collaborators aims to mitigate food contamination and keep food clean, from production to consumption, in Qatar.

With a $1 million grant from the Qatar Research Foundation, Hussni Mohammed, professor of epidemiology at the Veterinary College, is leading a project to assess risks associated with food-poisoning pathogens. Drawing from a network of faculty and resources spanning the two campuses, Mohammed’s team will carry out risk assessment studies to model how pathogens put the public at risk in order to better inform efforts to control contamination.

“We are investigating the epidemiology and ecology of food-borne pathogens as they move through the food chain from the sources to the table in Qatar,” said Mohammed. “Four kinds of bacteria pose major threats to Qatar’s food systems: Escherichia coli, Salmonella, Campylobacter and Listeria monocytogenes. We aim to determine each species’ prevalence; to identify agent, host and environmental factors that perpetuate these pathogens; and to ascertain factors such as antibiotic resistance that could contribute to development of new virulent strains.”

fThis research will help answer questions crucial to addressing contamination. Does infected milk come from infected cows? Or are pathogens more likely to enter the food chain in the packaging facility, during transportation or at the retailers where milk is ultimately sold?

Following food from farm to table, Mohammed’s team investigates all levels of the supply chain, drawing samples from food animals, their products, the environments they pass through and the humans consuming them. Using bacteriological and PCR techniques to test for pathogens at each level, Mohammed is constructing data-driven mathematical models to determine where and how these pathogens infiltrate the food supply system.

“The models we develop will help producers and public agencies develop and implement cost-effective and science-based strategies to ensure the safety and sustainability of Qatar’s food supply system,” said Mohammed. “Taking our data a step further, we are using the samples from humans to search for ties between food-poisoning pathogens and inflammatory bowel disease (IBD). Little is known about IBD, but several studies suggest it is caused by bacterial imbalances in the gut. We hope our data can help elucidate correlations between these food-borne pathogens and IBD.”

He added: “Qatar is a quickly developing country committed to supporting new research through the Qatar Foundation. It is a privilege to be involved with a project in Qatar that could have life-changing applications for public health in the region and in the wider world.”

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Cornell Chronicle
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MyScience
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R&D Magazine
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USAgNet
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Scientific Computing
http://www.scimag.com/…

Ph.D student lands three fellowships in three months to combat nerve disorders

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In his effort to address the needs of underserved communities in health and education, Christopher Blackwood, a doctoral student in the area of pharmacology, has landed three major fellowship awards in three months to support his research into how the brain creates new neurons.

Blackwood hopes his work will contribute to new therapies for such neurodegenerative disorders as Alzheimer’s and Parkinson’s diseases, that disproportionately affect minority communities.

This year Blackwood was one of only 20 students across the nation to receive the prestigious Ford Dissertation Fellowship for 2011, which not only provides a stipend and travel expenses, but also opportunities to confer with former Ford fellows.

“Meeting the other current and former Ford fellows is an incredible opportunity to learn from my peers, exchange ideas and forge future partnerships,” said Blackwood.

Blackwood also has received the Cornell Provost’s Diversity Fellowship for 2011 and a Kirschstein research award to promote diversity in health-related research from the National Institutes of Health.

A first-generation minority college student, Blackwood was one of four children raised by a single mother in the Bronx, where economic and educational disparities regularly affected his life. After graduating from Clark Atlanta University, he came to Cornell’s Department of Biomedical Sciences in 2007 to study neurogenesis.

“Producing new neurons is critical to the function and development of the brain. I study how signaling pathways regulate this process,” said Blackwood. “This has important implications for neurodegenerative diseases, in which neurons are progressively lost. For example, by the year 2050, an estimated 150 million people will suffer from Alzheimer’s disease. If we could learn how to increase the production of neurons to compensate for dying brain cells, we may be able to provide new therapies. I hope my research can address health disparities such as neurodegenerative diseases that disproportionately affect marginalized communities.”

Committed to serving underrepresented communities in education as well as science, Blackwood has worked with Cornell’s Office of Minority Educational Affairs to hire undergraduate minority students in his lab. He has recruited several budding scientists, some of whom are already engaged in independent research.

f“The best science comes from diverse minds,” said Blackwood. “In the future I hope to apply my expertise to develop mentorship, recruitment and retention programs for underrepresented minority students. I feel blessed to pursue a Ph.D. at Cornell, to have the credentials to achieve these goals, to speak up about the factors that are detrimental to success and to use my research and teaching to potentially remedy destructive diseases.”

Blackwood’s latest award, from the University of California-San Francisco, will send him to their two-day “Postdoc Bootcamp” in June to learn how to navigate the next tier of a typical research career. The selective workshop for faculty-nominated Ph.D. students in the life sciences will cover strategies for finding postdoctoral positions and keeping a career on track.

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Cornell Chronicle
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R&D Magazine
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ECN Magazine
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Scientific Computing
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Dissolving diseases

International dog disease expert eliminated ailments across species and the world

“I started at James Baker’s lab under a challenge,” said Leland ‘Skip’ Carmichael, PhD ’56. “I came in his office looking for graduate work. He told me I had six months to figure out how a dog’s immune system responds to canine hepatitis, or I was out.”

Fortunately for dogs across the world, Carmichael passed the test. Over the 40 years he spent at Baker Institute he became one of the world’s best-known international authorities on canine infectious diseases. He has characterized, developed tests and treatment plans for, and invented vaccines against most major canine infectious and reproductive diseases, including distemper, hepatitis, canine parvovirus-2, canine herpesvirus, and canine brucellosis.

“We were at a time when diseases were being recognized and their causes clarified,” said Carmichael. “We focused on research that could directly benefit animals, and always saw our problems in the field.”

From the field to the lab, Carmichael exercised an aptitude for innovation in eradicating disease. “Baker Institute was one of the first labs to use tissue culture methods to isolate viruses, look for vaccines, develop serological tests, and measure immune responses,” said Carmichael. “When a mysterious disease began causing widespread abortions in dogs across the nation, I was charged with figuring out why. By air delivery at midnight I received a paint can that contained aborted fetuses and placental tissue. I went straight to the lab and inoculated plates with tissue samples.  The next morning the plates had bloomed with bacteria I’d never seen before.”

Carmichael had found a new species of Brucella, bacteria causing a devastating venereal disease best known for killing farm animals and harming humans who consume infected raw milk.

“Brucellosis is one of the most important veterinary diseases. We were the first to recognize the canine strain and establish control. We offered a free testing service, and fielded over 10,000 phone calls in the first year. Now Cornell’s Animal Health and Diagnostic Center runs the most reliably accurate Brucellosis test I know. The disease has all but disappeared in dogs.”

Today, canine infectious diseases are much rarer than when Carmichael first stepped into Baker’s office, in part because of the work he and his colleagues at Baker Institute have done. Meanwhile, his educational legacy continues. Carmichael’s former graduate student Collin Parish now directs Baker Institute.

“Dogs are part of the human experience,” said Carmichael, “but we’ve seen a nation-wide diminution of canine research in recent years. Most funding comes from institutions that favor research modeling human disease. Baker believed that veterinary research should focus on diseases of animals, I was fortunate to work in a time when that goal garnered strong support. I hope this institute will continue conducting research that can help dogs in the future.”

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‘Scopes Magazine
July 2011

Breaching barriers, reaching remedies

Unlocking new treatment potential for major diseases from MS to Alzheimer’s to HIV

In her first few years at Cornell, Dr. Margaret Bynoe rocked the world of immunology with major advances that are already changing how diseases are treated. Some were so unconventional that it took time to convince her peers they could work. “I’ve been told things couldn’t be done,” said Bynoe, “and that I was only ‘challenging dogma.’ But that’s how science builds knowledge.”

Bynoe knew she was on to something when she developed a novel treatment for multiple sclerosis (MS) in mice, an auto-immune disease that affects the nervous system.

“The immune system is like a child,” she said. “It learns as it matures. If it learns improperly it starts attacking the body. In MS it targets myelin, the protective coating insulating nerves.  To stop this we need a way to reeducate an adult immune system.”

Old dogs struggle with new tricks, but they are less likely to attack friends when they are properly introduced. Bynoe created patches soaked in myelin, applying  them to the skin of mice genetically predisposed to MS. “Their immune systems learned to recognize myelin as friend, not foe. We successfully abolished the disease.”

When she submitted a grant to develop this technique into a human treatment, reviewers said it would never work. Several years later, Bynoe’s work inspired a group of Polish researchers to use her technique on humans, significantly reducing symptoms in 80% of MS patients in their trial.

The ability to re-imagine paradigms helped Bynoe discover another new technique with the potential to shape the course of treatments for MS and other major neurological ailments.

“While investigating Adenosine, a crucial compound in many bodily processes, we discovered that it regulates the blood-brain barrier, which prevents most immune cells and foreign substances from entering the brain,” she said.

On the bloodstream highway, the brain is a restricted exit, but sometimes pathogenic particles sneak through its molecular gate.

“Diseases that infiltrate the brain become difficult to treat. If we could regulate the barrier safely we could put a damper on diseases like Alzheimer’s, cancer, and HIV-AIDS, by delivering drugs directly to afflicted cells. We could also potentially close the gate to stop rogue immune responses like those that cause MS.  Adenosine seems to be the gatekeeper. We think we have the key.”

Using caffeine to block Adenosine from opening the gate to immune cells, Bynoe stopped MS-like symptoms in mice. Her lab’s next goal is to use Adenosine to get treatments past the barrier in mice with Alzheimer’s. Using various models in collaboration with other scientists, they plan to investigate barrier-breaching treatments that could one day tackle HIV-AIDS.

“It took over a year of rigorous experimentation to confirm it works,” said Bynoe. “Now we hope to expand to treating larger animals.”
Partnering with entrepreneurs and investors, Bynoe helped found a growing company driven by her research. They are currently working to develop tools that will treat a wide array of human neurologic diseases.

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‘Scopes Magazine
July 2011

Keeping your organs in shape

Life on the faculty fast track leads to new developmental discoveries

One of the College’s youngest faculty, precocious Polish immigrant Natasza Kurpios kicked off her Cornell career earlier than most.

 

“We met by chance at a conference in Barcelona,” said Dr. Ruth Collins, professor in the Department of Molecular Medicine. “She had recently started as a post-doc at Harvard and was presenting a poster on her work that was attracting a lot of buzz in the field. Inspired by her talent and potential, I encouraged her to apply to our department. Her interview confirmed how well her research aligned with the department’s established strength in signal transduction, and her boundless energy and infectious enthusiasm made it clear she would be an outstanding teacher and colleague.”

 

The department offered Kurpios a faculty position, allowing time to complete her work at Harvard. There she discovered the first vertebrate example linking changes in organ development to changes at the level of individual cell shapes. Now she is expanding this work while leveraging the College’s diversity of animal systems in avian and mammalian species.

 

“We investigate how cells change shape to form organs, and the genes regulating this process,” said Kurpios. “On the outside most animals look symmetrical. On the inside it’s a different story. The heart and stomach are on the left, the liver is on the right, intestines loop and coil from left to right in just the right shape to fit in the body.

“Organs growing in the wrong direction or the wrong place cause problems. For example, in babies born with a birth defect called ‘gut malrotation’, incorrectly looped intestines tie themselves in knots, compromising digestion and blocking off their own blood supply. We knew this was controlled by genes but no one knew which genes were responsible.”

Looking through windows she made in chicken eggs to study developing embryos, Kurpios discovered the key gene regulating intestine looping: PITX2.

“This gene is like the conductor of a vast orchestra, setting off a cascade of signals telling other genes how to build organs. All species have this gene on the left side of the body. If it ends up on the wrong side, the organ map shifts and the intestines loop improperly.”

This discovery shed light on how gut malformations can develop. “We are looking into the potential role of PITX2 in this and other bowel obstruction issues, such as gastric dilatation and volvulus, that commonly afflict dogs and horses as well as humans,” said Kurpios.

Actively engaged with peers in the Vertebrate Genomics Group and the Cornell Stem Cell Program, Kurpios also collaborates with computational biologists and bioengineers across campus to model developmental changes and analyze the mechanical properties of tissue matrices influencing organ growth.

 

“These are fundamental biological questions with enormous applicability to stem cell biology and cancer studies,” said Collins. “Kurpios’s hiring reflects the goals of New Life Science initiative in strengthening key research areas and recruiting faculty to work across disciplinary boundaries.”

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‘Scopes Magazine
July 2011

Seeking the next generation

The time is ripe for hiring new faculty as retirement numbers swell

The tide is rising in our faculty pool as the average age of professors in the College continues to climb. Demographic shifts reveal a troubling trend as an oncoming wave of retirement threatens to leave a human deficit in its wake. As the College races to find new talent to fill the impending gap, it faces an unprecedented opportunity to shape the course of its future for years to come.

“The faculty body is healthy when it has a balanced age demographic,” said Judy Appleton, Associate Dean of Academic Affairs in charge of academic appointments at the College. “To maintain a healthy dynamic we need to maintain continual intake. During my first year as Associate Dean in 2007 only one person retired. This year four will retire. It’s the beginning of a wave.”

A demographic swell has been building across the University since a brief hiring boom in the late 1980s. Since then the proportion of University professors aged 55 and above has doubled from 25% in 1982 to 50% in 2010. Numbers at the College climbed even more sharply, from 21% then to today’s unprecedented 57%. For the University and especially for the College, hiring strong new faculty has become more crucial than ever before.

“This is the perfect time to strengthen our faculty base,” said Appleton. “It’s a buyer’s market in the wake of the recession. Universities haven’t been hiring, there’s a backlog of post-docs searching for positions creating an extremely competitive pool. At the same time, we are competing with other universities in the same situation, vying to attract the cream of the crop.”

This year the College embarked on three new faculty searches for positions in the Department of Clinical Sciences. Each position attracted between 140 and 190 applications. According to Appleton, the applications were extraordinary, and competition with other universities grew heated as we bid for the best of the best.

“Recruitment in the sciences is extremely expensive,” said Appleton. “A new researcher needs significant startup funds to establish a lab, buy equipment, and hire students and assistants. Finding startup funds is our most significant challenge. The rest of the university is trying to hire pre-fills in anticipation of retirements. Because of high startup costs in our field, it’s all we can do to keep up with retirements as they come.”

This summer, department chairs across the College will convene to form a “five-year faculty needs forecast”.  They will determine the College’s hiring needs, set up search committees, post positions, and interview this fall. Next fall will see a new incoming class of College faculty that will shape the next generation of our academic leaders.

“This will be the most important thing we do,” said Appleton. “It is a great responsibility, and very challenging in the current financial climate. It is also a fantastic opportunity that will set the course of the veterinary college for the next 100 years.”

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‘Scopes Magazine
July 2011

The Francis H. Fox Scholarship

How Fox’s friends and former students gave the prankster his best surprise yet

What comes to mind when you think of Francis H. Fox? If you were one of the legions he trained, you might remember lively lectures offset by mischievous humor, or rolling up farm roads for firsthand lessons in large animal medicine. Perhaps you’ve only heard his name in the College’s legends: rumors of preternatural diagnostic powers, or elaborate pranks exchanged with students. If you’ve ever driven down Route 366 near the College, you may think of his name in white paint, infamously emblazoned on the side of an old bridge over the road and accompanied by a public birthday counter.

This symbol has become a lasting tribute to the strong bonds between one of the College’s most well-known professors and the generation of veterinary students he trained, challenged, inspired, and befriended. That close camaraderie roused a large group of Fox’s former students and fast friends to unite and establish a scholarship in his honor, gathering supporters happy to give their mentor a legacy that would continue his passion for helping veterinary students for years to come.

“When I was a student I spent a lot of extra time with Dr. Fox,” said Dr. Pete Malnati ’52, who spearheaded the project. “He would call up interested students to go out on special cases with him. He was an exceptionally committed teacher, happy to share his knowledge and experience and sense of humor. I appreciated what he did for me, and for my fellow students, and we wanted to give back.”

The Friends of Francis Fox had no trouble getting support from enthusiastic peers. More than 200 people contributed over $22,000 in the first year alone. When Fox entered the Centennial New York State Veterinary Medical Society meeting in Rochester, NY in Fall 1990, he was surprised with a formal announcement establishing the endowment in his name.

“We are honoring Dr. Fox for his contributions to veterinary medicine in the field of large animal medicine and ophthalmology, especially as a teacher, clinician, and advocate of the art of physical diagnosis,” said Malnati. “He has given many of us this basic foundation in veterinary medicine. Thus we owe him this measure of gratitude as a friend, teacher, and fellow veterinarian.”

The selection criteria reflect Fox’s interests and ideals, seeking students highly motivated to serve the large animal sector, and those showing a gift mirroring Fox’s famous talent for physical diagnosis.

“It was all done behind my back,” said Fox. “I never expected such a thing, and felt very humbled. I hope it will help students who love the profession, and feel a calling to medicine because of their love of animals and satisfaction in working with them.”

The Francis H. Fox Scholarship fund has grown substantially since its inception in 1990, with continual support from hundreds of contributors. It aids two to four students in need a year, and has supported a total of 29 to date. Should you have interest in contributing to the Francis H. Fox Scholarship, please contact Amy Robinson in the Alumni Affairs and Development Office at amy.robinson@cornell.edu or (607) 253-3742.


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‘Scopes Magazine
July 2011

Common parasite uncovers key cause of Crohn’s disease

A single human lymphocyte, a white blood cell that acts as part of the immune system. Intraepithelial lymphocytes, which specialize in patrolling intestinal walls, can cause human Crohn's disease.

Immune systems have their sinister side, especially when they have not learned how hard to fight. Crohn’s disease and other inflammatory bowel diseases inflict more than a million Americans with debilitating pain and digestive unrest because of uncontrolled immune responses in the gut.

How this happens remained a mystery until immunologists at Cornell’s College of Veterinary Medicine caught a key culprit in Crohn’s disease: a cell from our own immune forces. With unconventional help from a common parasite, Eric Denkers, professor of immunology, and research associate Charlotte Egan identified a renegade cell responsible for this largely arcane and increasingly prevalent illness.

“Auto-immune diseases are on the rise in this country but their causes have remained largely unknown,” said Denkers. “It’s possible that these diseases are more common in the West because we’re too clean. Exposure to germs trains immune systems how to respond to threats. Early protection from germs may contribute to the increasing prevalence of immune system overreactions in our population, leading to auto-immune problems like allergies and inflammatory bowel disease.”

Similar symptoms arise when some hosts first face the prevalent protozoan Toxoplasma gondii. Denkers’ lab studies this parasite’s arsenal of host-manipulating powers, but recently they have steered Toxoplasma research in an entirely new direction.

Intestinal wall after Toxoplasma infection and inflammation, compared to undamaged intestinal wall.

“We noticed that the initial intestinal inflammation these parasites can cause looks very similar to what happens during Crohn’s disease,” said Denkers, one of the first to study this connection. “Our lab has started using Toxoplasma to model Crohn’s disease in humans and help us find the pivotal perpetrator, which has turned out to be a cell from our own immune forces.”

Specialized immune cells called intraepithelial lymphocytes patrol intestinal walls. Upon encountering invaders, they release messenger proteins that call more immune cells to the battleground. “Too many messenger proteins recruit too many immune cells, causing inflammation that can devastate the host’s own tissue,” Denkers explained. “Bad balance between good bacteria, bad bacteria, and immune interactions like inflammation cause Crohn’s disease.”

“For the first time we’ve discovered how infection can turn these immune cells pathogenic, stimulating them to cause disease, inflammation and necrosis in the small intestine,” said Denkers. “This marks a major leap toward understanding human Crohn’s disease. Unveiling this kind of immunological interplay may lead to improved prevention and care in an array of auto-immune diseases.”

Denkers and colleagues published their discovery in Mucosal Immunology, followed by a review article discussing Toxoplasma infection as a model for Crohn’s disease in the Journal of Biomedicine and Biotechnology in 2010.

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Cornell Chronicle, February 22, 2011
http://www.news.cornell.edu/…

Scientific Computing, February 23, 2011
http://www.scientificcomputing.com/…

PhysOrg
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R&D Magazine
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myScience
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Press Connects
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The Ithaca Journal
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