Monthly Archives: February 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
http://www.physorg.com/…

R&D Magazine
http://www.rdmag.com/…

myScience
http://www.myscience.us/…

Press Connects
http://www.pressconnects.com/

The Ithaca Journal
http://www.theithacajournal.com/

Training future leaders in diagnostics

Graduation rarely means the end of education, especially in the medical world. A veterinary degree opens doors to countless further training opportunities. The College of Veterinary Medicine and the AHDC offer residency programs that let DVMs delve into in the cellular side of disease. In the residencies for Diagnostic Sciences and Clinical Pathology, veterinarians wanting to gain more experience in diagnostics come to Cornell to practice for three years under the mentorship of seasoned specialists before testing to become board-certified specialists themselves.

Residency in Diagnostic Sciences

Wonhee Cha pioneers the nation’s first veterinary residency program in diagnostic sciences here at the AHDC. With a collection of experience in international clinical service and epidemiology research under her belt, she is honing her diagnostic tools in preparation for a future foray facing infectious diseases of the third world.

After earning her DVM from Kon-kuk University in Korea, Cha volunteered in Tanzania for two years as a public veterinarian. “The entire country has just one veterinary school and about 250 registered veterinarians,” says Cha. “Everywhere I turned, people and their animals needed help. One day I would be stitching up dogs or helping breed livestock, the next I would be educating farmers about husbandry techniques, or working on my biggest project establishing Tanzania’s first x-ray-capable veterinary center.”

Cha’s commitment to international veterinary fieldwork blossomed during her tenure in Tanzania. “When I visited villages to vaccinate chickens against New Castle Virus, I began to see just how vital their animals’ health was to their livelihood. People relied on their chickens for eggs, meat, and trade. Any infectious outbreak could be devastating.”

When the service period ended, Cha went on to pursue her burgeoning interest in epidemiology at the laboratory of infectious diseases and molecular biology at Ohio State University, where she earned her master’s degree.

“I was studying ways of detecting and differentiating types of the Avian Influenza virus,” says Cha, “and I began to realize how important it is to have good diagnostic tools. Without accurate diagnostics, you can never hope to study any epidemic. I wanted to learn these tools in a clinical setting.”

So Cha came to the College of Veterinary Medicine in 2008 to learn the diagnostic tools she needed, and to apply them to hands-on disease research at the College’s integrated hospital and diagnostic lab. As the solitary inaugural resident in the country’s first diagnostic sciences residency program, Cha is paving the way for the future of the field.

“We need more people who can do veterinary diagnostic work,” says Dr. Craig Altier, microbiologist at the AHDC and supervisor of the innovative position. “Most of us got our experience on the job. We were starting to worry about what will happen as we grow older. There are very few diagnostics training programs and it’s hard for a young person to get involved. So we worked to develop this new kind of residency.”

While other diagnostic residencies focus on a single area from the start, residents in this program spend the first year rotating through each of the AHDC’s thirteen sections, gaining an understanding of each diagnostic area and a comprehensive look at the field as a whole. In her first year Cha spent time in each section, including anatomical pathology, avian disease, bacteriology, clinical pathology, comparative coagulation, serology and immunology, endocrinology, molecular diagnostics, parasitology, quality milk production services, toxicology, virology, and veterinary support services.

“This is the only program that gives such an expansive overview, and that allows veterinarians to choose between different diagnostic specialties,” says Altier. “We want to train students who will become leaders in the field, with a broad enough scope that they could one day actually run a diagnostic laboratory.”

Following a year of rotations, Cha settled into the section of bacteriology, where she does a combination of fieldwork and research studying bacteria in dairy cattle of the New York State watershed. “Everyone is my teacher,” says Cha. “I’m surrounded by a wealth of knowledge and experience, from the technicians to the faculty, everyone has so much to teach. I feel humbler every day.”

In her third and final year, Cha continues her work in bacteriology, hoping to finish her PhD before setting out to pursue her dream of addressing infectious diseases of animals in developing countries.

Residency Program in Clinical Pathology

Sometimes you can look at an animal and know what’s wrong, but many mysteries of disease lurk far beneath the surface, in the cells themselves.

Clinical pathology residents Drs. Nora Springer and Erika Gruber ’06 are scientific sleuths who traded magnifying glasses for microscopes, investigating samples on the biochemical and cellular levels to study and diagnose disease.

“We deal with swabs, smears, and samples from almost any fluid or part of the body,” says Springer, who spent several years testing samples as a licensed veterinary technician before earning her DVM at Kansas State in 2008 followed by a small-animal internship at Louisiana State University. “This includes blood, urine, bone marrow, tumor cells, anything that could give cellular or chemical clues.”

Clues can come from all kinds of cells, and part of a clinical pathologist’s job is to recognize what is normal and what is not from each sort of sample. When a sample comes in, the clinical pathology residents provide the front line of investigation. After inspecting, describing, and forming a diagnosis, they consult with the lab’s board-certified pathologists, Drs. Tracy Stokol, Heather Priest, and Deanna Schaefer, who look over the report and discuss it with the residents.

Unlike most pathology programs, the discussion doesn’t stop there. Cornell’s program encourages collaboration, and all five staff dedicated to clinical pathology pool their perspectives three times a week.

“I chose Cornell because of the program’s strong structure and unique team-oriented approach,” says Springer, who is in her second year of the three-year residency. “This is the only program I’ve found where residents and clinical pathologists regularly meet to discuss cases as a group. Most programs have each resident meet with one mentor. At Cornell two residents and three clinical pathologists all meet together to review cases, investigate archived slides, or practice describing and diagnosing ‘mystery slides’ with interesting quirks we can learn from. It gives us a very well-rounded experience.”

“You gain a lot by hearing different opinions from people trained in different environments,” says Stokol, one of the three clinical pathologists who supervise the program. “Our residents must do a rotation in anatomic pathology, and can also choose to rotate through other specialties, including oncology, toxicology, and large or small animal medicine. That’s been very helpful for them.”Clinical pathology residents divide time between clinical service and research, exposing them to both sides of the field.

“Cornell has a rich history and philosophy regarding research,” says Stokol. “We expect our residents to complete a research project. We want to invest in them the intellectual curiosity of asking ‘why is this happening’ and ‘how can I test that?’ Residents challenging you is part of the fun. It makes you think about what you know. Is it based on true evidence or is it just something your teacher told you? It’s good to challenge the status quo, that’s how you learn new things.”

“This program drew me because it’s so well-rounded, emphasizing the diagnostic aspects of both research and clinical work,” says Gruber, a first-year resident and Cornell alum who returned after a small-animal internship at Colorado State followed by three years of veterinary relief work. “Residents also take an active teaching role, which I particularly enjoy. We help with labs in blocks, give special lectures, and guide students through their pathology rotations.”

At the end of their three years of service, Gruber and Springer will apply their knowledge in a three-day examination for board certification in clinical pathology. Several career paths branch out for a newly ordained clinical pathologist.  Some go on in academia, pursuing PhDs and becoming tenure-track research professors or joining a clinical track emphasizing teaching and service. Others go into diagnostic practice in labs like the AHDC, or into private industry, particularly in the field of pharmaceuticals. The government offers further jobs for trained clinical pathologists.

“We need people who can spread their knowledge and educate the next generation,” says Stokol. “We need future professionals who can encourage young people like Nora and Erika to go on in clinical pathology. The ultimate goal of academics is training our replacements. This is a challenging and rewarding field, and it’s a pleasure to work with people who share your passion.”

Learning genes to label germs

Genetic comparison can identify mystery pathogens

Organisms from all corners of the animal world arrive at the doors of the New York State Veterinary Diagnostic Laboratory and Animal Health Diagnostic Center (AHDC). Foreign or familiar, prevalent or peculiar, pathogens must reveal their true identities before veterinarians can begin to make sense of samples, diagnose diseases, and develop treatment plans.

How do you identify a microscopic organism? The traditional method has guided doctors and scientists through the past 100 years. Smear a sample on an agar plate, a petri dish covered with gelatin made from seaweed, and study the culture as it grows. What shape does it take? Does it move or stay still? What is its biochemical profile? What food does it prefer? Scientists use these kinds of questions to match mystery organisms to those successfully identified in the past.

But sometimes matching lists of characteristics isn’t enough.

“We deal with some oddball organisms,” says Dr. Craig Altier, a microbiologist with big aspirations for the future of identifying small life-forms.  While traditional methods of identification can reliably distinguish common or easily differentiated organisms, they shed less light on outliers, including newly mutated species, rare breeds of bacteria, and fraudulent fungi.

“Fungi look very similar under a microscope, and often biochemical differences between species prove undetectable,” says Altier. “We really needed a better way to tell such species apart. So when physical characteristics failed, we turned to genetics.”

Every individual has a unique DNA fingerprint, and so does every species. Evolution shakes the genetic dice many times over, but all species have certain genes that survive unchanged for generations.

“These highly conserved genes usually code for essential functional elements that would not work if they were changed, such as proteins required for basic cellular function,” says Altier. “They don’t vary much between individuals, but they do vary across species. We can use these genes to accurately identify organisms.”

Researchers have already been looking at conserved genes to map out relationships between species, and now Altier and his colleagues are adapting these techniques for veterinary medicine.

“We have finally reached a point where we can use these tools quickly and efficiently enough to diagnose disease,” says Altier. “Human medicine will benefit as well, but the technique is most valuable in veterinary medicine because there are so many different species of host animals and pathogens.”

The new approach uses PCR techniques to amplify DNA from selected conserved genes. Cornell’s on-campus DNA Sequencing Center decodes samples into a string of about 500 bases of A, T, C, or G, then compares them to samples in the National Center for Biotechnology Information’s genetic database to look for similarities.

The technique is already revolutionizing diagnostics, revealing relationships that could never have been found before. “One day we received a swab from the flipper of a sick sea lion,” says Altier. “We had no idea what kind of organisms might live there, but we found the answer quickly through DNA sequencing and a quick genetic comparison. We couldn’t have done that without this database.”

Genetic comparison tools raise the bar for diagnostic accuracy. “With the old methods we frequently got stuck saying one organism is ‘like’ another,” says Altier. “Now we can usually hone in on a more exact label. We match sequences down to the letter to find efficient, accurate diagnoses.”

Comparative genetics can also expand our knowledge of a given disease.

“We may find the same kinds of pathogens in different animals we never knew could host them, or on the same host species but at a different body site,” says Altier. “These techniques have already shed new light on how organisms evolve and how different species are related. We may soon begin discovering new important pathogens previously left unnoticed.”

Even unidentified organisms could prove priceless down the road. Many currently unidentified sequences float nameless through the database waiting to be compared. “When enough of these orphans begin to match,” says Altier, “we will begin to discover new disease-causing agents.”

Fund established for Expanding Horizons

Grants give students veterinary experience in developing nations

“Working abroad can change your life,” says Dr. Ton Schat, an avian pathology professor whose veterinary adventures abroad helped forge a fruitful career. “That kind of eye-opening experience affects all the people and animals you help as a veterinarian and shapes the kind of person you become.”

He hails from Holland, battled bacteria in Nigeria, launched labs against Marek’s disease in Mexico, and recently returned from an Australian excursion studying one of the more dangerous strains of Avian Influenza. With Cornell as his home-base since 1975, he has continued collaborations with researchers around the world. Best known for his industry-changing work improving poultry health for which he recently received a lifetime achievement award, Schat attributes the inspiration and success of his career to his early experiences abroad.

“I knew early on that I wanted to pursue international development,” says Schat, who earned his DVM degree from the State University of Utrecht in the Netherlands. “During my final and practical year of my studies in Utrecht  I went to Northern Nigeria on a fellowship to study causes of infertility in Fulani cattle. I really enjoyed my months there, from the hands-on work to interacting with the Nigerian students.”

Schat returned from Nigeria determined to pursue international work before going to graduate school. “I landed a job through the Dutch government to work on Marek’s disease in Mexico. I arrived in 1971 and worked there for four years, setting up a lab, training Mexican researchers, and working towards a vaccine.”

In Mexico, Schat met Dr. Bruce Calnek, an avian pathology professor from Cornell who shared Schat’s growing interest in Marek’s disease. Calnek invited Schat to work in his lab as a graduate student, and Schat has worked at Cornell ever since. While pursuing his PhD, Schat isolated the SB-1 strain of Marek’s disease in chickens and used it to develop a vital vaccine still used on the market today. The vaccine generated significant royalties for the College, and continues to generate income.

Most of that money went back to the former Department of Avian and Aquatic Animal Medicine, pooling with other departmental money to support grad students and research expenses. When the department later merged into the Department of Microbiology and Immunology and the flock of avian medicine students pursuing PhDs thinned, the money lay dormant for many years.

“Dr. Calnek was in charge of the former department’s funds. When he retired in 1996 I was charged with overseeing their use,” Schat explains. The Expanding Horizons program seemed like the perfect choice for Schat, who shares its core philosophy: that working in developing nations empowers students to improve themselves and their world.

Expanding Horizons provides Cornell veterinary students with grants to spend 6-10 weeks in a developing nation engaged in a hands-on veterinary experience or research project. Projects span the veterinary spectrum, from rehabilitating wildlife or teaching farmers vaccination techniques, to researching rhino parasites or promoting habitat conservation. Students have traveled to all corners of the world, including Kenya, Madagascar, Honduras, Bolivia, Italy, Vietnam, Thailand, Taiwan, and many more.

“More students are growing a keen interest in reaching out to the world around them,” says Schat, who teaches a biannual course in international veterinary medicine that has grown to an average class size of 60 students. “For most students who have gotten the chance to go abroad, it has opened their eyes and broadened their perspectives. My own time abroad was crucial to my personal development. I feel it is extremely important for our students to be able to have the same kind of experience that was for me so life-changing.”

“Since the program began in 1985, we have been able to support five to ten students a year,” says Jai Sweet, Director of student Services and multicultural Affairs who oversees the program. “This new fund sets the foundation for a steady, stable stream of support that will ensure more students can continue to pursue these extraordinary international opportunities.”

Should you have an interest in contributing to this fund, please contact Amy Robinson in the Alumni Affairs and Development Office at amy.robinson@cornell.edu or 607.253.3742.

Looking through the window

Clinical pathology bridges animals and answers

 “Blood is the window to the body,” says Dr. Tracy Stokol, a professor with a passion for pathology puzzles. Microscopic magnification opens that window, revealing a cellular world which veterinarians explore in the quest to analyze disease. Clinical pathologists like Stokol navigate that world as diagnostic detectives, using cellular samples from body tissue and fluids to piece together a patient’s story.

If an animal has a bodily bump, how do you tell if it’s a bruise or inflammation, a fatty tumor or malignant cancer? Veterinarians use needles to take samples for examination. Clinical pathologists use these cellular clues to solve medical mysteries.

“It’s critical for veterinarians to know clinical pathology because they use it every single day,” says Stokol. “Sick animals can’t tell you what’s wrong. Samples speak for the animals and clinical pathology translates. It’s a bridge between the animal and the answer.”

Body fluids can reveal much of what goes on inside an animal’s body. “Blood can tell you why a joint is swelling, expose cancer cells, or show abnormalities that indicate underlying liver disease,” illustrates Stokol. “We also work with bone marrow aspirates, samples from lymph nodes, cerebrospinal fluids, anything you can put a needle into and take a sample of could give an important clue.”

Stokol has taught the visual language of cellular samples at the College of Veterinary Medicine since 1993, and is now an associate professor in the Department of Population Medicine and Diagnostic Sciences. A skilled specialist, Stokol attributes her passion for clinical pathology to the fun of solving a mystery.

“I like a challenge,” says Stokol with steady eyes that have faced plenty of challenge in the microscopic realm. “I’m always intrigued by difficult cases and love figuring things out. Clinical pathology is a very visual field. You’re seeing interesting changes that are visually fascinating. It’s fun to look at things, but it’s also about putting pieces of information together to make a story.”

Stokol’s story started in Melbourne, Australia, where she earned her veterinary degree in 1987, worked for two years as an assistant veterinarian, and earned a PhD before coming to Cornell. She belongs to several societies for clinical pathology, chemistry, and diagnostics, and has published several book chapters and over 50 papers in peer-reviewed journals, reflecting her dedication to furthering research in her field.

“Research stimulates a kind of intellectualism you don’t get from puzzling out a case. It’s an entirely different way of thinking,” explains Stokol. “A lot of what we do in clinical work is memorizing facts and recognizing patterns. Research lets you ask more kinds of questions, it makes you think ahead and plan, and learn to deal with things that don’t work out the first time.”

That’s why Stokol and her colleagues require that the College’s clinical pathology residents complete a research project.

“Working in an academic environment, we need to advance the knowledge of our field. We have to continue to grow and understand more about the diseases we’re working with and the only way to do that is through research.”

As an academic clinician, Stokol furthers her passion through her teaching. Together with fellow clinical pathologists Dr. Heather Priest and Dr. Diana Schaefer, Stokol supervises the College’s residency program in clinical pathology.

“We need academic clinical pathologists to keep advancing the field and to keep it alive. Fewer people go into clinical pathology because there are fewer residencies available. We’re graduating fewer people, so fewer people are trained.”

Specialists in this field need thorough training to learn to successfully sort out the secrets cells can tell. But for Stokol and her peers, the challenge is worth it.

“One of the job’s biggest appeals is the instant gratification, knowing that you’re making a difference,” Stokol says. “Clinical pathology gets rapid results that help animals and their owners almost immediately. You’re giving vital information that a veterinarian can use to decide how to manage or treat a patient, or helping an owner make a decision about whether to continue a treatment. We can make a diagnosis and know we’re having a real effect.”

“I like that I can do everything with clinical pathology at Cornell,” says Stokol. “Service helps patients in real-time, research expands our knowledge, teaching ensures the future. It’s the best of all worlds.”

 

 

Healthy herds

Cattle health program helps herds and humans

Herds of grazing cattle set the classic backdrop of any drive through the Empire State. New York means cows, and not just because of the scenery. Dairy farms feed millions, providing the number one agricultural industry in the state, which ranks third in the US for milk production. The economy, natural resources, and public health of the state depend on healthy cattle. For that reason, New York State has developed a program to ensure the health, productivity, and stewardship of cattle and the farms they inhabit.

The New York State Cattle Health Assurance Program (NYSCHAP) provides a free service to any interested dairy or beef farm in the region. Funded through the state’s Department of Agriculture and Markets, the program offers collaborative consultations with state or certified veterinarians specially trained to work with farmers and their herd veterinarians to increase herd health, productivity, and profitability.

NYSCHAP works to assure food safety, public health, and consumer confidence in beef and dairy products that are sold in markets across the state and deck countless family tables. The program also supports the region’s natural resources by promoting environmental stewardship and best practices for waste management.

“Many issues face modern dairy and beef farmers, from maintaining a herd and managing disease to ensuring profitability and product quality,” says Kathy Finnerty, who directs the program from her office in the AHDC. “When a farm enrolls in NYSCHAP, we form a team of advisors to develop a plan for the herd based on the goals and resources of the farm.”

A NYSCHAP farm team consists of a state field veterinarian or certified NYSCHAP veterinarian, the farm’s owner, the herd’s veterinarian, key farm employees, and other consultants used on the farm.  After reviewing basic information and conducting a walk-through risk-assessment, the team forms a herd plan, including a prioritized list of best management practices specifically tailored to the farm.

“Goals may include anything from increasing milk production and quality, to expanding the herd, to controlling disease,” Finnerty explains. “The farm’s staff and herd veterinarian work together over the year to meet the agreed-upon goals, using the herd plan as a guide. Collaboration is key, and every member’s input counts in forming and implementing the plan.”

“It’s free, voluntary, and confidential,” Finnerty adds. “The state pays for visits from both a state field veterinarian and the farm’s own herd veterinarian. The veterinary visits, the team consultations, and the herd plan they produce can all have a great impact on the health and success of a farm. That translates to the health of consumers and the success of the state itself.”

Extension veterinarians from the College’s Diagnostic Lab helped get the program off the ground in 1998. Today faculty from the AHDC continue to assist in the program’s development and implementation, train veterinarians on pertinent topics, and meet herd veterinarians to discuss the use of new testing capabilities as these new tests become available. Participating farms receive significant discounts on certain tests at the AHDC, including Johne’s disease testing and bulk tank culture testing for contagious mastitis, an infection of the udder.

All farms enroll in the core module, which addresses biosecurity, food quality assurance, environmental stewardship, management of manure, feed, water, and facilities, and the possible introduction and spread of disease. Farms may also enroll in individual modules tailored to specific diseases, including Johne’s disease, bovine viral diarrhea (BVD), salmonella, bovine leukosis, mastisis and milk quality, and environmental pathogens. Other modules specifically address beef quality, herd expansion, and cattle welfare certification.

Currently 870 farms throughout New York State participate, including 60-70 beef farms, and 35% of all dairy cattle farms in the state. Farmers interested in enrolling in NYSCHAP can contact their herd veterinarians, or go online for more information at http://nyschap.vet.cornell.edu/.

NYSCHAP utilizes 11 NYS Department of Agriculture and Markets field veterinarians, and offers a training program for private practitioners. Veterinarians interested in becoming certified complete a training class or submit a certification test. Contact Kathy Finnerty, NYSCHAP Coordinator, at kdf2@cornell.edu for more information.