Category Archives: Published

Researchers discover what cancer cells need to travel

Feb. 21, 2012

Cancer cells must prepare for travel before invading new tissues, but new Cornell research has found a possible way to stop these cells from ever hitting the road.

Researchers have identified two key proteins that are needed to get cells moving and have uncovered a new pathway that treatments could block to immobilize mutant cells and keep cancer from spreading, says Richard Cerione, Goldwin Smith Professor of Pharmacology and Chemical Biology at Cornell’s College of Veterinary Medicine.

The study, co-authored by graduate student Lindsey Boroughs, Jared L. Johnson, Ph.D. ‘11, and Marc Antonyak, senior research associate, is published in the Journal of Biological Chemistry (286:37094-37107)

Most adult cells stay stationary, but the ability for some to move helps embryos develop, wounds heal and immune responses mobilize. When migrating cells go astray they can cause developmental disorders, ranging from cardiovascular disease to mental retardation. Metastasis (the spread of cancer from one part of the body to another) also relies on cell migration. How exactly cancer cells migrate
and invade tissues continues to be a mystery. However, Cerione’s lab uncovered a potentially important clue when it noticed that cancer cells gearing up to move would collect a protein called tissue transglutaminase (tTG) into clusters near the cell membrane.

meta“TTG is turning up in many aspects of human cancer research and seems to be contributing to the process that turns cells cancerous,” said Cerione. “Lindsey and Marc discovered that cells must gather tTG into a specific place in their membrane before they can move. But tTG is usually inactive, and we’ve been trying to understand how a cell gets this protein to the exact right place so that it can be activated to stimulate cell migration.”

Observing breast-cancer cells in culture, Cerione’s lab found a missing link in our understanding of cell migration: Cancerous cells become hyperactive invasion vehicles by using tTG together with other proteins like wheels, poking them through the surface to form a “leading edge” that pulls the cell forward. But to get the wheels to the leading edge, it turns out they need another protein to roll them there – a “chaperone” protein called heat-shock-protein-70 (Hsp70).

“We’ve known for years that Hsp70 acts as a chaperone to other proteins, ensuring that they assume the right structure and behave properly when a cell is under stress,” said Cerione. “Heat shock proteins have also been implicated in cancer, although scientists have been trying to understand their exact role in cancer. Our research has uncovered a previously unknown role for these chaperones – helping tTG get to the leading edge. TTG must be in this location for cancer to spread.”

migrating cervical cancer cell

A migrating cervical cancer cell stained for tissue transglutaminase (green). Cells must gather this protein at their leading edge in order to move.

When cells become stressed, Hsp70 influences the behavior of their “client” proteins, ensuring they keep the right shape. Cells need chaperones like Hsp70 to ensure that various proteins work correctly and don’t warp, but these same chaperones can help cancer cells spread by helping move tTG to the membrane surface. Using inhibitors that block the function of chaperones, Cerione and his team paralyzed Hsp70s and stopped breast cancer cells in culture from gathering tTG into a leading edge, effectively immobilizing them.

Exactly how Hsp70 gets tTG going remains unknown, but Cerione believes other proteins are involved.

“If we can better understand how Hsp70 influences tTG, we can figure out ways to modulate that interaction to immobilize cancer cells and keep them from becoming invasive,” said Cerione. “We suspect Hsp70 is using a third kind of protein to move tTG, and that’s what we’re trying to figure out now. Finding the next link in this chain of events could have important consequences for preventing cancer migration and metastasis.”

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

—–

Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/Migration.cfm

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Feb12/CancerMovers.html

Ithaca Journal

http://www.theithacajournal.com/article/20120222/LIFE/202220336/Cornell-scientists-find-cancer-cells-need-travel?odyssey=mod|newswell|text|Life|s

PhysOrg

http://www.physorg.com/news/2012-02-cancer-cells.html

ECNMag

http://www.ecnmag.com/News/Feeds/2012/02/blogs-the-cutting-edge-researchers-discover-what-cancer-cells-need-to-tra/

Zeit News

http://www.zeitnews.org/biotechnology/researchers-discover-what-cancer-cells-need-to-travel.html

My Science

http://www.myscience.cc/news/2012/what_cancer_cells_need_to_travel-2012-cornell

Reddit

http://www.reddit.com/r/science/comments/q0swt/cancer_cells_must_prepare_for_travel_before/

Laboratory Equipment

http://www.laboratoryequipment.com/news-Proteins-Key-to-Stopping-Cancer-from-Spreading-022312.aspx

Conservation in action

First Indonesian to receive major fellowship will help save world’s rarest rhinoceroses

Deep in the Indonesian rainforest on the island of Java roam the last of earth’s most critically endangered large mammal species: the Javan rhinoceros. Once Asia’s most widespread rhinoceroses, these secretive forest-dwellers disappeared altogether from the continent’s mainland in October 2011, when the last individual was found dead in Vietnam with its horn chopped off by poachers. A single population of just 40 rhinoceroses survives in the western half of Java’s Ujung Kulon National Park, cramped into a corner of the island that has reached its carrying capacity.

The Indonesian government recently endorsed a daring plan to expand the range of their emblem species by establishing a second population with more room to grow. Yet a major concern remains. The plan involves moving some rhinoceroses from the isolated westernmost tip of Java to the eastern side of the park—an area surrounded by 19 agricultural villages whose inhabitants rely on water buffalo to work their rice paddies. No fences limit the wanderings of these loosely managed buffalo, which regularly pass into the park and could spread diseases that would quickly decimate the rhino’s population.

Cornell postdoc Dr. Kurnia Khairani has received a Fellowship Training Grant from the Morris Animal Foundation to address this problem. With the help of faculty and students at the College of Veterinary Medicine, Khairani is combining fieldwork in Indonesia with labwork and training at Cornell to improve the health and outlook of Javan rhinoceroses. It is the first time an Indonesian has received this prestigious award, and the first time a Cornell fellow will be trained in conservation medicine.

“Of the five rhinoceros species the Javan is the rarest, and Khairani’s work is critical to its future,” said Dr. Robin Radcliffe, director of the Cornell Conservation Medicine Program, one of the world’s foremost experts working in rhino conservation. Radcliffe oversees the project and is excited by its possibilities. “Khairani herself is a major investment for conservation efforts in this region: she will take her Cornell training back to Indonesia and become a decision-maker in her own country. Cornell is involved in real-world conservation, training people who will use what they learn here to tackle new problems in the race to preserve biodiversity.”

A postdoc in the laboratory of immunologist Dr. Julia Fellipe, Khairani will work under the joint mentorship of Fellipe and Radcliffe. Additional mentorship from epidemiologist Dr. Daryl Nydam and microbiologist Dr. Pat McDonough will round out Khairani’s skills.

Conducting a preliminary health survey of village buffalo, Khairani found several diseases of concern to rhinoceroses, including blood parasites, salmonellosis, and leptospirosis. With highly infectious diseases such as SARS, West Nile Virus, and Avian Influenza making worldwide headlines for crossing species barriers and ecosystems, it is critical to get this historic move of the rarest rhinoceros right the first time. Khairani’s ongoing survey will focus on hemorrhagic septicemia, a bacterial disease linked to four recorded die-offs of Javan rhinoceroses in the region. Khairani will determine the prevalence, distribution, and risk of contracting septicemia faced by the buffalo population; conduct questionnaire-based interviews with buffalo owners to determine management factors that might contribute to the regional epidemiology of the disease; and propose possible interventions.

The project also involves outreach, educating local public health officers and villagers on septicemia diagnosis and management through hands-on training. It has also opened doors for Cornell veterinary students to gain valuable hands-on international experience, and several have already conducted internships in Indonesia with Khairani through Cornell’s Conservation Medicine Program with funding by Expanding Horizons.


“Knowledge of the region’s diseases will help veterinary officers improve the health of buffalo, a resource crucial to the region’s economic vitality,” said Khairani. “Healthier buffalo will enhance the well-being of local villagers while reducing their impact on the park. Improving our understanding of animal health in the area will help reduce the risk of disease transmission from livestock to rhinoceroses. This is essential to establishing a second habitat and population of the rare Javan rhinoceros, a crown jewel of Indonesia’s amazing biodiversity.”

‘Scopes Magazine
February 2012

Cornell’s satellite animal hospital enters second year

Cornell University Veterinary Specialists extends advanced clinical capabilities and education to NY Metro area

January 14 marked the first birthday of Cornell University Veterinary Specialists (CUVS), the College of Veterinary Medicine’s satellite referral and emergency hospital in Stamford, CT. In less than a year, CUVS has served the medical needs of more than 2,500 animals referred from over 400 veterinarians across the region for advanced diagnostics and treatment in emergency and critical care, cardiology, internal medicine, orthopedic and soft tissue surgery, and oncology.

As collaborations and caseloads continue to grow, CUVS, the nation’s largest academically affiliated veterinary center, is broadening its impact on pet-owners and the veterinary community across the Northeast with multiple educational initiatives.

“CUVS has become a leading veterinary referral center in the NY metropolitan area,” said Dean Michael Kotlikoff. “As a College we are engaging in academic referral medicine in the same way that the strongest medical colleges’ academic medical centers lead human medicine. In the absence of an academic footprint in the NY metropolitan area, we have added a previously unavailable option to access specialty services and continuing education.”

Monthly continuing education lectures for area veterinarians, held in the center’s 45-seat classroom, enable practitioners to stay up-to-date on important clinical topics while earning nationally-approved professional credits.  Regularly held education sessions for local pet owners, led by CUVS specialists, have covered topics as diverse as pet adoption, first-aid, and geriatric care. Partnering with Mercy College’s programs in veterinary technology, CUVS also offers frequent labs, lectures, and clinical externships for students and professional technicians.


In Fall 2011 CUVS held its first all-day continuing education event for referring veterinarians. More than 100 veterinarians attended the sold-out program entitled The First 24 Hours: A Multifaceted Approach to the Emergency Patient at the Hyatt Regency in Old Greenwich, CT. Faculty members from the College of Veterinary Medicine in Ithaca joined CUVS specialists to lecture on a range of topics in emergency medicine and guide labs that offered hands-on experience.

Veterinarians choosing the CPR lab practiced resuscitating a robotic virtual dog under the guidance of its creator, Dr. Daniel Fletcher, assistant professor in the section of emergency and critical care. Dr. Margaret Thompson, section chief of imaging at the Cornell University Hospital for Animals, led the computer-based laboratory in emergency radiology of the thorax and abdomen.

“Feedback from attendees was very positive, and we all enjoyed meeting local veterinarians face-to-face,” said Dr. Susan Hackner, Chief Medical Officer of CUVS, and a double-boarded specialist in Internal Medicine and Emergency & Critical Care. “The veterinary field is a small community, and we do refer cases back and forth, but we don’t often get a chance to meet as a group to get to know each other. Putting faces to names helps us forge stronger bonds with our referring veterinarians, and we look forward to holding more events like this.”

Educational opportunities at CUVS are also available to Cornell’s veterinary students, who are eligible to complete observational externship rotations at the specialty referral center, as several have already done.

Collaborations between the College and CUVS extend to faculty and clinicians.

“The College’s faculty help read our imaging studies, and College clinicians have used our services for consulting,” said Hackner. “Dr. Meg Thompson is training us to get the most out of CT scanning, and we are working with Dr. Wakshlag in Nutrition to open CUVS to nutrition resident rotations. Dr. Marta Castelhano has helped us to set up an active research site collecting samples for the College’s nationally recognized DNA Bank.  We look forward to further deepening these collaborations.”

Quick facts:

  • An advanced diagnostics and treatment center for pets with serious or emergency health issues.
  • Specialty referrals and 24/7 emergency and critical care
  • Six specialists, two part-time specialists, three emergency veterinarians
  • Specialties include emergency & critical care, orthopedic and soft-tissue surgery, internal medicine, cardiology, oncology, and a recently added ophthalmology service
  • 20,000-square-foot facilities include:
    • Intensive care unit; emergency room; three surgery suites with interventional radiology and fluoroscopy; imaging suites with CT scanner, digital radiology, echocardiography, ultrasound; 45-seat classroom auditorium; onsite apartment for visiting faculty and externs
    • Visit www.cuvs.org to learn more

‘Scopes Magazine
February 2012

Reverse genetics better vaccines

Cornell-Israel collaboration works backwards to fight virus threatening livestock trade worldwide

European livestock beware: bluetongue virus is coming your way, and it’s deadlier than ever. Once limited to warmer climes, the insect-borne virus’s new highly pathogenic strain has been spreading northward since 2006, reaching farther into Europe than ever before. Bluetongue’s rise threatens ruminants and the industries depending on them. Sheep and deer suffer most, developing dangerously high fevers, swollen mouths, and occasionally the disease’s signature blue tongue. Most infected sheep and deer die; other ruminants (cattle, goats, camels, buffalo, and antelopes) show milder symptoms but can carry the disease, further enabling its spread.

Illnesses, deaths, and international trade restrictions due to bluetongue have cost the world economy billions, including the United States, whose more benign strains still hinder livestock-related exports to bluetongue-free countries. Vaccines work weakly at best: with 25 separate strains each needing yearly updates, the quickly-evolving bluetongue virus seems to defy defense.

In the arms race between virus and victim, human knowledge is catching up. Dr. John Parker, virologist at Cornell University College of Veterinary Medicine’s Baker Institute for Animal Health, has joined Israeli microbiologist Dr. Marcelo Ehrlich of the University of Tel Aviv to learn what makes bluetongue tick, unlocking the inner workings of its deadliest strain with discoveries that could help in designing a lasting universal vaccine.

“No one thought bluetongue would spread this far, and with current vaccines even the most watchful countries can’t protect themselves from it,” said Parker. “Insects carrying bluetongue don’t respect national borders, and climate change has let them expand their range. Meanwhile this new strain is especially virulent: good at bursting through cells to infect new ones. If we can learn how bluetongue kills cells and why this strain is so good at it, we may be able to better control its spread.”

When bluetongue invades a cell it creates a protein called NS3, reproduces, and eventually bursts through the cell. All strains produce NS3, but the more virulent strains produce an altered form. When experiments in Israel suggested NS3 helps degrade cells so the virus can escape, Ehrlich contacted Parker, a former collaborator, who studies cell death.

The pair has created a novel plasmid-based system to discover exactly what NS3 does using reverse genetics. While standard “forward” genetics start with a trait then look for the genes influencing it, recently developed “reverse” genetics systems manipulate specific genes to look for their effects. Parker and Ehrlich are making mutant bluetongue viruses that alter NS3 to see what it does in a cell.

“Reverse genetics has become the gold standard for doing molecular virology,” said Parker. “It’s particularly useful for studying specific proteins. But until recently it was very difficult to develop these systems for reoviruses, the family to which bluetongue belongs.”

In 2006 one of Parker’s collaborators created a new reverse genetics system that uses plasmids, easily copied pieces of bacterial DNA, to insert viral mutants directly into cells, skipping steps that once impeded the study of reoviruses.

“The majority of Cornell’s microbiology labs do this every day: they take plasmid DNA, mutate it, and study the effect on a protein,” said Parker. “It’s much more convenient and makes transferring genetic material between labs easier, enabling better collaboration. In Israel, where virulent bluetongue is common, Marcelo will conduct experiments that for biosecurity reasons could never be conducted in the US, where strains are relatively benign.”

The researchers took an unusual route in constructing the mutant viruses they will study: hiring a company to synthesize them from scratch.

“These days you can make a pathogen by putting in an order,” said Parker. “It was first done for Polio virus, and more and more researchers are taking this approach. It’s cheaper and faster than paying grad students to spend months cloning genes. People used to learn PCR—nowadays my lab staff learn how to place an order, making sure the DNA sequence they ask for is right.”

“Viruses are often seen as mysterious and dangerous things that are hard to control. There’s some truth to that, but we are making significant progress in our abilities to manipulate viruses in ways that help us understand them better in order to develop better vaccines and treatments.”

Their work is supported by the US-Israel Binational Agricultural Research Development (BARD) Fund, which funds collaborative research to solve agricultural problems.

File:Map of molecular epidemiology of bluetongue virus in Europe.gif

The molecular epidemiology of bluetongue virus (BTV) since 1998: routes of introduction of different serotypes and individual virus strains. 

Map Source

‘Scopes Magazine
February 2012

Icelandic horses travel to Cornell

Horses will help unlock immunological mysteries of allergies and herpes

For horses, Iceland is a safe haven from disease. Several pathogens never made it to the island, whose native horses evolved for almost 1,000 years in isolation. Without facing diseases common outside, such as equine herpesvirus type 1 (EHV-1) and insect-induced allergies (called sweet itch or summer eczema), Icelandic horses never had to develop immunity to them. But immunological ignorance comes at a price: When they leave the country, these internationally popular horses are unusually vulnerable.

Yet in a discrepancy that has long puzzled immunologists, expatriate Icelandic horses give birth to far hardier foals. Born outside Iceland, these foals are up to fifteen times less likely than their parents to develop allergies. In all breeds, foal and adult immune systems work very differently. Learning how and why could help prevent allergies earlier and enable better vaccines protecting foals from early-developing diseases like EHV-1.

Dr. Bettina Wagner, equine immunologist at the College of Veterinary Medicine, works with collaborators at Cornell and in Iceland to unravel the mystery of neonatal immune development with the help of Icelandic horses.

In February 2012, 15 pregnant mares traveled from their native Iceland to Cornell University, meticulously protected from exposure to several common pathogens. With the help of collaborators at the University of Iceland at the Institute for Experimental Pathology Keldur in Reykjavik, Dr. Wagner’s group receives regular samples from the mares’ first brood born in Iceland last Summer. Comparing foals in Iceland to their forthcoming U.S.-born siblings will reveal how separate factors (environmental and maternal) affect immune development.

Clinical collaborators at Cornell assisting with the project include Drs. Gillian Perkins and Dorothy Ainsworth. Dr. Klaus Osterrieder in Berlin, Germany will help in the study of EHV-1 while Dr. Mandi deMestre of the United Kingdom will collaborate on the immune regulations analysis. Cornell professor Dr. Hollis Erb will advise on the statistical analysis of the data.

“We want to know why foals born outside Iceland have better protection than those born in Iceland,” said Dr. Wagner. “It could be due to time of exposure, environment, or some combination of these, but the evidence points more to what the mother passes on.”

Dr. Wagner thinks that protective power may lie in a mare’s milk. Some mammals, including humans, start absorbing antibodies while in the uterus, but horses receive all immunities after birth. To absorb immune protection, newborn foals must quickly drink colostrum, which is packed with immune components.

Mares encountering new allergens may become hypersensitive to the antibodies their systems produce in response. But when they pass these antibodies on through milk, Dr. Wagner thinks that the foals’ budding immune systems may learn to use those same antibodies more constructively.

Dr. Wagner’s group investigates specific antibodies called immunoglobulin-E (IgE), which can go astray in allergic diseases, reacting to harmless stimuli and causing inflammation. Building our understanding of early immune development in horses and humans could help doctors treat allergies and early-striking diseases in both species.

“If we know how allergic diseases start early in life we can interfere before they develop,” said Dr. Wagner. “Horses are a valuable model for human allergies, for which regulatory mechanisms develop very early. It’s difficult to investigate human neonatal immunity, because most maternal immune transfer happens before birth. The horse system is more controllable, especially in Icelandic horses, and can reveal the separate effects of maternal transfer and environmental exposure.”

The study may improve protection from EHV-1, which often strikes before current vaccines designed for adult immune systems can protect foals.

“If we can learn how immune responses in foals differ from those in adults, we can use specific immune reactions that foals can mount early in life to develop better neonatal vaccines for earlier protection from a wide array of infectious diseases.”

This research is funded by the Harry M. Zweig Memorial Fund for Equine Research.

‘Scopes Magazine
February 2012

Cornell China Dairy Institute teaches second crop of food-animal veterinarians from across China

For four weeks this past fall over two dozen dairy veterinarians converged on a private farm in Sanhe City, 37 miles east of Beijing. Here in China’s Heibei province, the Cornell University College of Veterinary Medicine has partnered with Huaxia Dairy as well as local Chinese educational, government, and agricultural institutions to lead an international collaboration that is benefiting animal health and food safety in China and beyond.

Cornell China Dairy Institute has provided hands-on continuing education to approximately 70 Chinese veterinarians and veterinary technicians since its launch in September 2010. During the four-week program, participants from across China attend morning lectures at Sanhe City Vocational Education College followed by afternoon hands-on training at the Huaxia Dairy farm taught by Cornell veterinarians, veterinary students, and lab technicians.

Revenue from the program goes to support the College’s local dairy programs in New York State, including food-animal externships and the highly successful Summer Dairy Institute on which the China program is based.

“This is one of the few international veterinary education programs to offer live hands-on veterinary training as well as lecture-based instruction,” said Dr. Lorin Warnick, associate dean for veterinary education at Cornell. “As agriculture and associated economies become increasingly globalized, the US has a growing interest in international disease management, food safety, and public health. The goals of the program are to advance clinical skills of veterinary staff and improve cattle care and welfare on Chinese dairy farms.  Our faculty and students benefit from seeing the dairy industry firsthand in the world’s most populous country and one in which agricultural practices are changing rapidly.”

Tailored to meet the current needs of the veterinary community in China, content integrates topics such as how to care for sick or injured cows, calf health and heifer-raising, dairy reproduction, and techniques for ensuring high quality milk production.

“The China dairy program is part of the College’s global efforts and will help to transform animal health training in this region of the world,” said Dean Michael Kotlikoff. “The global community is connected in ways that are critical to the health and well-being of animals, people, and the environment everywhere. Cornell is positioned well to help influence the direction veterinary medicine takes, in the United States and around the world.”

The timing is right for this type of initiative, according to Charles Shao, CEO of Huaxia Dairy Farm, who explained that China’s dairy industry is presently in a growth phase.

“There is an intense desire to improve efficiency and production in China and to be able to support increased consumer demand for high quality milk and dairy products,” said Shao. “This collaboration has the potential to have a strong impact on the delivery of veterinary services to dairy farms in China.”

The program also supports goals outlined in the College’s strategic plan, including finding opportunities to influence the standards for veterinary practice followed around the world and providing teaching opportunities for Cornell veterinary students who may be interested in a career in academia.

Josh Boyden ’12 spent two weeks in China as a teaching assistant in October 2011.

“While faculty lectured in the mornings, employees would present us with cases and questions on the farm that demanded immediate attention,” said Boyden, who plans to go into large-animal practice in the Northeast after graduation. “The chance to interact with enthusiastic employees and promote good on-farm practices helped reinforce the importance of basics and offered great perspective and personal satisfaction.”

This year’s teaching team also included teaching assistant Karen James ’12; PhD student Dr. Soon Hon Cheong; alum Dr. Mark Thomas ’97; and Drs. Lorin Warnick, Charles Guard, Daryl Nydam, Robert Gilbert, Rodrigo Bicalho, Gary Bennett, and Michael Zurakowski.

“As the program grows, so do the College’s opportunities for international engagement,” said Warnick. “Most participants are dairy farm staff, but we have also begun to see graduate students attending from the Chinese Agriculture University in Beijing. Feedback has been very positive about the value of the course material.”

Support for the Cornell China Dairy Institute comes from student tuition, Huaxia Dairy, Pfizer Animal Health, the U.S. Grains Council, Alta Genetics, Land O’ Lakes, Sanhe City Vocational Education College, and the Sanhe City government.

‘Scopes Magazine
February 2012

How unchecked alarms can spark autoimmune disease

November 29, 2011

A white blood cell engulfs an invading Bacillus anthracis

A neutrophil (yellow), the most abundant white blood cell type and the first line of defense against invading microbes, engulfs Bacillus anthracis (orange), the agent of anthrax. The bacteria break down, releasing DNA that triggers an immune response.

One in five Americans suffers from autoimmune disease, in which the immune system goes off-track and attacks the body’s own cells. Cornell researchers have identified a signaling mechanism in immune-system cells that may contribute to this mistake, opening the door for possible new therapies for autoimmune diseases such as lupus and arthritis.

Cynthia Leifer, assistant professor of microbiology and immunology in the College of Veterinary Medicine, and colleagues described the mechanism in the August issue of the European Journal of Immunology. The problem lies in what are called innate immune cells, the first responders to infection.

“Innate immune cells have internal watchdogs called TLR-9 receptors that set off alarms whenever they encounter invaders,” said Leifer. “They look for general classifying patterns [in DNA] to determine whether something is a virus, bacterium, protozoan, or part of self.”

However, some of these patterns exist both in invading organisms and the body’s own cells, so mistakes can arise.

Cynthia Leifer

Leifer

“We are mapping the critical regulatory mechanisms that keep these receptors from responding to self-DNA so that we can know if and how they predispose people to autoimmune disorders when they fail,” Leifer said.

Innate immune cells engulf things that look dangerous, tear them open, and release their components, including DNA. When TLR-9 receptors see DNA that identifies microbes, they send a signal to fire up more immune-system activity, including inflammation and the creation of antibodies. But before a receptor can work, enzymes in the cell must prepare it by chopping off part of the receptor molecule and leaving a part that can bind to microbe DNA.

From there, Leifer believes it’s a numbers game. If too many receptors are prepared, they may respond to the small amount of self-DNA that makes its way into immune cells, triggering an autoimmune response. So the immune cell has a regulatory mechanism, an enzyme pathway that cuts prepared receptors in a second place.

Working with cells in culture, Leifer identified this second chopping event, which cuts TLR-9 at a different site. This produces a molecule that binds to DNA, blocking it from reaching the prepared receptors, and does not send a signal.

“People without autoimmune diseases have the right balance of these two chopping events,” Leifer said. “Our studies suggest that people with a propensity for these diseases might have a defect in this pathway that allows more prepared receptors to signal for immune responses. This may be a potential target for therapies designed to help quiet those alarms.”

A second but interrelated problem Leifer has tackled involves how TLR-9 moves through an immune cell from the placewhere it is created to its working site. In earlier work she described the protein sequences in TLR-9 that act as address labels guiding where the receptor travels.

“We think they’re interrelated because if you don’t travel properly you don’t get chopped properly,” she said. “If TLR-9 ends up in the wrong place at the wrong time, it can sound a false alarm.

Leifer’s research is supported by the National Institutes of Health.

Carly Hodes ’10 is a communication specialist at the College of Veterinary Medicine.

—–

Original Press Release:

Cornell University College of Veterinary Medicine news

http://www.vet.cornell.edu/news/leifer.cfm

 

Media Hits:

Cornell Chronicle

http://www.news.cornell.edu/stories/Nov11/LeiferDNA.html

Medical Xpress (PhysOrg)

http://medicalxpress.com/news/2011-11-unchecked-alarms-autoimmune-disease.html

MyScience

http://www.myscience.us/wire/how_unchecked_alarms_can_spark_autoimmune_disease-2011-cornell

Bionity

http://www.bionity.com/en/news/135431/how-unchecked-alarms-can-spark-autoimmune-disease.html

R&D Mag

http://www.rdmag.com/News/Feeds/2011/11/general-sciences-how-unchecked-alarms-can-spark-autoimmune-disease/

ECN

http://www.ecnmag.com/News/Feeds/2011/11/blogs-the-cutting-edge-how-unchecked-alarms-can-spark-autoimmune-disease/

Futurity

http://www.futurity.org/top-stories/false-alarm-can-spark-autoimmune-disease/