News

Computer-generated model of how the human immune
system responds to the influenza virus.

The University of Rochester Medical Center has been awarded $4.7 million from the Federal government, with several options for additional funding, to establish a center to study the germs that cause lung disease.

The agreement with the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, took effect earlier this month. The agreement, renewable on a year-by-year basis, could last potentially for seven years. If the agreement lasts the full seven years, contract funding may be at least $35 million, and support could reach as much as $50 million, if NIAID exercises all its options.

Creation of the new center was led by microbiologist David Topham, Ph.D., an influenza researcher who also directs the Health Sciences Center for Computational Innovation.

While most people think of dogs, raccoons or skunks as potential rabies carriers, bats are a major source of the disease in the United States, experts say. And on Thursday, the Centers for Disease Control and Prevention announced that a Mexican teenager had become the first person on U.S. soil to die from rabies after getting bit by a vampire bat.

Experts say that as soon as exposure to a rabid animal is suspected, it's important to consult a doctor and receive a post-exposure prophylaxis vaccine. The vaccine will prevent them from getting rabies, which is almost always fatal. Because the rabies virus takes weeks to incubate, there is time for the vaccine to prevent disease even when given after exposure to the virus, said Dr. David Topham, associate professor of microbiology and immunology at University of Rochester Medical Center. The man's death could have been easily prevented if he'd sought treatment in time.

David Topham, Ph.D. stands next to an IBM supercomputer.

Since 2005, UR has experienced a 31 percent increase in research funds, culminating in the $461 million received for the fiscal year that ended last June, while the number of UR employees rose by almost 20 percent to just under 20,000. But the spillover of research to startups has been less pronounced. UR is now licensing the know-how from its research to 31 local companies that, as of about a year ago, employed 346 workers.

Both UR and RIT are trying to increase their economic presence locally. UR is teaming up with IBM to establish a $100 million high-powered computer center that will provide unique research capabilities in health-related sciences, while RIT is establishing itself as a leader in promoting cost savings in green technology and industrial sustainability.

In his office at UR's School of Medicine and Dentistry, David Topham, Ph.D. who is vice provost and executive director of Health Sciences Center for Computational Innovation, can pull up on his computer screen an image of two proteins interacting with a virus. You need the supercomputer to handle the amounts of data required for this sort of simulation, said Topham, explaining how this high-powered computer is helping researchers trying to design a vaccine against a range of viruses.

Golisano Children's Hospital at the University of Rochester Medical Center (URMC) has been awarded a five-year grant for nearly $2 million by the National Institutes of Health, as part of the Child Health Research Centers program. The program, aimed at establishing and growing centers of excellence in pediatric research, will fund basic science training for junior faculty members in pediatric subspecialty areas.

One scholar in particular that will enroll in the program during its first year is Kristin M. Scheible, M.D., Senior Instructor in Neonatology and Pediatrics and current member of Dr. David Topham's lab. The enrolled junior investigators will spend 75 percent of their time conducting research in their specialty areas. The program will help them cultivate research within their area of expertise, develop analytical and practical skills to understand and treat developmental diseases in children and establish themselves as ethically and scientifically sound clinical researchers.

Flu viruses are a great threat, whether they stem from Mother Nature or are modified by human hands to create a deadly bioweapon. The University of Rochester Medical Center will tackle both scenarios head on with a five-year contract, totaling approximately $11.9 million, from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH). The contract will further research into how we can use computer modeling to find ways of boosting human immune responses against and identify new areas of investigation into treatments for a variety of potentially lethal viruses.

Rochester has a long-standing clinical infrastructure and an outstanding track record in vaccine research. Now, we are building on this expertise, taking vaccine research into the twenty-first century by applying mathematical and computational approaches, said David Topham, Ph.D., co-director of the New York Influenza Center of Excellence (NYICE) and an expert on how the body fights the flu. There is also tremendous collaboration and cross pollination among researchers and between programs – another reason why we are able to conduct complicated clinical studies that many other universities would have a hard time doing.

Nearly 200 researchers from around the world have convened in Rochester this week to discuss new insights into flu. The meeting is the fourth annual for the National Institutes of Health's Centers of Excellence for Influenza Research and Surveillance (CEIRS) consortium. This is the first meeting to be hosted by URMC, whose New York Influenza Center of Excellence (NYICE) was established in 2007 thanks to a seven-year, $26 million NIH contract.

The NIH has charged its CEIRS centers with the twin goals of helping make seasonal influenza and future influenza pandemics less deadly, said John Treanor, M.D., chief of URMC's Infectious Disease Division. Treanor co-directs URMC's center together with David Topham, Ph.D., an associate professor of Microbiology and Immunology. People think we know more about the flu than we actually do, said Topham. It's amazing how little we actually understand. Meetings like this are a critical venue for exchanging insights that grow our body of knowledge.

A half million dollars in federal stimulus funds bought high-tech filtration and decontamination equipment to safely conduct bird flu virus experiments involving mice at University of Rochester Medical Center.

This will enhance the university's ability to remain competitive in attracting research funding and conducting important health-related research, said David Topham, Ph.D., a URMC researcher and co-director of the New York Influenza Center of Excellence (NYICE) at URMC. The equipment allows testing the effectiveness of bird flu vaccines, including testing vaccinated mice.

Scientists have uncovered the flu's secret formula for effectively evolving within and between host species: balance. The key lies with the flu's unique replication process, which has evolved to produce enough mutations for the virus to spread and adapt to its host environment.

These new findings give us insights into how we may be able to control viral evolution, said Baek Kim, Ph.D., professor in the department of Microbiology and Immunology at the University of Rochester Medical Center and lead study author.

The perception has always been that the flu virus mutates a lot, and in order to do that it has to have an enzyme that makes a lot of mistakes, but Kim's work shows that is not the case at all, said David Topham, Ph.D., associate professor of Microbiology and Immunology at Rochester and an expert on how the body fights the flu.

A new Japanese study outlines the molecular and cellular reasons why some flu vaccines work better than others and could point the way to better protection with fewer side effects.

Split-virus flu vaccines are used in the United States. The study found that whole-virus vaccines provoke a greater immune response, which has both a good and a bad side, said David Topham, Ph.D., a flu virus expert who is an associate professor of Microbiology and Immunology at the University of Rochester in New York.

The whole-virus vaccine is reactogenic, meaning that it can cause pain at the site of injection and other side effects, Topham said. The slightly lower immune response produced by a split-virus vaccine is offset by a reduction in side effects, he explained.

H1N1 vaccine

After nearly a year of headlines, worry and confusion, the H1N1 swine flu virus is now out of the news. Is it out of circulation as well? The latest data from the U.S. Centers for Disease Control and Prevention finds no states reporting widespread influenza activity and only five reporting regional activity.

It certainly seems to have died down in this country. It's gone very quiet, confirmed David Topham, co-director of the New York Influenza Center of Excellence and associate professor of Microbiology and Immunology at the University of Rochester Medical Center. Topham went on to say, I'm pretty confident that this virus is here to stay with us. It will become one of the seasonal influenzas we'll have to contend with, he said.

Microbiologist David Topham, Ph.D. discussed his work on flu and the current pandemic at 4 p.m. on Friday, Nov. 13, in the Class of '62 Auditorium (Room G-9425) at the Medical Center. The talk, part of the Second Friday Science Social lecture series, is geared mainly to faculty, staff and students at the University, though the general public is welcome as well.

Topham is an expert on how the body fights the flu, and he helps to direct a research center that is part of a key Federal network designed to fight the flu. He's busy directing studies aimed at understanding the current pandemic and preventing future ones, as well as studying infected people to learn how the body fights the flu.

With flu vaccination season in full swing, research from the University of Rochester Medical Center cautions that use of many common pain killers - Advil, Tylenol, aspirin - at the time of injection may blunt the effect of the shot and have a negative effect on the immune system.

Richard P. Phipps, Ph.D., professor of Environmental Medicine, Microbiology and Immunology, and of Pediatrics, has been studying this issue for years and recently presented his latest findings at the Bioactive Lipids in Cancer, Inflammation and Related Diseases Conference.

URMC co-investigators on the study in Cellular Immunology include: David Topham, Ph.D., an expert in the immune response to influenza and a principal investigator in the David H. Smith Center for Vaccine Biology and Immunology, and Simona Bancos and Matthew P. Bernard, of the Department of Environmental Medicine's Lung Biology and Disease Program.

The discovery of three cases of the pandemic H1N1 influenza that are resistant to a key antiviral drug is not surprising, experts say. What is worrying some is that one of the cases of resistance to oseltamivir (Tamiflu) occurred in a woman in Hong Kong who had not been treated with the drug.

But until these cases emerged, there had been no sign of oseltamivir resistance in the pandemic H1N1 flu. Keiji Fukuda, M.D., of the World Health Organization, said there is still no evidence that a resistant strain is being transmitted. That said, the emergence of drug-resistant viruses is not unexpected, according to David Topham, Ph.D., of the University of Rochester in Rochester, N.Y., especially in light of the increased use of influenza antivirals in the context of this recent pandemic.

Researchers have successfully tested for the first time a computer simulation of major portions of the body's immune reaction to influenza type A, with implications for treatment design and preparation ahead of future pandemics, according to work accepted for publication, and posted online, by the Journal of Virology. The new "global" flu model is built out of preexisting, smaller-scale models that capture in mathematical equations millions of simulated interactions between virtual immune cells and viruses.

A team of immunologists, mathematical modelers, statisticians and software developers created the new model over three years within the Center for Biodefense Immune Modeling at the University of Rochester Medical Center. The project was led by Hulin Wu, Ph.D., principal investigator of the project, director of the Center for Biodefense Immune Modeling (CBIM) and division chief of the Department of Biostatistics and Computational Biology, and by Martin S. Zand, M.D., Ph.D., co-director of the CBIM. The work was funded by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the U.S. Department of Energy.

"High-speed, accurate computer simulation tools are urgently needed to dissect the relative importance of each attribute of viral strains in their ability to cause disease, and the contribution of each part of the immune system in a successful counterattack," said Zand. "Real world experiments simply cannot be executed fast enough to investigate so many complex surprises, and we must keep pace with viral evolution to reduce loss of life."

Stained transmission electron micro-graph (TEM) of the A/CA/4/09 swine flu virus. (Photo Credit: CDC / C. S. Goldsmith and A. Balish)

As the death toll from swine flu in Mexico rises and new cases appear in the United States and elsewhere, it's easy to get caught up in a sense of mounting dread. But experts in influenza and infectious disease say the exact level of danger from the virus is still far from certain. This is something of concern [but] I think we should hold back on calling it a real threat, said David Topham, co-director of the New York Influenza Center of Excellence, part of the University of Rochester Medical Center. We always have to take these things seriously, but we have a very good system in place to respond.

In February, a group of experimental ferrets at a research facility in the Czech Republic fell ill. The ferrets had recently been injected with a culture containing what was believed to be a straight shot of the seasonal influenza virus, but their symptoms were severe and wholly unexpected. Researchers later determined that they were suffering from avian influenza; the seasonal flu culture had been contaminated with the deadly virus H5N1.

I think it points to major problems, says David Topham, Ph.D., a microbiologist at the University of Rochester Medical Center and co-director of the New York Influenza Center of Excellence. Although contamination can happen easily, he says, there should be sufficient safety measures in place to prevent it.

Last week, NIH announced that it would fund six Centers nationally to study the flu. Under the leadership of Drs. John Treanor and David Topham, and with the expertise of a large number of faculty co-investigators, Rochester will be one of these Centers. Over the next seven years, we will receive $26 million to conduct studies that will improve our understanding of the biology of the virus and of our immune response to influenza viruses and vaccines.

GlaxoSmithKline's bird flu vaccine contains a new type of adjuvant, or compound, that boosts the body's immune response. The U.S. Food and Drug Administration has hesitated to approve adjuvants, said David Topham, a microbiology professor at the University of Rochester, as they can cause side effects such as swelling and tenderness. You don’t want to put anything in a healthy person that can cause a problem, Topham said.

What stops the bird flu? Viruses infect cells by latching on to receptor molecules on the cell surface. Flu viruses bind to sialic acid (SA) receptors. Most H5N1 viruses - there are now many strains - need a receptor in the alpha2,3Gal configuration. In humans, only deep lung cells carry that SA configuration. Nose, throat, and sinus cells have SA in the alpha2,6Gal configuration.

If that doesn't sound very different, it isn't. It would only take a few small mutations for the bird flu virus to be able to latch on to human cells.

Flu expert David Topham, Ph.D., of the University of Rochester, N.Y., says this part of the flu virus mutates rapidly. It is relatively easy for the bird flu virus to accommodate such a thing, Topham tells WebMD. And when people get the infection deep in the lung, there would be selective pressure on the virus to acquire this mutation. So this adaptation to humans might not have to happen in another species. It might occur in humans.

Noelle Polakos, a 5^th year graduate student in Dr. David Topham's lab received a travel and conference award from GWIS. She attended and presented a poster at the Keystone Meeting on Viral Immunity and Advances in Influenza Research in Steamboat Springs, Colorado.

Researchers at the University of Rochester have identified a protein in the immune system that appears to play a crucial role in protecting against deadly forms of influenza, and may be particularly important in protecting against emerging flu viruses like the avian flu. The researchers believe that a vaccine made with a live but weakened strain of flu virus - such as the inhaled flu vaccine introduced last year - may activate this part of the immune system and offer the best defense against avian flu.

The findings demonstrate that when confronted by a potentially deadly flu strain, an effective first strike by T cells in the lungs can mean the difference between life and death. To immunologist David Topham, Ph.D., assistant professor of Microbiology and Immunology at the University of Rochester and lead author of the study, the findings reveal something else: a shortcoming in the world's most widely administered flu vaccines.

Rochester doctors and nurses have been chosen to lead the largest study of smallpox vaccine to date, a nationwide study of approximately 900 patients that will be conducted at seven sites around the country, including Rochester. Approximately 200 people in the Rochester area who were vaccinated against the disease as children will receive a booster shot as part of the study. John Treanor, M.D., associate professor of medicine and director of the medical center's Vaccine and Treatment Evaluation Unit, will lead the national study, coordinating doctors at all seven sites and guiding the effort to evaluate the results.

Besides Treanor, scientists involved in this study are immunologists David Topham, Ph.D., and Tim Mosmann, Ph.D., of the David H. Smith Center for Vaccine Biology and Immunology; and molecular biologist Mark Sullivan, Ph.D., of the Center for Human Genetics and Molecular Pediatric Disease.