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.
Earlier this month, the University of Rochester Medical Center again became one of only nine institutions nationwide to receive a new wave of National Institutes of Health dollars designed to pave inroads into unraveling – and treating – autoimmune diseases.
In 2003, a similar endeavor to establish nine Autoimmunity Centers of Excellence
(or ACEs) – which would supercharge research into conditions like lupus, diabetes (type 1), multiple sclerosis and some types of arthritis – also targeted URMC. Together with Duke University and the University of California, San Francisco, Rochester's is among only three of the original ACEs to be refunded, receiving at least $5 million over the next five years, and possibly more if supplementary money is awarded for additional trials.
Historically, URMC has been a powerful player in the field of immunology, with researchers knee-deep in deciphering the inner workings of the immune system, and in hot pursuit of new ways to manufacture vaccines. But according to Ignacio Sanz, M.D., chief of the division of Allergy/Immunology & Rheumatology at URMC, and also principal investigator for URMC's ACE, it's also possible the broad-reaching nature of the proposed projects was a key factor in the Rochester center's renewal.
Our studies will focus on fundamental questions – namely, how immune cells, like B and T cells, are mis-regulated, confusing the body into attacking its own tissues,
Sanz said. What we learn is likely to illuminate research across the whole spectrum of similar diseases.
Current strategies for designing vaccines against HIV and cancers, for instance, may enable some components in multi-component vaccines to cancel the effect of others on the immune system, eliminating their ability to provide protection, according to an article to be published shortly in the Proceedings of the National Academy of Sciences (PNAS). The authors also successfully tested techniques that offer a solution to newly revealed mechanisms that enable some vaccine components to outcompete others.
Andrea Sant, Ph.D., professor within the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, published a July 2005 article in the journal Immunity which revealed the quality that confers immunodominance on a peptide to be the strength and lifespan (kinetic stability) of its bond to the MHC class II protein. Kinetic stability determines whether, in the face of competing reactions, a peptide:MHC class II complex can accumulate at the surface of the dendritic cell, and then remain intact long enough to sustain T cell expansion. Dr. Sant's team found that immunodominant peptides held onto to MHC molecules ten to one hundred times longer than nondominant, or cryptic,
peptides because they fit together better. In the years since, Sant and colleagues have determined how the kinetic stability of the MHC:peptide bond has its effect.
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.
Bolstered by a five-year, $1.9 million research grant from the National Institutes of Health, Jennifer Anolik, M.D., Ph.D., assistant professor of Medicine and of Pathology and Laboratory Medicine, plans to probe why certain targeted therapies prove effective for some lupus patients, but not others.
Working with Anolik on the study are Jane Liesveld, M.D., professor of Medicine and professor at the James P. Wilmot Cancer Center; Deborah Fowell, Ph.D., associate professor of Microbiology and Immunology; and Frances Lund, Ph.D., professor of Medicine in the Division of Allergy/Immunology and Rheumatology.
