Honors & News
December 30, 2010
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.
November 10, 2010
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.
August 1, 2010
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.
June 21, 2010
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.
June 12, 2010
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.
March 31, 2010
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.
February 5, 2010
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.
November 14, 2009
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 Sociallecture 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.
November 3, 2009
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.
July 7, 2009
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.
May 18, 2009
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
globalflu 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.
May 11, 2009
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.
May 7, 2009
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.
April 28, 2009
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.
April 1, 2009
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.
February 6, 2009
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.
January 14, 2008
Researchers have found a way to selectively block the ability of white blood cells to
crawltoward the sites of injury and infection when such mobility drives disease, according to a study published today in The Journal of Experimental Medicine. The results suggest a new treatment approach for autoimmune diseases like rheumatoid arthritis, lupus and multiple sclerosis, and for conditions made worse by misplaced inflammation, like atherosclerosis, stroke and transplant rejection, researchers said.
There are many cases where it would be incredibly useful to precisely block integrin activation, and thus T cell migration,said Minsoo Kim, Ph.D., assistant professor of Microbiology and Immunology within the David H. Smith Center for Vaccine Biology and Immunology at the Medical Center, and lead author of the article.
Good examples include when our immune system attacks our own cells, or rejects a lifesaving transplant or clogs our blood vessels by mistake. The problem is that past, system-wide attempts that block all integrin activation, like the multiple sclerosis drug Tysabri, shut down not only unwanted inflammation in one locale, but also vital immune defenses elsewhere, leaving patients vulnerable to infection.
October 19, 2007
A researcher at the University of Rochester Medical Center has won the 2008 Paul Ehrlich and Ludwig Darmstaedter Prize for his contribution to the field of immunology.
The prize, which includes with a cash award of 100,000 euros, has been awarded to Tim Mosmann, Ph.D., director of the David H. Smith Center for Vaccine Biology and Immunology at the Medical Center. The Scientific Council of the Paul Ehrlich Foundation, a German organization gives the award each year to recognize achievement in Ehrlich's fields: immunology, oncology, haematology and microbiology.
May 23, 2007
Mantle cell lymphoma as seen under a microscope.
A James P. Wilmot Cancer Center scientist recently received two research grants, totaling more than $1.5 million, for separate, divergent studies of new therapies for follicular and mantle cell lymphomas.
In the first Lymphoma Research Foundation-funded project, Steven Bernstein, M.D., co-director of Wilmot's Lymphoma Biology Program at the University of Rochester Medical Center, will investigate whether rituximab, an antibody treatment for follicular lymphoma, causes the body's immune response to fight the disease. Rituximab, also known as Rituxan, is effective in treating the disease, but how it actually works remains unclear to scientists and oncologists.
Bernstein's team, which includes immunologists Shannon Hilchey, Ph.D., Tim Mosmann, Ph.D., and Alexandra Livingstone, Ph.D., will examine whether rituximab therapy generates an immune response specifically targeting the lymphoma cells.
April 11, 2007
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.
December 14, 2006
Based on experiments with worms similar to those that infest millions of children in the tropics, researchers see potential for a new way to treat asthma. Parasitic infections and asthma may cause the human immune system to react in some of the same ways, and may one day be cured by manipulating some of the same proteins, according to research published today in the journal Science.
To be effective, the immune system must
decidewhich cells and chemicals need to be ramped up to best destroy the invader at hand, be it bacterium, virus or worm. In 1986, Tim Mosmann, Ph.D., now director of the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, led a team that first described a new concept for how the immune system might make such choices: the Th1/Th2 Model.
August 21, 2006
Three researchers at the University of Rochester Medical Center have been chosen to receive research awards from Johnson & Johnson based on the potential of their work to lead to medical breakthroughs. The awards, announced today, represent the second round from the
Discovery Concept Fund,an academic-industry partnership launched in 2005. The fund is designed to nurture early-stage research by scientists who have promising ideas, but not ready access to research funding for a given project. Combined with the first round of awards given out in January 2006, the new funding brings J&J's total investment in Medical Center research this year to $400,000.
The second round award-winners were Deborah Fowell, Ph.D., assistant professor of Microbiology & Immunology; Ian Nicholas Crispe, Ph.D., associate director of the David H. Smith Center for Vaccine Biology and Immunology; and Andrei Yakovlev, Ph.D., chair of the Department of Biostatistics and Computational Biology.
With support from the award, Fowell is researching new ways to harness the body's natural regulatory lymphocytes to hold the immune system in check. Her work with regulatory T cells could lead to new drugs that either damp down the immune system when it mistakes our own cells for foreign invaders (e.g. autoimmune diseases) or pump up the immune system's attack on disease-related molecules that have fooled our system into passing them by (e.g. tumors and chronic infection).
August 4, 2006
Immunologist Tim Mosmann, Ph.D., will discuss the immune system – the assortment of defenses that keep our bodies from being overrun by an ever-adapting array of microbes, viruses, parasites, and other threats – as part of a lecture series highlighting biological and biomedical research at the University of Rochester.
Mosmann will discuss his work on the immune system at 4 p.m. Friday, Aug. 11, in the Case Methods Room (Room 1-9576) at the Medical Center. It's the latest installment of the
Second Friday Science Sociallecture series geared mainly to faculty, staff and students at the University, though the general public is welcome as well. The lectures are free. More information.
July 26, 2006
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.
June 12, 2006
A new research center whose scientists are working on better ways to treat multiple sclerosis has been established in Rochester by the National Multiple Sclerosis Society.
The University of Rochester Medical Center is bringing together experts who normally focus on Alzheimer's disease, HIV vaccines, and spinal cord repair, as well as multiple sclerosis, in a unique center designed to stimulate MS research by drawing on the expertise of scientists from a wide array of disciplines. The new Collaborative Multiple Sclerosis Research Center Award – the only one in the nation established by the society this year – is headed by neurologist Benjamin Segal, M.D., associate professor of Neurology and director of Neuroimmunology Research. Segal has enlisted several of his colleagues to direct their attention on new ways to investigate the disease.
Also taking part in the project are neurologists Steven Schwid, M.D., and Andrew Goodman, M.D., who have extensive experience with clinical trials in MS; and Howard Federoff, M.D., Ph.D., and Tim Mosmann, Ph.D., who head research centers in aging and in vaccine biology, respectively.
March 22, 2006
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.
March 1, 2006
Noelle Polakos Receives GWIS Travel and Conference Award
July 26, 2005
Scientists have taken a major step toward the goal of altering viruses, bacteria and tumor cells so that they demand attention from immune cells designed to destroy them. According to research published today in the journal Immunity, researchers at the University of Rochester Medical Center have determined for the first time a single biochemical feature of disease-causing molecules (pathogens) that, if changed, would force them to provoke an attack by the human immune system.
Recognizing molecules as "self," versus foreign invaders to be destroyed, is a central responsibility of the immune system. Tumors closely resemble self or "host" tissues and can confuse the system. Viruses and bacteria are immediately recognizable as foreign, but have learned to change shape so often that the system loses track of them. Pathogens use the same tricks to escape the immunity provided by vaccines.
In an effort to deny diseases the ability to hide, researchers have for years been asking a key question: Why do our bodies select certain, small pieces (epitopes) of each disease-causing molecule to trigger an immune response, while ignoring the rest? Those few, triggering protein fragments are termed "immunodominant." Unfortunately, the immune system sometimes makes poor choices about which epitopes to pay attention to, and which to ignore. Understanding of how immunodominance is conferred would enable vaccine designers to shift the immune system spotlight to parts of pathogens that they cannot change in efforts to escape detection. For example, a vaccine could be designed to target a protein fragment central to a virus's ability to reproduce, or to invade its prey.
"Our study identified for the first time the chemical mechanism that determines immunodominance, and proved that it can be fine-tuned," said Andrea Sant, Ph.D., a professor within the David H. Smith Center for Vaccine Biology and Immunology at the University of Rochester Medical Center, and the study's lead author. "If confirmed, the findings could launch a new wing of research seeking to re-engineer viruses, bacteria and tumor cells to make them hundreds of times more likely to be noticed and destroyed by our immune system."
February 24, 2005
A vaccine to prevent a type of cancer that kills more than 250,000 women around the globe every year is expected to become available within a year or two, thanks in large part to technology developed by scientists at the University of Rochester Medical Center.
Vaccines that prevent cervical cancer are in the final stages of testing in studies by two companies, Merck and Co. and GlaxoSmithKline (GSK). Earlier this month the two pharmaceutical giants agreed on a settlement involving patents and royalties related to the vaccines, clearing the way for continued development of their products.
The vaccine targets a group of viruses known as human papillomaviruses (HPV), which cause 12,000 cases of cervical cancer in women in the United States annually. About 4,500 women in the nation die of the disease every year. The toll is much worse in other parts of the world, where Pap smears to detect the disease in its earliest stages are not widely available. In some parts of the world, cervical cancer is the leading cause of death by cancer in women.
Research done more than a decade ago by a trio of University virologists – Richard Reichman, M.D., William Bonnez, M.D., and Robert Rose, Ph.D. – is integral to the technology, which takes aim at a portion of a class of viruses that also cause all warts. A patent application was filed, and the rights to the technology were licensed to the biotechnology company MedImmune, which then sold the license to SmithKline (which later became GSK). Now, the research is poised to save lives and become part of one of the first vaccines to prevent a form of cancer. (The hepatitis B vaccine can also prevent liver cancer.)
"The public health impact of this work – which has the potential to prevent a condition that causes significant morbidity and mortality in women – is enormous, both nationally and internationally," says David Guzick, M.D., Ph.D., dean of the School of Medicine and Dentistry and professor of Obstetrics and Gynecology.
February 20, 2004
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.
November 5, 2002
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.
- Department of Microbiology and Immunology
- New York Influenza Center of Excellence
- Human Immunology Center
- Division of Infectious Diseases
- Division of Allergy, Rheumatology and Immunology
- Department of Biomedical Engineering
- Cancer Center
- Tissue Specific T Cell Function Research Group
- New Vaccine Surveillance Network
- Clinical Trials Database
- HIV Vaccine Trials Unit