Researchers have found a way to selectively block the ability of white blood cells to crawl
toward 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.
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.
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.
Flu GrantApproved by NIH
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.
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 decide
which 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.
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).
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 Social
lecture 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.
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.
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.
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 5th 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.
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."
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.
Instant StrikeAgainst Deadly Flu Viruses
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.
