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URMC Awarded Nearly $6 Million to Study Deadly Bone Infections

Monday, November 6, 2017

Bone infection, while relatively rare, can be debilitating and potentially fatal. In recent years, researchers in the Center for Musculoskeletal Research at the University of Rochester Medical Center have made several discoveries that position them to advance new treatments and possible cures for bone infections. Now, a nearly $6 million, 5 year award from the National Institute of Arthritis and Musculoskeletal and Skin Disease at the National Institutes of Health, will allow the group to create a new multidisciplinary research program devoted to studying bone infections.

The CMSR has been among the top five NIH-funded orthopaedic research centers in the nation for over ten years, and Edward Schwarz, Ph.D., Burton Professor of Orthopaedics and director of the CMSR, has been the top NIH-funded orthopaedic researcher in the nation three years running. This new grant, awarded to Schwarz and throng of researchers from across the University of Rochester and beyond, brings the center’s total forecasted earnings for 2017 to $28 million.

Of the millions of Americans who have joint replacement surgeries each year, less than five percent come away with an infection. But this minority of patients must endure a long and difficult road to recovery, if they recover at all. The vast majority of these infections are caused by a bacteria called Staphylococcus aureus, including the dreaded methicillin-resistant strain (MRSA), which causes sepsis and death in 13 percent of infected patients.

Patients who survive these infections face multiple surgeries to remove infected tissue, months of strong antibiotic treatments, and a high likelihood of re-infection. For a long time, researchers have been working to understand how this bacteria evades treatment and Schwarz believes he has figured out.

Together with Karen Bentley, director of the Electron Microscopy Core at URMC, Schwarz showed that the bacteria can crawl deep into tiny channels in bones, possibly taking shelter there and later emerging to re-establish an infection. Though S. aureus was originally thought to be incapable of movement, Bentley and Schwarz, in collaboration with James McGrath, Ph.D., professor of Biomedical Engineering at URMC, and his spin-off company, SiMPore Inc., showed that this bacteria can migrate through tiny pores in membranes in the lab.

This new grant will allow Schwarz and Hani A. Awad, Ph.D., professor of Biomedical Engineering and Orthopaedics in the CMSR, to investigate exactly how S. aureus gets into bone and develop new treatments that target those mechanisms. Microbiologists Steven Gill, Ph.D., and Paul Dunman, Ph.D., in the Department of Microbiology and Immunology, will help the team develop new antibiotics to inhibit bone infection, which will be 3D printed into spacers that replace infected joint implants. Delivering the antibiotic at the site of infection may save patients’ limbs and lives.

Schwarz has also been working to understand what makes certain patients more susceptible to S. aureus infections than others, including why some patients recover relatively easily, while others die.

“Death following surgical site infection is not random,” said Schwarz. “By studying patient immune responses to this bacteria, we might be able to predict who will be fine and who will need extra medical attention.”

S. aureus can also become resistant to antibiotics, making it extremely deadly and difficult to eradicate. Better understanding patients’ immune reactions to the bacteria may provide new approaches to defeating it.

In an international study of more than 300 patients with infected total joint replacements, Schwarz and his team including John Daiss, Ph.D., and Chao Xie, M.D., in the CMSR, found that patients fared well if their immune systems attacked a certain S. aureus protein, and poorly if they attacked another. Patients who produced antibodies attacking autolysin, a protein important for cell division, were protected. Those who produced antibodies against a family of iron sensing determinant (Isd) proteins, which help S. aureus sap nutrients from its host, were more likely to experience sepsis and even die.

It is unclear why antibodies that attack Isd proteins are bad for patients, and Schwarz is determined to use this new funding to figure it out. He will also analyze the full complement of antibodies produced by patients infected with several types of staph bacteria to see if there are more good- and bad-cop antibodies that could help inform new treatments.

The Clinical Research Core of this program will be run by Stephen L. Kates, M.D., at Virginia Commonwealth University.

Read More: URMC Awarded Nearly $6 Million to Study Deadly Bone Infections

“Bubbles” Boost Search for Treatment to Aid Head and Neck Cancer Patients

Wednesday, October 25, 2017

Overby Photo

Catherine Ovitt, Danielle Benoit, and Lisa DeLouise

A scientific team at the University of Rochester is using innovative technology to discover preventative treatments for salivary gland radiation damage typical for head and neck cancer patients—and recently received a $3.8 million National Institutes of Health grant to support their investigation.

Cancer patients can lose salivary gland function during treatment for head and neck tumors. The irreversible damage, which prevents patients from producing saliva, often results in permanent dry mouth and makes it difficult to eat, speak, and swallow. The team will develop salivary gland tissues using a unique chip technology called “microbubbles,” which are tiny spherical wells or bubbles that can hold cells.

The use of the microbubble platform is based on several years of salivary gland research, led by Catherine E. Ovitt, Ph.D., associate professor of Biomedical Genetics, a member of the UR Center for Oral Biology, and an expert in the repair and regeneration of salivary glands, and Danielle Benoit, Ph.D., associate professor of Biomedical Engineering and an expert in drug delivery systems and hydrogel platforms for tissue engineering approaches. Together with Lisa A. DeLouise, Ph.D., associate professor of Dermatology and Biomedical Engineering, who developed and received several patents for the microbubble concept, the scientists are working as co-principal investigators on the NIH project.

Their goal is to find drugs that could be given to patients prior to radiation treatment that would prevent damage to the glands.

“Dr. Ovitt and I have shown through years of investigation that being able to develop functional salivary gland tissue for testing is the key to solving this problem,” Benoit said. “So, it’s microbubbles to the rescue.”

Expanding cells and tissue outside of the body is elusive. In this case the process involves taking salivary gland cells that have been removed from humans undergoing surgery, expanding the cells, and studying their reaction to various drugs.

A major problem, however, starts to occur as soon as the tissue is removed from the body and isolated: Cells immediately begin to lose their natural function. In the body, cells send signals and secrete proteins that are essential for their survival. In a culture plate in a laboratory, however, these signals and proteins are diluted and dispersed, making the cells no longer viable.

DeLouise’s technology at first glance looks similar to a cell culture petri dish, a round piece of silicone about the size of the large cookie. But within the dish are an arrangement of thousands of tiny round “micro-wells,” each one comprising a minuscule compartment for cell growth and tissue formation. The unique shape of each microbubble creates a niche that concentrates the cells, allowing them to proliferate and form salivary gland units.

The microbubbles come in different sizes, and the beauty of the technology is that scientists can grow cells in thousands of bubbles at one time. DeLouise can make dishes the size of a dime that include more than 5,000 microbubbles. In addition, Benoit’s lab has produced hydrogel materials that can be placed inside each microbubble that further allow the cell to maintain its structure and function.

If the team can successfully grow human salivary gland cells in the microbubbles, they say, they will also be able to rapidly test thousands of existing Food and Drug Administration-approved drugs on the salivary tissue using the microbubble technology.

“Only one treatment is currently available for radioprotection but it comes with many side effects, so most patients discontinue it,” Ovitt said. “There is a great need for additional ways to either cure or prevent this debilitating condition.”

The team is collaborating with Shawn D. Newlands, M.D., Ph.D., M.B.A., chair of the Department of Otolaryngology and member of the Wilmot Cancer Institute’s head and neck oncology team, to collect salivary tissue from consenting patients undergoing salivary gland surgery. Salivary gland cells are isolated from these tissues for seeding into microbubbles for the investigation. Additionally, Paul Dunman, Ph.D., associate professor of Microbiology and Immunology, will provide high-throughput drug-screening expertise during the second phase of the project, which is contingent upon successful development of the human gland chips.

Read More: “Bubbles” Boost Search for Treatment to Aid Head and Neck Cancer Patients

Study Will Explore Link Between HIV, Micro-Strokes, and Dementia

Monday, October 2, 2017

New research will seek to understand why people who are HIV positive are more susceptible to a progressive cerebrovascular disease that can ultimately give rise to dementia. One of the goals of the research is to identify new ways to prevent the blockages that occur in blood vessels and cause damage in the brain.

The $3.6 million National Institute of Aging-sponsored study will be led by University of Rochester Medical Center (URMC) neurologist Giovanni Schifitto, M.D., M.S., and Sanjay B. Maggirwar, M.B.A., Ph.D., with the Department of Microbiology and Immunology.

While it is estimated that more than 1 million Americans are living with HIV, treatments such as combined anti-retroviral therapies (cART) have transformed the disease into a manageable chronic illness. However, as the population living with HIV ages, the long-term effects of both the infection and treatment have given rise to additional health problems.

One such problem is cerebral small vessel disease (CSVD). While the reason CSVD occurs is not clear and may ultimately be the result of a number of factors, a common mechanism is believed to be inflammation. The new study will examine the interaction of two types of blood cells – platelets and monocytes. When these cells become stuck together and form complexes the resulting blockages can lead to a hardening of the arteries.

The brain in particular is highly susceptible to damage when blood flow becomes impaired due its network of tiny vessels. When complexes of platelets and monocytes accumulate in the brain they can promote inflammation which can cause vessels to become leaky, plugged, or burst, resulting in micro-strokes or micro-hemorrhages that damage neurons and other tissue in the brain.

Read More: Study Will Explore Link Between HIV, Micro-Strokes, and Dementia

University Research Awards span a wide range of topics

Wednesday, May 31, 2017

The awards, originally called Provost’s Multidisciplinary Awards, are funded $250,000 every year by the president and matched by the schools for a total of $500,000 annually. They are designed to help researchers advance promising lines of research so that they can obtain external funding.Read More: University Research Awards span a wide range of topics

Scientists Light the Way for Immune System to Attack Cancer

Monday, May 15, 2017

Photo of Dr. Minsoo Kim

The science behind harnessing the immune system to fight cancer is complicated, but a University of Rochester Medical Center laboratory discovered a simple, practical way to use light and optics to steer killer immune cells toward tumors.

In a study published by the online journal Nature Communications, lead author Minsoo Kim, Ph.D., a UR professor of Microbiology and Immunology and a Wilmot Cancer Institute investigator, described his method as similar to “sending light on a spy mission to track down cancer cells.”

Immunotherapy is different from radiation or chemotherapy. Instead of directly killing cancer cells, immunotherapy tells the immune system to act in certain ways by stimulating T cells to attack the disease. Several different types of immunotherapy exist or are in development, including pills called “checkpoint inhibitors” and CAR T-cell therapy that involves removing a patient’s own immune cells and altering them genetically to seek and destroy cancer cells.

The problem, however, is that immunotherapy can cause the immune system to overreact or under-react, Kim said. In addition, cancer cells are evasive and can hide from killer T-cells. Aggressive tumors also suppress the immune system in the areas surrounding the malignancy (called the microenvironment), keeping T cells out.

Read More: Scientists Light the Way for Immune System to Attack Cancer

Federal funding bill boosts support for research, education, health care, and arts

Tuesday, May 9, 2017

Congress has approved legislation which will fund the government through September 30, the end of the 2017 fiscal year. The legislation, which the President has signed into law, has received bipartisan support and in many cases contains welcome increases in funding for federal programs – including research, student aid, health care, and the arts and humanities – that are important to the University.Read More: Federal funding bill boosts support for research, education, health care, and arts

Eric Franklin, Class of 2017, Receives the Ayman Amin-Salem Memorial Fund Award

Friday, May 5, 2017

photo of Eric FranklinCongratulations from the Department of Microbiology to Eric Franklin, class of 2017, for receiving the Ayman Amin-Salem memorial Fund Award. Ayman was a student in the Class of '87 who died in a car accident. His family established this fund in his memory. The prize is given to members of the senior class who best evidences the qualities of good character and good citizenship, such as decency, reliability, responsibility, and congeniality.

Center for AIDS Research Announces Pilot Opportunities

Thursday, April 13, 2017

The University’s Center for AIDS Research announces three new CFAR pilot opportunities. Contact Laura Enders with questions.Read More: Center for AIDS Research Announces Pilot Opportunities

Scientists develop new flu vaccines for dogs

Monday, January 30, 2017

Scientists at the University of Rochester School of Medicine and Dentistry have developed, for the first time, two new vaccines for canine influenza. This research is not only important for improving the health of our furry friends, but for keeping us safe, too. Dogs that have been infected with multiple influenza viruses have the potential to act as "mixing vessels" and generate new flu strains that could infect people. This hasn't happened yet, but experts say it's possible.

Today, veterinarians use vaccines that include inactivated or killed flu virus, but experts say they provide short-term, limited protection. Scientists led by Luis Martinez-Sobrido, Ph.D., associate professor in the department of Microbiology and Immunology created two "live-attenuated" vaccines against H3N8 canine influenza virus, which is currently circulating in dogs in the U.S. Past research shows that live-attenuated vaccines, made from live flu virus that is dampened down so that it doesn't cause the flu, provide better immune responses and longer periods of protection.

Read More: Scientists develop new flu vaccines for dogs

URMC Drug Extends Effectiveness of HIV Therapy

Monday, January 30, 2017

Major Step toward Longer-Lasting HIV Treatment

Image of hand stating Stop HIV

A drug developed at the University of Rochester Medical Center extends the effectiveness of multiple HIV therapies by unleashing a cell’s own protective machinery on the virus. The finding, published today in the Journal of Clinical Investigation, is an important step toward the creation of long-acting HIV drugs that could be administered once or twice per year, in contrast to current HIV treatments that must be taken daily.

The drug, called URMC-099, was developed in the laboratory of UR scientist Harris A. (“Handy”) Gelbard, M.D., Ph.D. When combined with “nanoformulated” versions of two commonly used anti-HIV drugs (also called antiretroviral drugs), URMC-099 lifts the brakes on a process called autophagy.

Normally, autophagy allows cells to get rid of intracellular “trash,” including invading viruses. In HIV infection, the virus prevents cells from turning on autophagy; one of the many tricks it uses to survive. When the brake on autophagy is lifted, cells are able to digest any virus that remains after treatment with antiretroviral therapy, leaving cells free of virus for extended periods of time.

Photo of Dr. Gelbard

Harris A. (“Handy”) Gelbard, M.D., Ph.D.

“This study shows that URMC-099 has the potential to reduce the frequency of HIV therapy, which would eliminate the burden of daily treatment, greatly increase compliance and help people better manage the disease,” said Gelbard, professor and director of UR’s Center for Neural Development and Disease, who has studied HIV/AIDS for the past 25 years. The finding builds on previous research that Gelbard conducted with Howard E. Gendelman, M.D., professor and chair of the Department of Pharmacology/Experimental Neuroscience at the University of Nebraska Medical Center.

Read More: URMC Drug Extends Effectiveness of HIV Therapy

Scientists Develop New Flu Vaccines for Man’s Best Friend

Thursday, January 19, 2017

It's that dreaded time of year – flu season. And we humans aren't the only ones feeling the pain. Dogs can get the flu, too.

Scientists at the University of Rochester School of Medicine and Dentistry have developed, for the first time, two new vaccines for canine influenza. This research is not only important for improving the health of our furry friends, but for keeping us safe, too. Dogs that have been infected with multiple influenza viruses have the potential to act as “mixing vessels” and generate new flu strains that could infect people. This hasn't happened yet, but experts say it's possible.

Today, veterinarians use vaccines that include inactivated or killed flu virus, but experts say they provide short-term, limited protection. Scientists led by Luis Martinez-Sobrido, Ph.D., associate professor in the department of Microbiology and Immunology created two "live-attenuated" vaccines against H3N8 canine influenza virus, which is currently circulating in dogs in the U.S. Past research shows that live-attenuated vaccines, made from live flu virus that is dampened down so that it doesn't cause the flu, provide better immune responses and longer periods of protection.

Read More: Scientists Develop New Flu Vaccines for Man’s Best Friend