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March 20, 2014

Research Notes

Fu receives career award

FuFreddie Fu has received the Elizabeth Winston Lanier Award for his career contribution to anterior cruciate ligament (ACL) reconstruction and advances in patient care. Considered the Nobel Prize of orthopaedic research, the award was bestowed by the Kappa Delta Sorority along with the Orthopaedic Research and Education Foundation. It was presented to Fu in New Orleans at the 2014 annual meeting of the American Academy of Orthopaedic Surgeons (AAOS).

Fu, the David Silver Professor and chair of the Department of Orthopaedic Surgery and founder of the UPMC Center for Sports Medicine, also will receive honors in Europe and Asia over the next four months. The European Society of Sports Traumatology, Knee Surgery and Arthroscopy is scheduled to present its highest honor to Fu by making him a lifetime honorary member and a member of its Hall of Fame — the first person from Pennsylvania, the second from the United States and only the fourth inductee to date. He was unanimously endorsed for the award by the eight-member board of directors.

In July, the Japanese Orthopaedic Society of Knee, Arthroscopy and Sports Medicine will make Fu only the fourth surgeon — and second from the Western Hemisphere — recognized with the Masaki Watanabe Award for international achievement in arthroscopic surgery.

In the past quarter-century, roughly 600 fellows from around the world have come to Pittsburgh to train. In addition to caring for patients, overseeing orthopaedics and sports medicine, and serving as the head team physician for Pitt athletics, Fu also remains committed to research and education. He is among the first eight faculty members of the School of Medicine to receive Pitt’s designation as a Distinguished Service Professor.


Researchers win Cozzarelli Prize

Researchers at the School of Medicine and Magee-Womens Research Institute (MWRI) have been awarded the Cozzarelli Prize in the biomedical sciences. The award was for a July 2013 paper in the Proceedings of the National Academy of Sciences (PNAS) that showed the cells of the placenta may have a unique ability to prevent viruses from crossing from an expectant mother to her fetus and can transfer that trait to other kinds of cells.

Senior authors Yoel Sadovsky and Carolyn Coyne and their research team will be honored April 27 at a ceremony in Washington, D.C., during the National Academy of Sciences annual meeting.

Sadovsky serves as Elsie Hilliard Hillman Chair of Women’s Health Research, faculty member in the School of Medicine and MWRI director, while Coyne is a faculty member in the Department of Microbiology and Molecular Genetics and an MWRI member.

Co-authors for the paper who also will be honored include Elizabeth Delorme-Axford, Rogier B. Donker, Jean-Francois Mouillet, Tianjiao Chu, Avraham Bayer, Yingshi Ouyang, Tianyi Wang, Donna B. Stolz, Saumendra Sarkar and Adrian E. Morelli.

The research team studied human trophoblast cells in the lab, exposing them to a panel of viruses. Unlike nonplacental cells, trophoblasts were resistant to viral infection, but that trait was not a result of an inability of viruses to bind or enter the cells. When the fluid in which the trophoblasts were cultured was transferred to nonplacental cells, such as those that line blood vessels, they became resistant to viral infection as well.

The team found that when the fluid was exposed to sound waves in a process called sonication, viral resistance no longer was transferred to nonplacental cells. This finding led them to take a closer look at exosomes, tiny spheres called nanovesicles that are secreted by trophoblasts and are sensitive to sonication. Fragments of genetic material called microRNAs contained within the exosomes, as well as lab-synthesized mimics of them, were able to induce autophagy, a mechanism of prolonged cellular recycling and survival. Blocking autophagy at least partially restored the cells’ vulnerability to viral infections.

The Cozzarelli Prize is named for the late PNAS editor-in-chief Nicholas R. Cozzarelli and acknowledges papers that reflect scientific excellence and originality.


Study shows excessive deer populations hurt native plant biodiversity

deerA research team led by Susan Kalisz, a faculty member in the Department of Biological Sciences, published a paper online in the Proceedings of the National Academy of Sciences that takes a long view on why invasive garlic mustard plants thrive to the detriment of native species.

The study, initiated in 2003 at the Trillium Trail Nature Reserve in Fox Chapel, concludes that an overpopulation of deer (the density of deer in the U.S. is about four-10 times what it was prior to European settlement of North America) is the primary reason garlic mustard is crowding out native plants, such as trillium, which are preferred food for wild deer.

Garlic mustard (Alliaria petiolata) is native to Europe and Asia and is inedible by deer standards. It was brought to the United States — Long Island, N.Y., specifically — in the 1860s for use as a kitchen herb.

Instead it became a menace, colonizing forest floors in the eastern U.S. and Canada. It has been found in Washington state, Utah and British Columbia, achieving the dubious distinction of being one of very few non-native plants to successfully invade forest understories. The persistence of garlic mustard greatly reduces forest biodiversity.

To study the effect of rampant deer on trillium and garlic mustard populations, Kalisz and colleagues established multiple 196-square-meter plots in the forest, half of which were fenced to exclude deer. Years of observation and hours of statistical analysis later, Kalisz and her colleagues found that in plots where deer were excluded, the trillium population is increasing and the garlic mustard population is trending toward zero.

This study shows that two major ecological and management problems are linked: an excess of deer in temperate forests and an invasion of these forests by exotic plants.


3-D tissue repair structures?

Researchers from the Swanson School of Engineering and the McGowan Institute for Regenerative Medicine are proposing that if 3-D printers, or additive manufacturing, can produce custom replacement parts for machines, the same process could be used to create biodegradable tissue repair structures for the human body.

“Additive Manufacturing of Biomedical Devices From Bioresorbable Metallic Alloys for Medical Applications” was one of 15 projects selected by America Makes, the National Additive Manufacturing Innovation Institute, as part of its second call for additive manufacturing (AM) applied research and development projects. The project’s principal investigator is Prashant Kumta, a faculty member in the Swanson school and the School of Dental Medicine; co-principal investigator is Howard Kuhn, also from the Swanson school. Patrick Cantini, director of scientific collaborations for UPMC and director of the McGowan Institute’s Center for Industry Relations, will serve as project manager.

Corporate partners include ExOne, Magnesium Elektron and Hoeganaes Corp. The $590,000 contract is for an 18-month period.

In addition to precise modeling of a body structure, additive manufacturing allows for the use of biodegradable alloys that serve as functional scaffolds for inducing cells to grow as well as platforms for delivering biological molecules and antibiotics, rather than as artificial implants.

A process called “sintering” cures the scaffolds to provide structural integrity to the bonded particles. During this phase of the research, the scaffolds will be evaluated for biocompatibility, bioresorption and mechanical properties. Some of the biomedical devices such as bone fixation plates and screws, as well as tracheal stents, will be produced in preparation for later clinical studies.


Researcher receives AHA fellowship

While the development of artificial vascular grafts has advanced, one of the drawbacks is a high rate of aneurysms, leading to rupture and massive bleeding. But engineers at the Swanson school are exploring the use of new polymers in arterial replacements to better prevent aneurysm formation as they remodel into “neoarteries.”

Arturo Valentin is the recipient of an American Heart Association (AHA) Great Rivers Affiliate postdoctoral fellowship for “A Predictive Computational Tool for Creating Tissue-engineered Arteries.” Valentin is a postdoctoral researcher with a focus on mechanobiology in the Swanson school’s Department of Mechanical Engineering and Materials Science.

Valentin notes that by studying the underlying biological mechanisms at work in neoartery formation, researchers can develop a more effective graft that reduces risk of aneurysms.

“This AHA fellowship will support our research to build replacement arteries utilizing advanced synthetic polymers as grafts that better treat patients with peripheral artery disease or who must undergo cardiac bypass surgery,” he said.

Valentin believes that over the next several years his research will move to clinical trials in humans and “ultimately help bring much improved arterial replacements to patients.”


IS profs win best paper award

School of Information Sciences faculty members Leanne Bowler and Eleanor Mattern received the Lee Dirks Best Paper Award at iConference 2014 for “Developing Design Interventions for Cyberbullying: A Narrative-based Participatory Approach.” Co-authored with Cory Knobel of the University of California-Irvine, the paper presented a user-generated framework for designing affordances that would counter acts of cyber bullying on social media sites. Using narrative inquiry as a research methodology, the authors invited two focus groups to map out a cyber bullying story and overlay it with a set of design recommendations that, in the participant’s view, might alleviate mean and cruel behavior online.


2 faculty win Google awards

Rosta Farzan, faculty member in the School of Information Sciences, and Diane Litman, a faculty member in the Department of Computer Science, won 2014 Google Faculty Research Awards. Of the 691 proposals from 46 countries, 115 projects were funded.

Farzan’s award was for research in human-computer interaction.

Litman’s award was for her work in natural language processing.

The Google Research Awards provide one-year unrestricted awards to support full-time faculty pursuing research in areas of interest to Google’s mission.


Swanson faculty member honored

The Materials Research Society (MRS), an international, interdisciplinary organization of materials researchers from academia, industry and government, recently named Anna C. Balazs among its 2014 class of 22 new fellows. Balazs is a faculty member in the Swanson school and a researcher in the computational design of chemo-mechanically responsive gels and composites.

Balazs was recognized “for pioneering contributions to the prediction of materials behavior, ranging from nanocomposites to self-healing materials to oscillating gels, through the development of novel computational models.”


Pitt prof part of team showing how identical cells differentiate

Cell-DivisionBritish mathematician Alan Turing’s accomplishments in computer science are well known; he’s the man who cracked the German Enigma code, expediting the Allies’ victory in World War II. He also had a tremendous impact on biology and chemistry. In his only paper in biology, Turing proposed a theory of morphogenesis, or how identical copies of a single cell differentiate, for example, into an organism with arms and legs, a head and tail.

Now, 60 years after Turing’s death, researchers from Pitt and Brandeis University have provided the first experimental evidence that validates Turing’s theory in cell-like structures.

The team published its findings in the Proceedings of the National Academy of Sciences on March 10.

In 1952, Turing was the first to offer an explanation of morphogenesis through chemistry. He theorized that identical biological cells differentiate and change shape through a process called intercellular reaction-diffusion. In this model, chemicals react with each other and diffuse across space — say between cells in an embryo. These chemical reactions are managed by the interaction of inhibitory and excitatory agents. When this interaction plays out across an embryo, it creates patterns of chemically different cells. Turing predicted six different patterns could arise from this model.

At Brandeis, researchers  created rings of synthetic, cell-like structures with activating and inhibiting chemical reactions to test Turing’s model. G. Bard Ermentrout, a faculty member in Pitt’s Department of Mathematics, undertook mathematical analysis of the experiments.

The researchers observed all six patterns plus a seventh not predicted by Turing.

In addition, they noticed that, as Turing theorized in the 1950s, the once identical cell-like structures, now chemically different, also began to change in size due to osmosis. This may explain how some cells, further down the development assembly line, become large egg cells or tiny sperm cells.


Swanson profs get NSF award for undergrad research program

The National Science Foundation awarded Department of Chemical and Petroleum Engineering faculty members Joe McCarthy and Cheryl Bodnar a grant of $383,431 to lead a research experience for undergraduates (REU) program. The program will expose some students to the research going on in the department.


NIH renews grant for research into viruses, cancer pathways

The National Institutes of Health (NIH) has renewed a grant of more than $2 million for Patrick Moore, director of the molecular virology program at the University of Pittsburgh Cancer Institute (UPCI), to continue research into the newest human cancer virus causing most Merkel cell carcinomas.

A team led by Moore and Yuan Chang discovered the Merkel cell polyomavirus in 2008, the seventh human cancer virus identified and the second discovered by Moore’s group under the original NIH grant that expires March 31. The new grant will fund the research through March 2019.

Moore, Chang and their colleagues identified a protein that allows the usually harmless polyomavirus to transform healthy cells into Merkel cell carcinoma, a rare but deadly skin cancer. They hope their work — which emphasizes the importance of fundamental basic science research to medical progress — soon can be translated into human clinical trials.

“Viruses are an important model for cancer research,” Chang said. “We’ve found that it may be possible to kill cancerous tumors by targeting the pathways these viruses use. That’s significant when you consider that 20 percent of all cancers are related to infectious diseases.”


Analysis guides hospital programs in community health

An analysis led by the Graduate School of Public Health offers insights for nonprofit hospitals in implementing community health improvement programs.

In a special issue of the Journal of Health Care for the Poor and Underserved that focuses on the Affordable Care Act (ACA), a multidisciplinary team of Pitt researchers explored published research on existing community benefit programs at U.S. hospitals and explained how rigorous implementation of such programs could help hospitals both meet federal requirements and improve the health of the populations they serve.

Lead author Jessica Burke, a faculty member in the Department of Behavioral and Health Sciences, and her colleagues note that “community health needs assessments,” which are required by the ACA and rely on large surveys and input from community stakeholders, including minorities and underserved populations, can provide information to help guide the development of community benefit programs, as well as provide data needed to assess their impact.

By evaluating 106 scientific articles detailing hospital-based community benefit programs, Burke and her colleagues were able to categorize the programs into those based in the hospital and those administered at a community facility, finding that the programs were split almost evenly.

Hospital-based programs typically included preventative screenings or health education. Outside the hospitals, the programs included hospital after-care and benefits and coverage counseling, but largely were community-based programs, either with or without a community partner organization, such as a local school or community center.

According to senior author Everette James, faculty member in the Department of Health Policy and Management, the analysis reinforces the value hospitals and health systems can derive from partnering with public health professionals to design their community health needs assessments and determine the best community benefit programs to address those needs.

UPMC worked with Burke and her colleagues at the public health school and Pitt’s Health Policy Institute to conduct community health needs assessments for 13 of its hospitals, which the health system then used to guide its community benefit programs and set community health improvement goals.


High intake of fish oil may benefit cardiovascular health

Pure Fish OilEating fish in amounts comparable to those of people living in Japan seems to impart a protective factor that wards off heart disease, according to an international study funded by NIH and led by the Graduate School of Public Health.

Middle-aged Japanese men living in Japan had a lower incidence of coronary artery calcification, a predictor of heart disease, than middle-aged white men living in the United States, likely due to the significantly higher consumption of omega-3 fatty acids found in fish. The findings were published in the March 6 issue of the journal Heart.

Marine-derived omega-3 fatty acids, which are found in fish, especially oily fish, as well as in squid and krill, may help to reduce inflammation and slow the formation of fatty plaques in arteries.

Researchers at Pitt, including lead author and public health faculty member Akira Sekikawa, partnered with scientists in Japan, Hawaii and Philadelphia to follow nearly 300 men for five years, tracking multiple factors that affect cardiovascular health. These factors included cigarette smoking, alcohol consumption  and the level of cholesterol in the blood, as well as their rates of diabetes and high blood pressure.

After accounting for risk factors for heart disease, the U.S. men had three times the incidence of coronary artery calcification as the Japanese men. Meanwhile, the levels of marine-derived omega-3 fatty acid in the blood were more than 100 percent higher in the Japanese than in the U.S. men.

The average dietary intake of fish by Japanese people living in Japan is nearly 100 grams each day, which the American Heart Association considers 1.5 servings.

The average American only eats about seven-13 grams of fish a day.

Heart disease is the leading cause of death in the U.S. and globally, according to the World Health Organization. However, Japan bucks this trend, with cancer as the leading cause of death.


Biomarkers can warn of deadly kidney illness

A national, multicenter study led by Pitt researchers found biomarkers that can tell a physician if a patient is at risk for acute kidney injury (AKI), a condition that often affects those in intensive care and can occur hours to days after serious infections, surgery or taking certain medications.

The results, available online in the American Journal of Respiratory and Critical Care Medicine, validates previous research from this group identifying the biomarkers, known as tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP-7) in urine, that signal the kidneys are stressed and at risk for failing. The biomarkers are indicators of cell damage, a key component in the onset of AKI.

Senior investigator John Kellum of the Department of Critical Care Medicine and director of the Center for Critical Care Nephrology, said: “AKI remains one of the most common complications among critically ill patients, affecting up to 7 percent of all hospitalized patients, yet we lack a precise and reliable method of discerning risk. By providing actionable information, this study advances the translation of biomarker technology into routine practice.”

Investigators enrolled 420 critically ill patients. The primary analysis assessed the ability of the biomarkers to predict moderate to severe AKI within 12 hours of test measurement. To confirm the findings, a committee of three independent expert nephrologists who were blinded to the results of the test reviewed the cases to diagnose AKI.

AKI is asymptomatic, particularly in the early stages when intervention is most beneficial. The incidence of AKI is high among critically ill patients, with up to 50 percent developing some degree of AKI during their illness, increasing the risk of death due to kidney failure.

Co-authors of the study include researchers from 23 medical centers nationwide. The study was sponsored by Astute Medical. Kellum has received grant support and consulting fees from Astute Medical.

—Compiled by Alex Oltmanns


The University Times Research Notes column reports on funding awarded to Pitt researchers as well as findings arising from University research.

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