Dietrich faculty get grants

•  Kristin Kanthak and Jonathan Woon of political science have received a two-year $246,717 award from the National Science Foundation (NSF) for their project, “Women Don’t Run: An Experimental Analysis of Gender and the Choice to Represent.”

They will investigate the extent to which differences in behavioral decision-making helps to account for the differences in relative frequencies that men and women enter politics and run for public office.

• Christopher Bonneau of political science has received a $5,161 NSF award to conduct a workshop on “The Normative Implications of Empirical Research in Law and Courts.”

The workshop will focus on judicial selection/retention; judicial decision-making; the rule of law; institutional legitimacy, and race, gender and judging.

• Diane Litman, computer science, has received a three-year Institute of Education Sciences grant for “Intelligent Scaffolding for Peer Reviews of Writing.” The award amount is $1,498,939.

GI tumor research funded again

For the seventh consecutive year, a researcher from the University of Pittsburgh Cancer Institute (UPCI), partner with UPMC Cancer Center, has received funding from the GIST Cancer Research Fund, which funds research on gastrointestinal stromal tumors (GISTs). These tumors occur in the gastrointestinal tract and initially can be treated with the targeted therapy drug Gleevec, but rapidly develop resistance to the treatment.

The $120,000 award will support the research of Anette Duensing, pathology faculty member in the School of Medicine. Duensing’s GIST research aims to better understand the biology of GIST responses to Gleevec, as well as the mechanisms underlying drug resistance.

This year’s award pushes the total amount of money Duensing has received from the GIST Cancer Research Fund to more than $720,000.

Engineering awarded grants

• In a first for Pitt, the Department of Energy (DOE) has awarded $1.3 million to the Swanson School of Engineering through DOE’s nuclear energy university programs (NEUP). The grants will support fellowships and research primarily in the Department of Mechanical Engineering and Materials Science.

The grant includes $876,422 for computer modeling research into future generations of high-temperature reactors; $300,000 for a new radiation detection and measurement laboratory, and a $155,000 fellowship for a student pursuing a career in the nuclear field. In addition, a shared $599,802 grant with State University of New York-Stony Brook will help to develop a self-powered sensing and actuation system for nuclear reactors in case of major power failures.

• Jung-Kun Lee of mechanical engineering and materials science has received an NSF grant for his research into solar cell energy conversion. The grant, Solid State Dye Sensitized Solar Cells Using Tunable Surface Plasmons of Core-Shell Particles, is $290,724 over three years.

Coulter program gives 1st grants

Reducing infection post-surgery, regenerating bone, enhancing a surgeon’s delicate touch and effectively treating gum disease are the first projects to receive $340,000 in funding from the Swanson school’s Coulter translational research partners II program.

Created through a $3.54 million grant from the Wallace H. Coulter Foundation last fall, the five-year Coulter program will target development of new technologies to address unmet clinical needs. The award from the Coulter Foundation — one of only six nationwide — is supplemented by $1.5 million in matching funds from the School of Medicine, the Swanson school and the Office of Technology Management.

Medical innovation center grant awarded

Pitt’s Center for Medical Innovation (CMI) has awarded its first seed grants of $25,000 to two teams of investigators. Each team represents a partnership between the engineering school and the Schools of the Health Sciences.

The award winners were:

• Carl Snyderman, Department of Otolaryngology and co-director, UPMC Center for Cranial Base Surgery, and Jeffrey S. Vipperman, Department of Mechanical Engineering and Materials Science, for “SafeDrill: Bi-modal Sensing for Safe and Efficient Neurosurgical Procedures.”

“SafeDrill” is expected to reduce the risk of injury to patients and improve surgical efficiency by providing information to the physician who must penetrate bone in order to treat underlying soft tissue. CMI will fund the analytical and developmental work needed to translate the technology into a clinical instrument.

• Tatum Tarin, Department of Urology, and Kevin Chen, Department of Electrical Engineering, for “A New Approach for Laser Surgery in Kidney.”

Advances in laser optics now make it possible to employ extremely compact endoscopes for diagnostic imaging, tissue characterization and optical ablation therapy in the kidneys through the ureters. CMI will fund the early development of a clinical device suitable for in vivo studies.

Pitt gets 1st I-Corps grant

A team from the McGowan Institute of Regenerative Medicine and the  Department of Bioengineering are launching a six-month translational research effort to develop a commercialization strategy for a novel nerve regeneration treatment. This is Pitt’s first grant from the National Science Foundation Innovation Corps (I-Corps), which provided $50,000 for the project.

The researchers plan to develop a business model for an effective long-gap peripheral nerve repair system with the potential to successfully repair conditions from diabetic neuropathy to battlefield wounds.

Principal investigator is Kacey G. Marra, a faculty member in plastic surgery, bioengineering and the McGowan Institute for Regenerative Medicine, and the laboratory director for Pitt’s Plastic Surgery Research Laboratory. Yen-chih Lin is entrepreneurial lead on the project. The industrial mentor is Pratap Khanwilkar, Coulter program director, faculty member in the Department of Bioengineering and executive-in-residence with the Office of Technology Management.

PSC develops Data Supercell

The Pittsburgh Supercomputing Center (PSC) has developed a cost-effective, disk-based file repository and data-management system called the Data Supercell. This technology is said to provide major advantages over traditional tape-based archiving for large-scale datasets.

The PSC team was composed of Paul Nowoczynski, Jared Yanovich, Zhihui Zhang, Jason Sommerfield, J. Ray Scott and Michael Levine. A patent application is under review.

The Data Supercell is intended especially to serve users of large scientific datasets.

Levine and Ralph Roskies, PSC co-scientific directors, said: “The Data Supercell is a unique technology, building on the increasing cost-effectiveness of disk storage and the capabilities of PSC’s SLASH2 file system. It will go far to enable more efficient, flexible analyses of very large-scale datasets.”

Deployment of the Data Supercell aims to meet expanded data-storage needs posed by rapid evolution toward ever larger quantities of data stored and transferred in many kinds of applications — an evolution frequently termed “big data” — including astrophysics, genomics and vast amounts of Internet data that can be “mined” for commercial purposes.

Departments at Pitt, Carnegie Mellon and Drexel are using the Data Supercell.

Living in the moment may be impossible

“Living in the moment” may be impossible, according to neuroscientists who have pinpointed a brain area responsible for using past decisions and outcomes to guide future behavior.

The study, published in the journal Neuron and based on Pitt research, is the first of its kind to analyze signals associated with metacognition — a person’s ability to monitor and control cognition (a term described by researchers as “thinking about thinking.”)

“The brain has to keep track of decisions and the outcomes they produce,” said Marc Sommer, who did his research as a Pitt neuroscience faculty member and is now at Duke University. “You need that continuity of thought. We are constantly keeping decisions in mind as we move through life, thinking about other things.”

Sommer worked with Paul G. Middlebrooks, who received his PhD in neuroscience at Pitt last year; he now is a postdoctoral fellow at Vanderbilt University. The research team studied single neurons in vivo in three frontal cortical regions of the brain: the frontal eye field (associated with visual attention and eye movements); the dorsolateral prefrontal cortex (responsible for motor planning, organization and regulation), and the supplementary eye field (SEF) involved in the planning and control of saccadic eye movements, which are the extremely fast movements of the eye that allow it to continually refocus on an object.

Subjects performed a visual decision-making task that involved random flashing lights and a dominant light on a cardboard square. Participants were asked to remember and pinpoint where the dominant light appeared, guessing whether they were correct. While neural activity correlated with decisions and guesses in all three brain areas, the putative metacognitive activity that linked decisions to bets resided exclusively in the SEF.

“The SEF is a complex area [of the brain] linked with motivational aspects of behavior,” said Sommer. “If we think we’re going to receive something good, neuronal activity tends to be high in SEF. People want good things in life, and to keep getting those good things, they have to compare what’s going on now versus the decisions made in the past.”

By studying metacognition, Sommer said he reduces the big problem of studying a “train of thought” into a simpler component: examining how one cognitive process influences another.

“Why aren’t our thoughts independent of each other? Why don’t we just live in the moment? For a healthy person, it’s impossible to live in the moment. It’s a nice thing to say in terms of seizing the day and enjoying life, but our inner lives and experiences are much richer than that.”

Funding was provided by Pitt, the joint Pitt-Carnegie Mellon University Center for the Neural Basis of Cognition, the National Institute of Mental Health (NIMH) and the Alfred P. Sloan Foundation.

Decoy shows promise as cancer-fighter

A critical protein that had been deemed “undruggable” can be targeted effectively by using a decoy to fool the body into a cancer-fighting response, according to researchers at the University of Pittsburgh Cancer Institute (UPCI) and the School of Medicine. Results were reported in the August issue of Cancer Discovery.

Activation and increased signaling of a protein known as signal transducer and activator of transcription 3 (STAT3) has been identified in many cancers and is associated with poor prognosis, said senior author Jennifer Grandis, faculty member in otolaryngology, pharmacology and chemical biology in the School of Medicine, and director of the head and neck program at the University of Pittsburgh Cancer Institute (UPCI). Transcription factors such as STAT3 regulate the activity of other genes; in adult tissues, STAT3 triggers the production of other proteins that promote the growth and survival of cancer cells.

“Lab experiments have shown that inhibiting STAT3 activity or function limits the proliferation and survival of a variety of cancer cell lines,” she explained. “But the drugs that have been tested in patients are not selective for STAT3 and haven’t been effective.”

So her research team fooled the STAT3 protein into binding to a harmless decoy that they engineered. Preclinical experiments showed that the strategy was tolerated well and didn’t produce toxic side effects.

The team took biopsies of head and neck cancers in 30 patients who were having surgery to remove the tumors. At the start of the operation, the tumors were injected with either the decoy or a salt-water placebo. After surgery, about four hours after injection, the cancerous tissue that had been taken out of each patient was biopsied again. “We found reduced expression of the STAT3 target genes in tumors that had been treated with the decoy compared to those that got a placebo injection and to pre-treatment samples,” Grandis said.

Co-authors included Pitt researchers from otolaryngology, structural biology, bioengineering, medicine, pharmacology and chemical biology, pathology and biostatistics, as well as researchers from Carnegie Mellon, The Ohio State University and the University of Texas M.D. Anderson Cancer Center.

The project was funded by the National Institute of General Medical Services, the American Cancer Society and the PNC Foundation. Grandis receives support from Bristol-Myers Squibb.

Link found between PTSD, concussion

A Pitt-UPMC study has found that residual symptoms of post-traumatic stress disorder (PTSD) and concussions may be linked in military personnel who endure blast and/or blunt traumas.

With 27,169 participants from the U.S. Army Special Operations Command (USASOC), the study is believed to be the largest of its kind of concussion and PTSD. The study found that USASOC personnel reported clinical levels of PTSD symptoms in 12 percent of concussions from blunt trauma, 23 percent from blast trauma and 31 percent from combination blast-blunt trauma.

By contrast, only 6 percent of those who experienced clinical PTSD never had been diagnosed with a concussion. PTSD reactions were more likely as concussions increased: in 22 percent of personnel after one blast concussion, 29 percent after two and 34 percent after three.

Anthony Kontos, assistant research director for the UPMC sports medicine concussion program and corresponding author on the paper, said: “The findings regarding the clinical PTSD-symptom levels highlight the importance for military medical personnel to screen for and treat PTSD as well as concussion in personnel exposed to concussions, particularly those exposed to multiple-blast traumas. The dose-response relationship between the number of blast concussions and residual concussion and PTSD symptoms supports the notion that exposure to blast head trauma has lingering effects.”

R.J. Elbin, post-doctoral research associate at the School of Medicine, also participated in the research.

The study was funded by the U.S. Special Operations Command biomedical initiatives steering committee.

3-D map offers clues to dark matter, energy

The Sloan Digital Sky Survey III (SDSS-III) has released the largest-ever three-dimensional map of massive galaxies and distant black holes, helping astronomers to better explain the mysterious “dark matter” and “dark energy” that make up 96 percent of the universe.

According to Pitt physics and astronomy faculty member Michael Wood-Vasey, who is the scientific spokesperson for SDSS-III, scientists using the map — Data Release 9 (DR9) — can retrace the universe’s history over the last seven billion years. Wood-Vasey cowrote the DR9 summary paper featured on the arXiv database.

The new DR9 map includes images of 200 million galaxies and spectra measurements of how much light galaxies gives off at different wavelengths — including new spectra of 540,000 galaxies dating from when the universe was half its present age. Researchers say that studying spectra is important because it allows scientists to figure out how much the universe has expanded since the light left each galaxy.

DR9 includes better estimates regarding the temperatures and chemical compositions of more than a half-million stars in the Milky Way. DR9 represents the latest in a series of data releases stretching back to 2001. This release includes new data from the ongoing SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), which eventually will measure the positions of 1.5 million massive galaxies over the past seven billion years of cosmic time, as well as 160,000 quasars — giant black holes feeding on stars and gas — from as long ago as 12 billion years.

SDSS-III is in the middle of its six-year survey. All the newly released data now is available on the DR9 web site at www.sdss3.org/dr9.

Throughout its eight years of operation, the Sloan Digital Sky Survey has obtained deep, multicolor images covering more than a quarter of the sky and has created 3-D maps containing more than 930,000 galaxies and 120,000 quasars.

Life expectancy increases for type 1 diabetics

The life expectancy of people with type 1 diabetes dramatically increased during the course of a 30-year, long-term prospective study, according to Pitt researchers whose findings appear online in the journal Diabetes.

The life expectancy for participants diagnosed with type 1 diabetes in 1965-80 was 68.8 years, a 15-year improvement over those diagnosed in 1950-64, according to the study. The life expectancy of the general U.S. population increased less than one year during the same time period.

Rachel Miller, statistician at the Graduate School of Public Health (GSPH) and lead author of the study, said: “The estimated 15-year life expectancy improvement between the two groups persisted regardless of gender or age at diagnosis.”

The results are based on participants in the Pittsburgh Epidemiology of Diabetes Complications (EDC) study, a long-term prospective study of childhood onset type 1 diabetes, which began in 1986. Participants, who were an average age of 28 when entering the study and 44 at its completion, were diagnosed with type 1 diabetes between 1950 and 1980.

Trevor Orchard, faculty member in epidemiology, pediatrics and medicine, was senior author of the paper.

The 30-year mortality of participants diagnosed with type 1 diabetes in 1965-80 was 11.6 percent — a significant decline from the 35.6 percent 30-year mortality of those diagnosed in 1950-64, according to the study.

Previously known as juvenile diabetes, type 1 diabetes usually is diagnosed in children and young adults.

Other authors of the study included Aaron M. Secrest,  Ravi K. Sharma of behavioral and community health and Thomas J. Songer of epidemiology.

The study was funded by the National Institutes of Health (NIH).

Special ed grants awarded

Three faculty members in special education in the School of Education have received more than $4.3 million for multiple projects from the U.S. Department of Education. This is in addition to $4.4 million in yearly funding from the Pennsylvania Alternate System of Assessment.

All of these projects are aimed an improving the lives of children receiving special education services. Two grants target training and one is focused on enhancing reading education for children with Down syndrome.

Louise Kaczmarek will train early interventionists and early childhood special educators to work with children with autism under age 5, while Chris Lemons is focusing on revising and redesigning the current special education program to develop special education teachers with a secondary content area focus. The final grant was obtained by Naomi Zigmond to prepare five doctoral students to move into faculty positions to serve as special education researchers, trainers of special education teachers and leaders in the field.

Area residents like it here

In the Pittsburgh Regional Quality of Life Survey, a survey of residents of the 32-county region on 10 areas — arts and culture, economy, education, environment, government, health, housing and neighborhoods, public safety, transportation and overall quality of life — respondents gave high marks to regional quality of life and their own happiness.

Despite this, the region has significant problems, including high levels of obesity, glaring quality-of-life differences between African Americans and the overall population, and concerns about public transit and transportation infrastructure. Regarding the Marcellus Shale, while there is considerable environmental concern about it, a greater percentage of people support drilling than oppose it.

• Quality of life. “When asked to rate their lives on a scale of 1-10 for happiness, the mean score was 7.8 for our region, surpassing the national average of 7.4,” said Scott Beach, associate director at the University Center for Social and Urban Research (UCSUR), which conducted the survey with PittsburghTODAY. PittsburghTODAY is an in-depth journalism program that compares Pittsburgh with other regions at PittsburghTODAY.org.

When asked to rate the region in overall quality of life, 81 percent of residents rated it as either good (29 percent), very good (38 percent) or excellent (14 percent). Fewer than 5 percent overall rated regional quality of life as poor.

About 80 percent have been residents of the region for 20 or more years and 90 percent have spent at least 10 years here. And if they plan on moving, it will likely be within the area, where most (84 percent) expect to remain for the next five years.

The social fabric is strong, the survey showed. About 74 percent of residents speak with their neighbors at least several times a month, and 38 percent do so every day. Fewer than 7 percent said they never do. And more than 90 percent of residents agreed to some degree that their neighbors are willing to help others.

Nearly 70 percent of residents rated their children’s education as very good or excellent.

• Marcellus Shale. A strong majority believed the Marcellus Shale natural gas reserves represent an economic opportunity for the region — seven in 10 non-African Americans and six in 10 African Americans saw it as either a significant or moderate economic opportunity, while only one in 10 non-African Americans and one in six African Americans felt it offered very little or no economic opportunity.

At the same time, Marcellus Shale drilling was viewed as an environmental and public health threat to some degree by 83 percent of residents. More than half (55 percent) said drilling was either a significant or moderate environmental and public health threat. And the majority of residents (57.6 percent) supported state government assuming greater environmental oversight.

Extracting the gas was supported by more than 44 percent of residents overall, while one in four opposed the practice.

• African-American disparities. Only 26.5 percent of African Americans rated regional quality of life as excellent or very good, compared to nearly 54 percent of other races. More than 45 percent of African Americans rated the regional quality of life as fair or poor, while 17 percent of other races felt the same way.

Only 14.9 percent of African Americans considered their schools to be very safe, compared to 51.4 percent of residents of other races.

Nearly 5.5 percent of African Americans reported having been a victim of violent crime — almost three times the victimization rate of other races. And African Americans were twice as likely as other races to say local police do a poor job protecting them.

Nearly 18 percent of African Americans said they often or always have trouble paying for housing and other basic necessities — more than twice the hardship rate of other races.

Still, African Americans were more optimistic economically. More than 39 percent felt the national economy would improve, compared with only 23 percent of other races. And 37 percent of African Americans expected the regional economy to get better, compared to 23 percent of other races. More than 41 percent of African Americans overall said their financial situation had improved somewhat or significantly over the past three years, compared with 23.6 percent of residents of other races. Also, 46.7 percent of African Americans living in the city of Pittsburgh reported that their financial situation improved over that time versus 32.6 percent of non-African Americans living in Pittsburgh.

• Health. Nearly two-thirds of regional residents were obese or overweight as determined by their Body Mass Index.

Most residents experienced some stress during the month prior to being interviewed. Nearly 52 percent of residents said they experienced moderate to severe stress, while only one in 10 reported having a stress-free month.

Though there were significant disparities between African Americans and non-African Americans, a preponderant percentage of African Americans reported having health care coverage (84.3 percent versus 90.5 percent for non-African Americans) and nearly the same high percentage stated they did not fail to see a doctor because of the cost (80.7 percent versus 86.4 percent of non-African Americans).

• Transportation. More than two-thirds of residents considered the availability of public transportation a problem. More than half considered it to be a severe or moderate problem, with 73 percent of African Americans seeing it as a severe or moderate problem, versus 49 percent of non-African Americans.

Nearly 67 percent of residents considered the quality of roads and bridges to be either a severe or moderate problem.

The Pittsburgh Regional Quality of Life Survey examined the behaviors and attitudes of more than 1,800 residents, sampling nearly 500 residents of Allegheny County and similar numbers of residents of both the remaining six counties of the Metropolitan Statistical Area and the remaining 25 counties of the greater 32-county region, including counties in Maryland, Ohio, Pennsylvania and West Virginia. The survey also included nearly 400 African American responses.

The survey can be downloaded at www.pittsburghtoday.org/special_reports.html. For copies, contact Emily Craig, edc20@pitt.edu.

Peptide identified that may block hep C virus

GSPH researchers have identified a peptide that may block the entry of the hepatitis C virus (HCV) into the liver, representing a potential target for new drug development.

The results were published in the August issue of Hepatology, the journal of the American Association for the Study of Liver Disease.

Previous research indicated that human apolipoprotein E (apoE), which occurs naturally in the body, forms complexes with HCV, the researchers said. They constructed peptides, dubbed hEP, containing the portions of apoE to which other proteins and lipids typically bind.

They found that hEP blocked the virus from binding to liver cells, preventing infection. That suggests apoE is involved with HCV’s initial entry into the cells, according to lead author Tianyi Wang, faculty member in the Department of Infectious Diseases and Microbiology. It’s possible that hEP thwarts infection because it competes with HCV for a cell surface receptor.

In addition, researchers determined that the ability of hEP to block the virus appears to be dependent on the peptide’s length and sequence. Shorter versions could not stop infection, possibly because the shape of the proteins — and thus their binding ability — was altered.

“Our findings highlight the potential of developing peptides that mimic hEP as new hepatitis C viral inhibitors,” said Wang.

Worldwide, more than 170 million people are infected with the hepatitis C virus, which often is asymptomatic and can cause severe liver disease and liver cancer. Existing treatments are effective in only 40-80 percent of patients and can cause severe side effects. There is no cure for HCV.

Pitt collaborators included Shufeng Liu and Kevin D. McCormick, Department of Infectious Diseases and Microbiology, and Ting Zhao, Department of Pathology, School of Medicine.

NIH funded the research.

Urine test indicates bone fracture risk

A simple urine test can indicate a premenopausal woman’s risk of bone fractures as she ages, according to Pitt epidemiologists.

Women in their 40s and early 50s had a 59 percent greater risk of bone fracture as they aged when they had above-normal levels of N-telopeptide (NTX) – the byproduct of bones breaking down — in their urine, compared with women who had low NTX levels. When women with high NTX levels also had a low spinal bone density measurement, their risk of fracture increased nearly three-fold.

The study is the first to look for signs of bone breakdown in younger, premenopausal women in an effort to determine if such signs can predict the risk that these women will suffer fractures as they age.

The results were published in the online edition of Menopause, the journal of The North American Menopause Society. The report will be published in the journal’s November print issue.

“Bone fractures — particularly in the hip, wrist and back — have serious consequences, including disability and death,” said lead author Jane Cauley, faculty member in epidemiology. “Knowing a woman’s risk of fracture can help doctors determine the best course of action to protect her bones as she enters menopause, a time when estrogen deficiency negatively affects skeletal health.”

By the time a woman turns 50, her risk of a fracture at some point in the remainder of her life is estimated to be at least 40 percent. Fractures are more common for these women than heart attacks, strokes and breast cancer combined.

During menopause, bone remodeling increases, leading to an imbalance between bone formation and bone resorption, or the process by which bones are broken down and their minerals are returned to the blood. This remodeling persists for several years and is associated with an increased rate of bone loss, making it easier for bones to fracture.

Cauley and her colleagues used data from 2,305 premenopausal or perimenopausal women aged 42-52 collected as part of the Study of Women’s Health Across the Nation (SWAN).

Pitt collaborators included Michelle E. Danielson, Leslie Meyn and Kristine Ruppert of epidemiology; Yuefang Chang, neurological surgery, and Beth A. Prairie, obstetrics, gynecology and reproductive sciences, School of Medicine.

The research was supported by NIH, the Department of Health and Human Services, the National Institute of Nursing Research, the Department of Defense (DoD), the Iris Cantor-UCLA Women’s Health Center and the UCLA Center of Excellence in Women’s Health.

Pitt part of effort to improve drug safety

School of Medicine researchers have been awarded grants to create micro-models of the liver and an arthritic joint as part of a national effort to build 3-D chips of cells and tissues that could provide a more rapid and accurate method of predicting toxicity of experimental therapies, as well as foster greater understanding of myriad diseases.

Of the 17 projects being funded by NIH, two will be led by Pitt researchers and could receive more than $10 million over the next five years. NIH plans to commit up to $70 million over five years for the program. Other awardees were Johns Hopkins, Harvard and Duke.

Arthur S. Levine, senior vice chancellor for Health Sciences and dean of the School of Medicine, said: “Tissue chips could provide a more accurate and less expensive way of testing new drugs and reduce our reliance on animal studies, which often don’t reliably reflect toxicity profiles later seen during human testing.”

The Pitt projects are:

• 3-D Micro-Liver: D. Lansing Taylor,  Allegheny Foundation Professor of Computational and Systems Biology and director, University of Pittsburgh Drug Discovery Institute, will lead a team at Pitt and Massachusetts General Hospital to create a three-dimensional microfluidic structure made entirely of human cells that will mimic the acinus, the smallest functional unit of the liver.

The team also will develop a panel of sentinel “biosensor cells” that will indicate liver toxicity with exposure to different drugs.

• 3-D Micro-Arthritic Joint System: Rocky Tuan, the Arthur J. Rooney Sr. Professor of Sports Medicine and executive vice chair for research, Department of Orthopaedic Surgery, will lead a team to create a tissue chip that includes stem cell-produced bone and cartilage cells that simulate joint surfaces to better understand how arthritis develops and how to prevent it.

“This system will allow us to explore the effects of not only inflammatory molecules and the wear-and-tear of aging on the entire joint, but also mechanical injuries, such as a hit or a sprain, both immediately and over time in molecular detail,” said Tuan, who also is director of the Center for Military Medicine Research, director of the Center for Cellular and Molecular Engineering in the Department of Orthopaedic Surgery, and co-director of the McGowan Institute for Regenerative Medicine.

The tissue chips program is the result of collaboration among NIH, the Defense Advanced Research Projects Agency (DARPA) and the U.S. Food and Drug Administration.

“Serious adverse effects and toxicity are major obstacles in the drug development process,” said Thomas R. Insel, NCATS acting director.

“With innovative tools and methodologies, such as those developed by the tissue chips program, we may be able to accelerate the process by which we identify compounds likely to be safe in humans, saving time and money, and ultimately increasing the quality and number of therapies available for patients.”

Taylor and Tuan also will receive support from the University of Pittsburgh Clinical and Translational Science Institute.

Grant to study improvements for those who use wheelchairs

Researchers from the School of Medicine and UPMC will lead a five-year, multi-site project aimed at improving the lives of people with spinal cord injuries. The study will use Internet-based training and group sessions to hone the skills of wheelchair users and prevent wheelchair failures.

Among the other groups involved in the research are: the Northern New Jersey Spinal Cord Injury System; the Midwest Regional Spinal Cord Injury Care System, and the South Florida Spinal Cord Injury System.

“This grant will start to tackle problems related to insurance cutbacks that have negatively impacted individuals with spinal cord injuries,” said Michael Boninger, chair of the Department of Physical Medicine and Rehabilitation, Pitt School of Medicine. “Because they spend less time in the hospital after their injuries, they never learn how to effectively use and maintain their wheelchairs.”

Drug could help prevent TB reactivation

Reactivation of latent tuberculosis infection could be better prevented if a drug that is effective against bacteria in low-oxygen environments is added to the treatment regimen, according to School of Medicine research published in the online Proceedings of the National Academy of Sciences.

Pulmonary TB is spread through infected air droplets, said senior author JoAnne L. Flynn, faculty member in the Department of Microbiology and Molecular Genetics, School of Medicine. People can develop active TB with cough, fever, night sweats and fatigue, but most develop an asymptomatic “latent” infection where the bacteria can remain in the lung tissue walled off in a lesion called a granuloma. In some, particularly the elderly or immune-compromised, the infection can reactivate years later.

“An estimated 2 billion people worldwide are latently infected with TB, so it’s imperative to have treatment strategies that can prevent the disease from becoming active again,” Flynn said.

Active TB that is not resistant to antibiotics is treated with a so-called “short course” of two months of the drugs isoniazid (INH), rifampin (RIF), pyrazinamide and ethambutol, followed by four more months of INH and RIF. Latent infection is treated with nine months of INH. It is challenging for patients to complete the treatment, so new drugs that act more quickly would be helpful, noted Flynn, who also is an associate member of the Center for Vaccine Research.

Previous research has shown that the TB bacilli that can survive low-oxygen conditions are not susceptible to INH. Yet the caseous (“cheese-like”) granulomas commonly seen in human infection have areas of tissue death, or necrosis, associated with a hypoxic environment. That led the team to examine whether metronidazole (MTZ), an antibiotic that is known to be effective against non-replicating bacteria in low-oxygen settings, would be better able to eradicate the TB bacilli contained in the granuloma.

The researchers found that in a macaque model of TB, two months of MTZ alone was as effective as two months of INH and RIF at preventing reactivation of the infection induced by an agent called anti-tumor necrosis factor antibody, which triggered disease in most of the untreated animals. Also, adding MTZ to an INH and RIF regimen reduced bacterial burden in monkeys with active TB within two months.

Flynn said, “The next step is to find better drugs that work in these hypoxic areas of granulomas because MTZ can be difficult to tolerate over an extended time.”

Pitt co-authors included Philana Ling Lin, Department of Pediatrics; Paul J. Johnston, Department of Microbiology and Molecular Genetics, and Christopher Janssen and Edwin Klein of the Division of Laboratory Animal Research.

The project was funded by the Bill and Melinda Gates Foundation, the Otis Foundation and National Institute of Allergy and Infectious Diseases.

Most U.S. bars that are smoke-free allow hookahs

Nearly 90 percent of the largest U.S. cities that prohibit cigarette smoking in bars have exemptions that permit hookah smoking, according to a School of Medicine study published in the American Journal of Public Health.

Hookah tobacco smoking is becoming more common in the United States, especially among college-aged students, but few people are aware of the health risks, said Brian Primack, faculty member in medicine and pediatrics and director of the Program for Research on Media and Health at Pitt’s School of Medicine, who led the study.

The World Health Organization found that a hookah smoker may inhale as much smoke during one smoking session as someone would from smoking 100 cigarettes, and studies have suggested secondhand hookah smoke also is a concern.

Researchers found that 73 of the 100 largest cities in the United States have laws that prohibit cigarette smoking in bars; 69 of those cities have exemptions that may allow hookah smoking. Many of the policies were enacted before hookah smoking became popular.

Pitt collaborators on the study were Mary V. Carroll and Michael J. Fine, School of Medicine; Kevin H. Kim, School of Education, and Julie M. Donohue, GSPH.

The study was funded by the National Cancer Institute.

Social work faculty awarded grants

• Shaun Eack is the co-principal investigator on three grants.

The first, a study looking at brain imaging cognitive enhancement and early schizophrenia, is being funded by NIMH for almost $3.2 million over five years.

The study will examine the effects of a novel cognitive rehabilitation program, Cognitive Enhancement Therapy (CET),  on the brain in individuals with early course schizophrenia.

An 18-month clinical trial of CET will use integrated neuroimaging techniques to assess brain function, structure and connectivity during the course of CET treatment, as well as the predictive contribution of brain reserves to treatment response.

A one-year post-treatment durability study will be conducted to examine the degree to which neurobiologic, cognitive and functional effects can be sustained post-treatment in early course schizophrenia patients.

Also participating in the research is social work faculty member Christina Newhill.

Eack and Nancy Minshew, faculty member in psychiatry, School of Medicine, are co-PIs on a $1.4 million DoD-funded clinical trial of cognitive enhancement therapy for adults with autism spectrum disorders.

The study will evaluate the efficacy of CET for improving cognitive and behavioral outcomes in autism spectrum disorders, examine the six-month post-treatment durability of CET effects in adults with autism, and examine the impact of CET on neurobiologic processes and brain connectivity in these disorders.

Eack also is co-PI on an NIMH grant of $720,000 to conduct an initial randomized-controlled trial of computer-based neurocognitive and group-based social-cognitive remediation in individuals with 22q11.2 deletion syndrome. This syndrome is caused by the deletion of a small piece of chromosome 22. The features of this syndrome vary widely, even within families.

• Lovie Jackson is the principal investigator on an NIH grant.

She will conduct research with adolescents, caregivers and health care providers in order to develop a web/tablet-based intervention to improve the feasibility of primary care screening for adolescent mental disorders, provide brief youth-centered mental health education to engage adolescents and caregivers, and offer health care providers guidance on youth mental health care referral needs via provider advice sheets.

She will pilot test the intervention in urban health centers.

Other Pitt researchers involved in the project are Duncan Clark, David J. Kolko, Elizabeth Miller, Mary Ann Sevick and Galen Switzer, all of the School of Medicine; Larry Davis, social work; Bambang Parmanto, School of Health and Rehabilitation Sciences, and Kevin Kim, School of Education.

• John Wallace has received an NIH sub-award from the University of Michigan for “Monitoring the Future: Drug Use and Life Styles of American Youth.”

The study will:

— examine within and between group racial/ethnic differences and similarities in patterns, trends and correlates of drug-related attitudes, beliefs and behaviors;

— conduct racial/ethnic and gender-specific analyses that seek to identify whether risk and protective factors found to be important for white males and females also are important correlates and predictors for non-white youth, and

— investigate the mechanisms through which individual and contextual-level religiosity influences substance use.

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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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