University Times

Tax check-off aids Pitt research

Faculty members Hannah Rabinowich of immunology and Richard Steinman of medicine and pharmacology are among the grant winners of the 2010 Income Tax Check-Off for Breast and Cervical Cancer Research.

The check-off program enables taxpayers to donate all or part of their Pennsylvania income tax refund to breast and cervical cancer research by checking “yes” on line 35 of the PA 40 tax form.

Rabinowich and Steinman each received a $50,000 grant. They plan to use them to investigate how and why breast cancer recurs after remission.

Key brain areas are linked

School of Medicine researchers have found new evidence that the basal ganglia and the cerebellum are linked as an integrated functional network. The findings are available online in the Proceedings of the National Academy of Sciences.

Neurobiology faculty member Peter L. Strick, who is co-director of the medical school’s Center for the Neural Basis of Cognition, said, “The basal ganglia and the cerebellum are two major subcortical structures that receive input from and send output to the cerebral cortex to influence movement and cognition.”

Each subcortical structure houses a unique learning mechanism. Basal ganglia circuits are thought to be involved in reward-driven learning and the gradual formation of habits. In contrast, cerebellar circuits are thought to contribute to more rapid and flexible learning in response to errors in performance.

“In the past, these two learning mechanisms were viewed as entirely separate, and we wondered how signals from the two were integrated,” said Strick, senior author of the research. “Using a unique method for revealing chains of synaptically linked neurons, we have demonstrated that the cerebellum and basal ganglia are actually interconnected and communicate with each other.”

This result not only has important implications for the normal control of movement and cognition, but it also helps to explain some puzzling findings from patients with basal ganglia disorders.

For example, the degeneration of a specific set of neurons and their synapses in the basal ganglia is known to be the cause of Parkinson’s disease. However, one of the treatments for the resting tremor that characterizes the disease is to interrupt signals from the cerebellum to the cerebral cortex.

Imaging studies of patients with Parkinson’s disease and patients with dystonia, another disorder thought to be of basal ganglia origin, show abnormal increases in activity in the cerebellum.

“Our findings provide a neural basis for these findings,” Strick said. “In essence, the pathways that we have discovered may enable abnormal signals from the basal ganglia to disrupt cerebellar function. The alterations in cerebellar function are likely to contribute to the disabling symptoms of basal ganglia disorders. Thus, a new approach for treating these symptoms might be to attempt to normalize cerebellar activity.”

Andreea C. Bostan, a doctoral student in Pitt’s Center for Neuroscience, and Richard P. Dum of the Center for the Neural Basis of Cognition, co-authored the paper.

The study was funded by the Department of Veterans Affairs and the National Institutes of Health.

Comp sci adds another CAREER award

Faculty member Liz Marai is the computer science department’s most recent National Science Foundation CAREER award recipient.

Three other faculty in the 19-member department currently have active CAREER awards. The grant is known as the NSF’s most prestigious award for junior faculty.

Under this grant, Marai will investigate human anatomy and dynamics to make progress in replicating human articulation capabilities.

In her project, sampled dynamic motion data will be used to infer parameters such as soft-tissue geometry and behavior. The cross-disciplinary project is driven by specific problems in orthopaedics and human character animation, although its focus fundamentally lies on computational and automated analysis tools.

The broad impact of the project includes applications in biology, bioengineering, ergonomics, evolutionary biology and robotics.

The research plan develops computational tools for capturing dynamic skeletal motion from medical images, for inferring biological shape and behavior from dynamic motion information and for representing and calculating with these data.

The project aims to yield a set of human-anatomy based models of articulations to aid orthopaedists’ understanding of articulation injury and disease, to lead to improved diagnosis and medical treatment and to improve the realism of digital character animation.

Gum disease, cavity gene variants found

Certain genetic variations may be linked to higher rates of tooth decay and aggressive periodontitis, according to two recently published papers by Pitt dental school researchers and their collaborators.

The papers’ senior author, oral biology faculty member Alexandre R. Vieira, and colleagues found that the rate of dental caries was influenced by individual variations, or polymorphisms, in a gene called beta defensin 1(DEFB1), which plays a key role in the first-line immune response against invading germs. The findings are available online in the Journal of Dental Research.

“We were able to use data gathered from our Dental Registry and DNA Repository, the only one of its kind in the world, to see if certain polymorphisms were associated with the development of caries,” said Vieira, who also is affiliated with Pitt’s Department of Pediatric Dentistry, the Center for Craniofacial and Dental Genetics, the Department of Human Genetics and the Clinical and Translational Sciences Institute.

“This could help us find new ways to treat people who are particularly susceptible to tooth decay, a problem that afflicts millions of Americans.”

For the study, the researchers analyzed nearly 300 anonymous dental records and accompanying saliva samples from the registry, assigning each case a score based on the presence of decayed teeth, missing teeth due to caries and tooth fillings, as well as a score based on decayed teeth, missing teeth and filled surface of a tooth.

In general, individuals with fewer caries have lower scores on both.

Saliva samples contained one of three variants, dubbed G-20A, G-52A and C-44G, of the DEFB1 gene. Individuals who carried a G-20A copy had scores that were five times higher than in people who had other variants. The G-52A polymorphism was associated with lower scores.

“It’s possible that these variations lead to differences in beta defensin’s ability to inhibit bacterial colonization,” Vieira said. “In the future, we might be able to test for these polymorphisms as clinical markers for caries risk.”

In a second paper, published earlier this month in PLoS One, Vieira, Pitt colleagues and collaborators in Brazil studied saliva samples of 389 people in 55 families to look for genetic links to aggressive periodontitis, which is rapid and severe destruction of the gums and bone that starts at a young age and is thought to be more common in Africans and those of African descent.

Brazil’s population is composed primarily of Caucasians of Portuguese ancestry, Africans and native Indians.

They found hints of an association between the disease and the FAM5C gene.

While further testing did not find any mutations or polymorphisms that bore out a relationship, other experiments showed elevated levels of FAM5C expression, or activation, in areas of diseased periodontal tissue compared to healthy tissue.

“The FAM5C gene recently was implicated in cardiovascular disease, in which inflammation plays a role, just as in periodontitis,” Vieira said. “More research is needed to see if variation in the gene is associated with different activity profiles.”

Ayla Ozturk and Pouran Famili of the School of Dental Medicine co-authored the Journal of Dental Research paper.

Pitt co-authors of the PLoS One paper were Kathleen Deeley, Xiaojing Wang and Renato Menezes of the Department of Oral Biology and the Center for Craniofacial and Dental Genetics and Karen Cuenco of the Department of Oral Biology, the Center for Craniofacial and Dental Genetics and the Department of Human Genetics in the Graduate School of Public Health.

The second study was funded by the Pitt School of Dental Medicine and Brazilian funding agencies.

Cancer research presented

Researchers at the University of Pittsburgh Cancer Institute (UPCI) were among the presenters at the recent annual meeting of the American Association for Cancer Research.

DNA repair proteins and cancer treatment

Laura Niedernhofer, a faculty member in microbiology and molecular genetics in the School of Medicine, presented her work on the use of proteins in the DNA repair pathways as markers to predict the effectiveness of certain cancer drugs.

“The non-surgical treatment of head and neck cancers uses drugs and radiation therapy that work by causing DNA damage,” she explained. “But about half of these patients have tumors that are resistant to these therapies. That could be because some people have more repair proteins that act quickly to fix what’s broken by the treatments, allowing the cancer cells to survive.”

Niedernhofer’s team analyzed tumor samples from patients with head and neck cancers and found that those who had lower levels of a protein called XPF, which is an essential component of DNA repair pathways, tended to have better clinical outcomes than those whose XPF levels were high.

The research is supported by a Specialized Program of Research Excellence (SPORE) grant in head and neck cancer from the National Cancer Institute and the National Institute of Environmental Health Sciences.

Anti-estrogen drugs and lung cancer

Jill M. Siegfried, faculty member in pharmacology and co-director of UPCI’s lung and thoracic malignancies program, presented findings from a study that showed when compared to placebo, the aromatase inhibitor anastrazole, or Arimidex, reduced the number and size of lung tumors in mice bred to develop the cancer after exposure to a tobacco carcinogen. When fulvestrant, an anti-estrogen drug, was used in combination with anastrazole, the number of tumors decreased even more.

“Anti-estrogen drugs have been shown to be effective in preventing and treating breast tumors that carry estrogen receptors and the enzyme aromatase, which synthesizes estrogen,” Siegfried said. “We wanted to see if that held true for lung tumors with estrogen receptors and aromatase expression. Our results suggest that modifying estrogen signaling could be a beneficial approach for lung cancer treatment and prevention, as well.”

The study is supported by a SPORE grant in lung cancer, for which Siegfried is the principal investigator.

Young local workers among the nation’s best educated

A recent report in the Pittsburgh Economic Quarterly published by the University Center for Social and Urban Research (UCSUR) has found that Pittsburgh is home to the fifth most-educated young workforce in the nation.

UCSUR regional economist Chris Briem used U.S. census data to compare the educational attainment of workers aged 25-34 in Pittsburgh and 40 other metropolitan areas.

People in this age group typically have completed their education and entered the workforce, according to Briem, making the bracket a good indicator of a local workforce’s education level as well as of a region’s economic competitiveness.

This younger group also tends to have had more formal education than previous generations, particularly in cities with a history of heavy industry that provided career-long jobs without requiring advanced degrees, Briem said.

Of working Pittsburghers in this demographic, 48.1 percent have earned at least a bachelor’s degree. The national average is 34.7 percent for the same age group.

Leading the nation is Boston with 56 percent, followed by San Francisco, Washington, D.C., and Austin.

Pittsburgh tied with Washington, D.C., for the highest percentage of workers aged 25-34 who have earned a graduate or professional degree, with 21.5 percent.

Boston, ranked third, had about 19 percent.

Only 2.2 percent of Pittsburgh workers ages 25-34 did not have  a high school diploma or equivalent, the lowest percentage in the survey. At the other end of the spectrum, Houston led with 19.5 percent.

According to Briem, when the educational attainment of Pittsburgh workers as a whole is categorized by age, it provides an illustration of the city’s post-industrial transition. For the 35-44 and 45-54 age groups, the percentage of those with at least a bachelor’s degree is slightly above the national average — 39.6 percent compared with 34.6 percent for the 35-44 age group and 34.2 percent compared with 32.2 percent for the 45-54 age group.

For Pittsburgh workers aged 55-64, 31.7 percent hold at least a bachelor’s degree, lower than the national average of 36.7 percent. The gap widens for Pittsburgh workers over age 65, in which only 24.4 percent have a degree, compared to 34.5 percent nationwide.

The full article is available at www.ucsur.pitt.edu/files/peq/peq_2010-03.pdf.

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