University Times

Grants awarded to researchers

Jacqueline Dunbar-Jacob, dean of Pitt’s nursing school, has received a $480,103 grant from the National Institute of Diabetes and Digestive and Kidney Diseases. The grant will fund research to evaluate an intervention aimed at improving medication adherence in comorbid conditions.

The Pennsylvania Interest on Lawyers Trust Account Board has granted $250,000 to the law school’s Martha Mannix to support provision of legal services to indigent families, primarily through the school’s Civil Practice Clinic.

The National Institute on Aging has granted $349,224 to Chester Mathis of the Pitt medical school’s Department of Radiation, for research to develop radiopharmaceuticals for non-invasive imaging studies of amyloid deposits in the brains of Alzheimer’s disease patients.

Marcia Ontell has received a $274,115 grant from the National Institute of Arthritis and Musculoskeletal and Skin Diseases for a study, “Myogenic Factors: Muscle Maturation and Regeneration.” Researchers hope the study will provide clues as to how it may be possible to increase the regeneration of muscles.

The U.S. Department of Energy has granted $800,000 to Paul Shepard of Pitt’s physics and astronomy department for experimental particle physics research.

George Zubenko of the medical school’s psychiatry department has received a $586,327 grant from the National Institute of Mental Health for a study, “Morphologic/Neurochemical Correlates of Depression in Alzheimer’s Disease.”

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Respiratory device to be evaluated for battlefield use

Researchers from the University of Pittsburgh Medical Center are partnering with U.S. Army scientists to evaluate the merit of the experimental Hattler Respiratory Catheter for use in battlefield medicine — particularly as a possible treatment for lung injuries sustained in biochemical attacks.

Made up in part of a tightly bound fabric of microporous polypropylene hollow-fiber membranes, the catheter is inserted temporarily through a vein into the leg or neck and threaded into a major vein near the heart called the vena cava. Early tests show that it can substitute 40 percent to 60 percent of a patient’s compromised lung function.

Brack Hattler, a cardiothoracic surgeon and professor of surgery at Pitt’s School of Medicine, is Pittsburgh’s principal investigator for the two-year project, which includes close collaboration with U.S. Army scientists affiliated with the Brooke Army Medical Center in San Antonio, Texas, a major training center for combat physicians.

The project is being funded by a $2 million grant from the U.S. Department of Defense that is being shared by the University of Pittsburgh Medical Center and the U.S. Army Institute of Surgical Research at Fort Sam Houston, Texas.

“What has been developed is a new way of treating lung failure,” said Hattler, who is also director of the artificial lung program at Pitt’s McGowan Institute for Regenerative Medicine. “Working in partnership with the military, academia and industry is a very exciting prospect — especially for our team of bioengineers led by Dr. William Federspiel.”

The newest phase of research is set to run through 2003 and 2004.

“For 40 years, the only available treatment for significant lung injury has been a mechanical ventilator, which has its own risks and limitations,” Hattler said. “To work, a ventilator depends on the lining of the lungs being intact. But inhalation injury — whether the caustic agent is smoke or biochemical — damages this lining and makes the injury even more difficult to treat.”

Acute respiratory distress syndrome (ARDS) can have a mortality rate of 30 percent to 50 percent, according to Hattler.

Grants and appropriations from the U.S. Department of Defense to fund research toward the development of the Hattler Respiratory Catheter have totaled more than $7 million since 1994. Also known as the Intravenous Membrane Oxygenator, the experimental device was developed and patented by Hattler.

In the civilian population, ARDS can arise from chronic obstructive pulmonary disease, emphysema and other forms of respiratory illness.

The Hattler Respiratory Catheter is designed to support lung function for seven to 10 days during healing. The device will be manufactured and distributed by ALung Technologies Inc. of Pittsburgh.

“Research we are conducting could provide a low-tech, portable, rapid solution to these kinds of injuries,” said Hattler, adding that engineers from Pittsburgh will be temporarily assigned to the San Antonio facility during the experimental device’s preclinical testing phase.

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Cheng gets $50,000 PNC Foundation award

Tao Cheng, a renowned hematology researcher specializing in blood stem cells at the University of Pittsburgh Cancer Institute (UPCI), is the second recipient of The PNC Foundation Innovation Award to support novel research projects in cancer.

Cheng receives $50,000 for his research on the development of adult acute myeloid leukemia (AML), a disease in which cancer cells are found in the blood and bone marrow.

“We are extremely grateful to The PNC Foundation for its continued support of our research programs,” said Ronald B. Herberman, director of UPCI and the UPMC Cancer Centers. “This award enables us to expand and enhance our programs which will, in effect, help advance our knowledge of cancer.”

“PNC is committed to supporting research at UPCI and is proud to further the important research of Dr. Cheng,” said Sy Holzer, president, PNC Bank, Pittsburgh, and chairman of the UPCI Council. “As one of the nation’s leading cancer centers, UPCI continues to make significant strides in translating scientific discoveries into life-saving treatments and cures, offering hope to cancer patients.”

The PNC Foundation Innovation Award consists of a $150,000 grant to be divided over three years to fund a different individual investigator or team at UPCI each year. The award was first given in 2001 to Shi-Yuan Cheng and Xiao Xiao for their research on the use of gene therapy in treating brain cancer.

In his leukemia research, Cheng, assistant professor of radiation oncology at Pitt’s School of Medicine, focuses on defining the process by which AML develops through the examination of stem cell deregulation that occurs during the disease. Understanding how stem cells — the most basic types of cells in the body — become deregulated during AML is critical to understanding the molecular events that cause leukemia cells to proliferate.

Cheng has developed new experimental models for AML that target cyclin-dependent kinase inhibitors that are critical to maintaining the stem cells. The goal of Cheng’s research is to define the facilitating roles of cyclin-dependent kinase inhibitors in the development of a subtype of AML, called M2, to better understand and treat the disease and to apply this knowledge to research in other forms of leukemia.

Cheng was recruited to UPCI in summer 2001 from the Harvard Medical School. He has received numerous awards for his work on stem cell biology and recently received the American Society of Hematology Scholar Award.

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Research looks at possible genetic differences in susceptibility to Alzheimer’s

Pitt’s Graduate School of Public Health (GSPH) and Alzheimer’s Disease Research Center (ADRC) have received a National Institutes of Health grant that may allow researchers to determine whether there are genetic differences in people’s susceptibility to Alzheimer’s disease (AD).

The $807,000 grant will fund continuation of an existing study that is examining how several genes and their mutations may affect the risk of late-onset (60 years or older) AD.

“In this larger, case-control study, we will evaluate the link between these mutations and the risk of AD to determine whether there is indeed a genetically specific predisposition to AD,” said principal investigator M. Ilyas Kamboh, professor of human genetics and psychiatry at GSPH.

Co-principal investigator Steven T. DeKosky, Pitt’s ARDC director and neurology department chairperson, added: “In this next phase of our research, we also hope to localize susceptibility genes in the critical regions of the brain that are important for memory.”

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Early lead exposure may be cause of juvenile delinquency

Children exposed to lead have significantly greater odds of developing delinquent behavior, according to a Pitt researcher.

Results of the study, directed by Herbert Needleman, professor of child psychiatry and pediatrics, were published Jan. 6 in the journal Neurotoxicology and Terotology.

Needleman, known for his groundbreaking studies on the effects of lead exposure on children that were instrumental in establishing nationwide government bans on lead from paint, gasoline and food and beverage cans, examined 194 youths convicted in the Juvenile Court of Allegheny County, and 146 non-delinquent controls from high schools in Pittsburgh.

Bone lead levels, measured by K X-ray fluorescence spectroscopy of the tibia, showed that the delinquent youths had significantly higher mean concentrations of lead in their bones — 11.0 parts per million (ppm) — compared to 1.5 ppm in the control group.

“This study provides further evidence that delinquent behavior can be caused, in part, by childhood exposure to lead,” Needleman said. “For years, parents have been telling their pediatricians that their children’s behavior changed after they were lead poisoned, and the children became irritable, overactive and aggressive. These results should be a call to action for legislators to protect our children by requiring landlords to not simply disclose known instances of lead paint in their properties, but to remove it.”

While this study is the first to show that lead exposure is higher in convicted delinquents, it is part of a growing body of evidence linking lead to cognitive and behavioral problems in children.

In 1996, Needleman published a study of 300 boys in Pittsburgh public schools and found that those with relatively high levels of lead in their bones were more likely to engage in antisocial activities like bullying, vandalism, truancy and shoplifting. In 1979, Needleman, using measurements of lead in children’s teeth, concluded that children with high lead levels in their teeth, but no outward signs of lead poisoning, had lower IQ scores, shorter attention spans and poorer language skills.

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Study to assess power needsof satellites, unpiloted drones

Replacing a power source in a satellite or an unpiloted drone vehicle is extremely difficult, so Pitt researchers are working with colleagues at IBM Corp. to study power management in such machines.

As part of the research, IBM has donated $70,000 worth of specialized equipment to Pitt for the project, Power Management in Reliable and Highly Available Systems.

“Highly available computer systems are designed to function despite some component failure,” said principal investigator Rami Melhem, professor and chair of Pitt’s Department of Computer Science and professor in the electrical engineering and computer engineering departments. “These systems are designed to tolerate failure and even to repair themselves such that the users do not feel any disruption of service.”

Daniel Mossé, associate professor in the Department of Computer Science, is collaborating on the project.

The equipment, which is being made available through IBM’s Sponsored University Research program, falls into three categories:

• Systems built around variable speed central processing units;

• Disk arrays to study power management issues in storage structures, and

• High-end servers to allow large simulations to evaluate the tradeoffs in the systems studied in the project.

“Power management is important in three cases,” Melhem said. “It is important for portable devices where battery life is limited; for remotely deployed systems, such as satellites and autonomous vehicles, where energy is a scarce resource; and for large computer centers where power consumption and cooling costs become major factors from an economic and an environmental point of view.”

The research is part of two ongoing collaborations between Pitt’s Department of Computer Science and IBM on projects for the Defense Advanced Research Projects Agency.

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Pitt researcher awarded $1.6 million for study of disrupted brain development

Scientists suspect that schizophrenia has its roots in early fetal brain development, and a Pitt researcher will explore that theory using a $1.6 million grant from the National Institute of Mental Health, one of the National Institutes of Health.

“Even though the psychosis is not expressed until adulthood, there is evidence that schizophrenia is a disorder whose pathology begins early in development. There is further evidence that developmental problems during the second trimester of humans can increase the incidence of schizophrenic births,” said Anthony Grace, a professor of neuroscience and psychiatry at Pitt and the study’s primary investigator.

Grace will use animal studies to examine the way the section of the brain called the nucleus accumbens, which regulates motivation and reward, interacts with other parts of the brain.

“The nucleus accumbens is a region in the brain where antipsychotic drugs are thought to act and which likely has a major role in the development of schizophrenia,” Grace said. “In this study, I will be examining the basic physiology of how higher level systems interact with the accumbens through changes in the brain’s chemistry, especially the dopamine system, and the brain’s circuitry.”

While the emphasis for Grace’s five-year study will be on schizophrenia, he said that the biological principles he will be examining are likely to be applicable to other psychiatric disorders.

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Angiogenic gene therapy studied for coronary artery disease

Clinicians at the University of Pittsburgh Medical Center’s (UPMC) Cardiovascular Institute have begun a Phase IIb/III clinical research study of angiogenic gene therapy for patients with stable exertional angina due to coronary artery disease. The study will assess whether gene transfer can be safely administered and whether it can stimulate the growth of new blood vessels in the heart and benefit participants with angina.

The randomized, double blind, placebo-controlled study will evaluate the efficacy of a protein known as fibroblast growth factor, Ad5FGF-4, versus placebo.

Angina is chest pain that results when the heart does not receive enough blood.

Researchers are studying angiogenic gene therapy as a potential option to stimulate angiogenesis, an important natural process in the body, by supplementing the heart with angiogenic growth factor protein. This may help provide alternate routes for oxygenated blood to flow around narrow or blocked arteries due to atherosclerosis.

“Angiogenic gene therapy with Ad5FGF-4 is an innovative approach that could potentially transform how coronary artery disease is managed,” said Joon S. Lee, assistant professor of medicine at Pitt’s School of Medicine, director of Interventional Cardiology, associate director of Cardiac Catheterization Laboratories and principal investigator in the Pittsburgh arm of the study.

UPMC is among an estimated 100 centers nationwide participating in the trial. A total of 450 participants will be enrolled nationwide with about 15 enrolled at UPMC. Participants will range in age from 30-75 years.

Call 412/647-6136 for more information about eligibility.