University Times

2 profs named Sloan fellows

Two Pitt faculty members are among 118 junior professors from the United States and Canada who have been named 2009 Alfred P. Sloan Research Fellows. The Sloan fellowships are presented to young science researchers.

Brent Doiron of mathematics and Michael Grabe of biological sciences will receive two-year, $50,000 awards from the New York-based Alfred P. Sloan Foundation.

Doiron’s research focuses on the creation and study of mathematical models of neural processing.

Grabe develops computer models that help explain biological phenomena, and his Sloan fellowship research could enable a better understanding of how proteins interact with cellular membranes.

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MWRI receives $100K for cancer research

The Magee-Womens Research Institute (MWRI) will receive $100,000 from the Pennsylvania nonprofit organization A Glimmer of Hope to fund research on premenopausal breast cancer.  

In partnership with the University of Pittsburgh Cancer Institute and Magee-Womens Hospital, MWRI is involved in basic and clinical investigations to assess a full range of issues related to breast cancer and its psychosocial and behavioral impacts.  

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Colon cancer vaccine tested

Researchers at the School of Medicine have begun testing a vaccine that might be able to prevent colon cancer in people at high risk for developing the disease.

Colon cancer takes years to develop and typically starts with a polyp, a benign but abnormal growth in the intestinal lining, explained principal investigator Robert E. Schoen, professor of medicine and epidemiology. Polyps that could become cancerous are called adenomas.

People who develop advanced adenomas undergo regular surveillance with colonoscopy so that recurrent polyps, which are common, can be removed before matters get worse, Schoen said.

“Immunotherapy might be a good alternative to colonoscopy because it is noninvasive and nontoxic,” he noted. “And, it could provide long-term protection.”

Vaccines currently in use to prevent cancer work by blocking infection by viruses that are linked with cancer. However, Pitt’s vaccine is directed against an abnormal variant of a self-made cell protein called MUC1, which is altered and produced in excess in advanced adenomas and cancer.

“By stimulating an immune response against the MUC1 protein in these precancerous growths, we may be able to draw the immune system’s fire to attack and destroy the abnormal cells,” Schoen said. “That might not only prevent progression to cancer, but even polyp recurrence.”

According to co-investigator Olivera Finn, professor and chair of immunology, MUC1 vaccines have been tested for safety and immunogenicity in patients with late-stage colon cancer and pancreatic cancer.

“Patients were able to generate an immune response despite their cancer-weakened immune systems,” she noted. “Patients with advanced adenomas are otherwise healthy and so they would be expected to generate a stronger immune response. That may be able to stop precancerous lesions from transforming into malignant tumors.”

About a dozen people have received the experimental vaccine, and researchers intend to enroll another 50 or so into the study. Participants must be between 40 and 70 years old and have a history of developing adenomas that are deemed advanced.

Pitt’s colon cancer vaccine was funded by the National Cancer Institute and The Nathan S. Arenson Fund for Pancreatic Cancer Research. Its adjuvant component, which enhances the immune system’s ability to respond to the target protein, was developed and provided by Washington, D.C.-based Oncovir.

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Glowing TB detection developed

Pitt researchers have contributed to the development of an on-site method to quickly diagnose tuberculosis (TB) and expose deadly drug-resistant strains that can mingle undetected with treatable strains. The findings appeared in the March 19 edition of the online journal PLoS ONE.

The researchers engineered bacteriophages — tiny viruses that attack bacteria — to inject TB bacteria with a glowing, fluorescent-green protein.

The method must undergo clinical trials, but it has potential as a valuable, timesaving tool in rural African areas besieged by TB, explained senior author Graham Hatfull, chair and Eberly Family Professor of Biological Sciences. Hatfull conducted the research with Pitt postdoctoral fellow Mariana Piuri and William Jacobs Jr. of Albert Einstein College of Medicine, Yeshiva University.

Hatfull said, “A report from South Africa showed that the extensively drug-resistant TB strains can kill within 16 days, on average. In rural Africa, it takes too long to collect samples, send them off, do the test and have the data sent back. Clinicians need rapid, relatively cheap and simple methods for detecting TB and drug-resistant strains at the local clinic. This test provides a quick diagnosis so the patient can be isolated and treated.”

The group constructed bacteriophages specific to TB that have a green fluorescence protein (GFP) implanted in their genome. Bacteriophages spread by injecting their DNA into bacterial cells. In this case the GFP gene accompanies the DNA into the TB cell, causing the cell to glow. A clinician can detect the GFP’s glow with equipment available at many clinics.

Jacobs said, “The development of reporter flurophages allows us to bypass the existing method of diagnosing TB, which requires cultivating slow-growing bacteria in a biosafety level 3 environment, a time-consuming and costly process. By infecting live tuberculosis cells with a flurophage, a quick and highly sensitive visual reading can be done. We are optimistic that we can move the diagnostic process from several weeks to several days or even hours, which could have a significant impact on treatment.”

Besides quick diagnosis, the test also could be used to distinguish treatable TB strains from those that are drug resistant, a chore that can take months, Hatfull said.

Hatfull and his colleagues treated tuberculosis with antibiotics at the same time the bacteriophages were introduced; the TB strains that were sensitive to antibiotics died, but the drug-resistant cells survived and continued to glow.

The PLoS ONE paper is available at www.pitt.edu/news2009/Hatfull-paper.pdf.

The group’s research was funded as part of a new initiative from Howard Hughes Medical Institute, which recently announced it would partner with South Africa’s University of KwaZulu-Natal to establish an international research center focused on the TB and HIV co-epidemics in Africa.

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Prostate tests don’t cut deaths

Annual screenings for prostate cancer led to more diagnoses of the disease, but no fewer prostate cancer deaths, according to a new report from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial.

The PLCO study began in 1992 to determine whether certain cancer screening tests can help reduce deaths from prostate, lung, colorectal and ovarian cancer by enabling doctors to discover and treat the diseases earlier. Screening of participants ended in late 2006. Follow-up of participants is anticipated to continue for several more years.

Joel L. Weissfeld was principal investigator for the University of Pittsburgh Cancer Institute (UPCI) PLCO Cancer Screening Center, one of 10 sites that enrolled participants.

Results appear online and in the March 26 New England Journal of Medicine.

Of the 76,693 men in the PLCO trial, roughly half were randomly assigned to screening with annual prostate-specific antigen (PSA) tests for six rounds and digital rectal exams (DRE) for four rounds. The rest were randomly assigned to usual care, but received no recommendations on annual prostate cancer screening.

Of those men who were screened annually, 85 percent had PSA tests and 86 percent had DREs. Men in the usual-care group sometimes had these tests as well.

Men who were screened annually were referred to their usual health care provider for follow-up testing if the PSA level was greater than 4.0 nanograms per milliliter (ng/mL) or if a DRE found an abnormality.

This report includes data for all participants at seven years after they joined the trial and for 67 percent of participants at 10 years after they joined the trial. Other findings include:

•At seven years, 22 percent more prostate cancers were diagnosed in the group that participated in annual screenings (2,820 men vs. 2,322 in the usual-care group). This same pattern was observed among men who were followed for up to 10 years (with 17 percent more prostate cancers diagnosed for those screened annually).

• The vast majority of men in both groups who developed prostate cancer were diagnosed with relatively early stage disease, and the number of later-stage cases was similar in the two groups.

However, men in the usual-care group had more prostate cancers that fell into the more aggressive range. The smaller number of men in the intervention group with similarly aggressive prostate cancer eventually may lead to a mortality difference between the two groups, but data analyzed so far have not shown such a difference.

• Men in both groups who were diagnosed with prostate cancer at the same stage received similar treatments. This reflects the PLCO study design policy of not mandating specific therapies.

• At seven years, 50 deaths were attributable to prostate cancer in the screening group; 44 deaths were attributable in the usual-care group.

Through year 10, there were 92 prostate cancer deaths in the screening group and 82 in the usual-care group, a difference that was not statistically significant.

Christine Berg, NCI leader of the PLCO trial and senior author of the study, said, “The National Cancer Institute wants to understand why some prostate cancers are lethal even when found early by annual screening, and what approaches can be used to identify these more aggressive cancers when they can be effectively treated.”

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Depression, SSRIs may contribute to premature birth

Pregnant women who had untreated major depression in all three trimesters of pregnancy, as well as those who took certain antidepressants, had preterm birth rates exceeding 20 percent, according to a study by School of Medicine researchers published in the March issue of American Journal of Psychiatry.

Some 10-20 percent of women struggle with major depression during pregnancy. Selective serotonin reuptake inhibitors (SSRI) usually are the first line of treatment, but can lead to preterm births if used continuously throughout pregnancy, the findings suggest.

Katherine L. Wisner, professor of psychiatry, obstetrics, gynecology and reproductive sciences and epidemiology and director of the Women’s Behavioral HealthCARE program at Western Psychiatric Institute and Clinic, said, “Given the similarity in outcomes we found for continuous SSRI treatment and continuous depression, it is possible that underlying depressive disorder is a factor in preterm birth among women taking SSRIs.”

Women exposed to either continuous SSRI treatment, or to continuous depression with no SSRI treatment, had comparable levels of increased risk for preterm birth at 21 percent and 23 percent, respectively. However, women with no exposure to either depression or SSRI medication had lower rates of preterm births, around 6 percent.

Co-authors from the Department of Psychiatry and WPIC were Dorothy K.Y. Sit, Barbara H. Hanusa, Eydie L. Moses-Kolko, Debra L. Bogen, Diane F. Hunker, James M. Perel, Sonya Jones-Ivy and Lisa M. Bodnar.

The study was supported the National Institute of Mental Health.

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Engineering grants announced

The Department of Electrical and Computer Engineering recently announced the following grants:

• Kevin Chen has received three grants totaling more than $700,000 from the National Science Foundation and the Electro-Optic Center for research in fiber optics and nanotechnology.

• Allen Cheng has been awarded a $75,000 NSF grant for his interdisciplinary bio-implantable computing research on “Exploring Artificial Neural Networks to Develop Self-Adaptive Threat Detection Techniques for Bio-Implantable System-on-Chip.”

Cheng also has received the Cell Phone as a Platform for Healthcare Award from Microsoft Research for his interdisciplinary biomedical computing research proposal: “A Mobile Platform for Continuous Real-Time Monitoring and Automatic Detection of Cardiovascular Diseases.”

The award includes a $100,000 unrestricted fund and $50,000 for equipment.

• Alex K. Jones has been awarded an NSF grant for research in the area of compilers for high performance computing.

Jones also has been awarded a grant from The Technology Collaborative to develop a low-power reconfigurable computer and design automation tool.

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