Research News

Study points to new uses, unexpected side effects of already-existing drugs

estaples — 2009-11-04T15:37:29Z

Scientists at the University of North Carolina at Chapel Hill School of Medicine and the University of California, San Francisco have developed and experimentally tested a technique to predict new target diseases for existing drugs.

The researchers developed a computational method that compares how similar the structures of all known drugs are to the naturally occurring binding partners -- known as ligands -- of disease targets within the cell. In a study published this week in Nature, the scientists showed that the method predicts potential new uses as well as unexpected side effects of approved drugs.

“This approach uncovered interactions between drugs and targets that we never could have predicted simply by looking at the chemical structures,” said senior study author Bryan Roth, M.D., Ph.D., professor of pharmacology and director of the National Institute of Mental Health Psychoactive Drug Screening Program at UNC. “We may now have a way to predict what side effects are likely to occur from treatment before we even put a drug into clinical testing.” Roth is also a member of the UNC Lineberger Comprehensive Cancer Center.

Many of the most successful drugs on the market today are being prescribed for ailments that are quite different from the ones they were originally designed to treat. Viagra, for instance, was once intended for coronary heart disease but now is used to combat erectile dysfunction. The discovery of surprising uses of developed drugs can sometimes be the result of serendipity, as unforeseen side effects emerge from clinical trials. In the past, researchers have tried to predict drug interactions by looking for chemical similarities among the possible targets of pharmaceutical compounds.

However, some drug targets which look very similar to one another bind very different ligands, and some targets that don't have any obvious similarity bind similar ligands, says Brian Shoichet, Ph.D., co-senior study author and professor of pharmaceutical chemistry at UCSF. “So if instead we were to organize targets by the ligands they recognize, it could reveal different patterns than traditional approaches, and illuminate new opportunities for drugs to bind to unexpected targets.”

A team of researchers led by Roth and Shoichet did just that, comparing the structures of 3,365 FDA-approved and investigational drugs against the structures of hundreds of targets, defining each target by its ligands. They then honed in on thirty of the strongest predictions, validating the actual physical interactions between the drugs and targets in wet laboratory experiments.

In one of their follow-up experiments, the scientists investigated the molecular targets of the hallucinogenic substance dimethyltrytamine (DMT), which had previously been postulated to act through a site known as the sigma-1 receptor. Using the computational approach, Roth and colleagues found that DMT had a high affinity for serotonin receptors, including the binding site for LSD, another hallucinogen.

They also showed that the substance is hallucinogenic in normal mouse models but not in ones lacking the serotonin receptor. Roth says the power of their approach is it can be used to uncover the real targets of pharmaceutical compounds quickly and efficiently, and will probably lead to a greater understanding of the many molecular targets of each drug.

“Drugs are not as selective as we once thought,” said Roth, who is also a professor in the School of Pharmacy’s medicinal chemistry and natural products division. “It turns out that the most non-selective drugs are frequently the most effective for complex diseases. Rather than ‘magic bullets,’ we need to come up with ‘magic shotguns’ that hit more than one molecular target at a time. We could use this computational approach to identify the drugs that hit the right targets and miss the wrong ones.”

Study co-authors from UNC include Vincent Setola, research associate professor; Atheir Abbas, former graduate student; Sandra J. Hufeisen, senior research assistant; Niels H. Jensen, research associate; Michael B. Kuijer, research technician; Roberto C. Matos, research technician; Thuy B. Tran, research technician; Ryan Whaley, research technician; and Richard A. Glennon. The paper’s first author is Dr. Michael Keiser, from the UCSF side of the collaboration. Also from UCSF were Drs. John Irwin, Christian Laggner and Jerome Hert, and PharmDs Kelan Thomas and Douglas Edwards.

Funding for the studies at UNC and at UCSF came from the National Institutes of Health.

Media contact: Les Lang, (919) 966-9366, llang@unch.unc.edu

[top]

Breast Cancer Research Foundation funds four at UNC Lineberger

ccondrey — 2009-11-05T20:52:27Z

CHAPEL HILL, NC – Four faculty members from UNC Lineberger Comprehensive Cancer Center have been awarded yearlong grants from the Breast Cancer Research Foundation (BCRF).

Dr. Lisa Carey, medical director of the UNC Breast Center and associate professor of medicine; Dr. H. Shelton Earp, Lineberger professor and director of the UNC Lineberger Comprehensive Cancer Center; Dr. Hyman Muss, director of geriatric oncology at UNC Lineberger and professor of medicine and Dr. Charles Perou, associate professor of genetics and pathology. Each received a one-year grant designed to further promising research in the field of breast cancer.

“We are proud to be one of only a handful of university cancer centers to receive four grants from BCRF this year. The foundation and the generous people and organizations who support their research programs expect the highest degree of scientific merit and we are pleased to be well-represented in this elite group,” said Earp.

BCRF is supporting a clinical trial led by Dr. Carey, designed to understand which women benefit most and are harmed the least by chemotherapy. Carey and her colleagues are collecting genetic material from 1,000 breast cancer patients and 1,000 healthy women of similar age, race, and ethnicity before breast cancer patients are treated with chemotherapy, allowing researchers to directly measure responsiveness of their breast cancer to chemotherapy that is given. By comparing the genetic profiles in those patients who respond to chemotherapy with those who do not, the team can validate which genetic mutations are associated with differences in treatment outcomes.

Dr. Earp’s team will continue a three-part research program focused on developing a new and Improved Anti-HER2 Breast Cancer Vaccine; understanding the genetic determinants of breast cancer’s development and response to therapy; and examining the EGF Receptor family in breast cancer and the role of HER4.

The first project performed with Dr. Jon Serody is a therapeutic cancer vaccine clinical trial that combines two drugs with the vaccine in the treatment of women with high HER2-expressing metastatic breast cancer. The second project has worked with more than 1,000 women to obtain DNA samples as well as epidemiologic, clinical, therapeutic and outcome data so that researchers can better understand how complex genetic inheritance influences a woman’s predisposition to breast cancer. Finally, the researchers are studying another member of the EGF/HER2 receptor family, HER4. One variant of HER4 slows breast cancer cell growth, while the other actually stimulates growth. The team hopes to unravel the mechanisms by which those two variants, which differ by only one percent of the gene’s length, have opposite effects on breast cancer cell growth.

Dr. Muss’ new project focuses on patients aged 65 and older, assessing the costs and benefits of adjuvant chemotherapy. While this therapy has been shown to improve survival in older women with breast cancer, side effects may interfere with the quality of life and daily function. In collaboration with UNC Lineberger colleague Dr. Ned Sharpless, Muss’ team is seeking to understand the effect of adjuvant chemotherapy on a biomarker of aging called p16INKa. They will also measure the biomarker in patients treated only with surgery and those treated with adjuvant endocrine therapy to determine if the increased expression of this biomarker in some older patients is associated with their susceptibility to the age-promoting effects and associated toxicities of chemotherapy.

Dr. Perou’s team is focused on two subtypes of breast cancer that are associated with poor clinical outcomes, “Luminal B” and “Claudin-low.” The team is focused on identifying how genetic alterations cause these tumors and determining the role of stem cells in their biology. Using the genomic data for these tumor types and key clinical data, Perou’s team is building a predictive mathematical model for breast cancer patient outcomes that could assist doctors in making therapeutic decisions.
About BCRF

The Breast Cancer Research Foundation is an independent 501 (c) (3) not-for-profit organization whose mission is to achieve prevention and a cure for breast cancer in our lifetime by providing critical funding for innovative clinical and translational research at leading medical centers worldwide, and increasing public awareness about good breast health. More information is available at www.bcrfcure.org.

Contact: Ellen de Graffenreid, (919) 962-3405, edegraff@med.unc.edu

Clinical trial promotes new standards for colorectal cancer treatment

ccondrey — 2009-11-05T20:52:28Z

CHAPEL HILL, NC – In a review article published this month in The Oncologist, UNC’s Dr. Richard M. Goldberg and a team of colleagues catalogue how the data collected in a single large comparative clinical trial testing combination chemotherapy for metastatic colorectal cancer has been used not only to benefit the patients that enrolled but also patients who subsequently developed the disease.

It has also helped to refine the clinical trials process and move forward the potential for individualized therapy for patients. These benefits of this collaboration between patients, physicians across the U.S. and Canada, the National Cancer Institutes of the U.S. and Canada, and two pharmaceutical companies (Pharmacia and sanofi-aventis) are being still being realized five years after the original trial concluded.

Not only did the Phase III trial, which ran from 1997-2004, prove that combination chemotherapies adding new drugs to the standard treatment in use for 50 years are effective in treating metastatic colorectal cancer, but it also provided data for more than 25 additional scientific papers. This ongoing research has helped to improve the prognosis and change the standard of care for patients with this diagnosis.

“The history of this study shows how patients’ decisions to enroll in clinical trials can benefit thousands of others, even years down the road,” said Goldberg, who is Physician-in-Chief of the N.C. Cancer Hospital and Associate Director for Clinical Research at UNC Lineberger Comprehensive Cancer Center.

“These individuals have helped doctors and scientists change the way we treat metastatic colorectal cancer and simplify the way we run clinical trials in cancer patients.” Based on the trial the US Food and Drug Administration approved a new agent, oxaliplatin, administered with 5-fluorouracil for the indication "treatment of previously untreated patients with colorectal cancer that had spread to other organs" in 2004.

As one of the first clinical trials to monitor chemotherapy toxicity in real-time, the study allowed researchers to quickly eliminate drug combinations that were more likely to result in negative outcomes for patients. Over the course of the study, as the field of pharmacogenetics evolved, researchers were able to use the individual patients' DNA collected with a simple blood test to better pinpoint which were most likely to have severe side effects. The DNA analysis also helps doctors determine which patients derive greater benefits from a particular drug and adjust their chemotherapy to minimize risk, while maximizing the chances that their cancer would respond to therapy.

“Over time, the fact that this study collected DNA and plasma with patient permission has been important to our ability to make significant progress in understanding how patients’ genetic profiles interact with anti-cancer drugs,” said Goldberg.

Data from the study was also used to examine how patients did with a combination of surgery and drug therapy, to study how the combination drug therapy worked in patients with different risk profiles based on the type and progression of their cancer, and to assess the economic cost-benefit of combination therapies.

"The original data collected has also been combined with data from other clinical trials to examine overall survival rates and to explore differences in outcomes based on patient age and symptom profiles so that we could understand the risks and benefits when we treat older and sicker patients with the more intensive treatments" Goldberg said. "The data was also used to simplify how we follow tumor measurements and side effect profiles in clinical trials speeding the pace and reducing the cost of research."

“The history of this study demonstrates how sharing data among groups of scientists and doctors and asking questions that span scientific disciplines can help us make progress that is meaningful for patients over the relatively short time frame of approximately a decade,” he added.

Other investigators on the review study were Hanna Sanoff, MD, clinical assistant professor of medicine and Howard McLeod, PharmD, professor of pharmacy and UNC Lineberger member, Daniel J. Sargent, PhD, Erin Green and Jan Buckner, MD from the Mayo School of Medicine in Rochester, Minnesota, and Roscoe Morton, MD from the Iowa Oncology Research Association CCOP.

The original clinical trial was a partnership between the enrolled patients, the National Cancer Institutes of the US and Canada, NCI sponsored cooperative groups, industry, and investigators at academic centers, Community Clinical Oncology Programs and private practices. The review study was supported by the North Central Cancer Treatment Group (NCCTG) and NCCTG Biospecimen Resource, sanofi-aventis and Pharmacia.

Contact: Ellen de Graffenreid, 919-962-3405, edegraff@med.unc.edu

Messenger RNA with FLASH

ccondrey — 2009-11-05T20:52:28Z

CHAPEL HILL -- A study from the University of North Carolina at Chapel Hill has identified a key player in a molecular process essential for DNA replication within cells.

The new findings highlight a protein called FLASH, already shown to play a role in initiating apoptosis, or programmed cell death. Apoptosis is a normal biochemical response that occurs when a cell is damaged beyond repair after viral infection or accumulation of mutations that could lead to uncontrolled cellular proliferation, or cancer. Apoptosis is also crucial to the developing embryo through selective cell death, which allows proper differentiation of physical structures, such as fingers and toes.

According to senior study author Zbigniew Dominski, Ph.D., associate professor of biochemistry and biophysics at UNC, the new study demonstrates that FLASH is also required for the proper synthesis of histone messenger RNA, which gives rise to histone proteins.

Histones are the chief protein components of chromatin and act as a scaffold allowing packaging of DNA into a condensed form that fits inside the nucleus of a cell. As the DNA interacts with histones and with metabolic signals from within the cell, these proteins help regulate gene expression.

“Our study suggests for the first time that a potential link exists between the processes of histone messenger RNA formation and apoptosis,” Dominski said. “FLASH is crucial for the production of histone messenger RNA, without which the cell can’t make the histone proteins around which DNA is packaged.”

The research is described in the Oct. 23, 2009 issue of the journal Molecular Cell.

For the study, Dominski adapted a laboratory system that reproduces in the test tube what normally occurs in the cell when FLASH participates in the biochemical cleavage event that results in mature histone messenger RNA. This enabled his team to explore what might occur when FLASH was added or removed.

“We could then figure out exactly what portion of FLASH would restore the protein’s function in generating histone mRNAs and remarkably, only the first 100 or so amino acids are required. The remaining 2,000 amino acids of this large protein likely control other processes in the cell, including apoptosis and DNA replication,” he explained.

Co-author William F. Marzluff, Ph.D., is distinguished professor of biochemistry and biophysics and executive associate dean for basic research in the UNC School of Medicine. He noted that FLASH is the first component found in this protein complex “that integrates or initiates many cellular functions – DNA replication, apoptosis, histone production. Having this small piece of the puzzle makes it a lot easier to identify others.”

Other UNC coauthors include Xiao-cui Yang, laboratory technician, and Yan Yan, undergraduate student, both from the Department of Biochemistry and Biophysics and the UNC Program in Molecular Biology and Biotechnology and Brandon D. Burch, graduate student in in genetics and molecular biology.

Funding for the study came from the National Institute of General and Medical Sciences, a component of the National Institutes of Health.

Moderate weight loss helps reduce risk of osteoarthritis in the knee

ccondrey — 2009-11-05T20:52:28Z

CHAPEL HILL, N.C. – Here’s another good reason to lose even a moderate amount of weight: it could reduce your risk of developing osteoarthritis in your knees.

People who are overweight and lose just 5 percent of their weight are less likely to develop osteoarthritis of the knee, or knee OA, compared to people who gain weight, according to data from a large ongoing study by the Thurston Arthritis Research Center at the University of North Carolina at Chapel Hill School of Medicine.

“We hear a lot of messages about how obesity affects cardiovascular disease and diabetes, but arthritis is often overlooked,” says Lauren Abbate, a third-year medical student at UNC and lead investigator of the knee OA paper, presented Monday, Oct. 19, 2009, at the American College of Rheumatology scientific meeting in Philadelphia.

“OA is painful and debilitating. Effective treatments are limited and there’s not a cure. But if we can get people to lose weight we may reduce their risk and reduce the pain and disability associated with this condition,” Abbate says.

More than 27 million Americans have OA, the most common joint disease affecting middle-aged and older people. OA causes progressive damage to the joint cartilage and changes in the structures around the joint, which can include fluid accumulation, bony overgrowth and loosening and weakness of muscles and tendons, all of which may limit movement and cause pain and swelling.

Abbate and her colleagues used data from the Johnston County Osteoarthritis Project, one of the largest ongoing population-based studies of arthritis in the world. It began at Thurston in 1990 and is funded by the Centers for Disease Control and Prevention and the National Institutes of Health.

The researchers included 1,480 men and women 45 and older who were disease-free in at least one knee and followed them for approximately six years to see who developed radiographic OA – disease confirmed by X-rays; almost two-thirds were women, and more than 25 percent were African Americans.

They then divided people into categories based on weight change: people who lost 5 percent or more of their total body weight, people who maintained within 3 percent above or below their weight and those who gained at least 5 percent more than their weight.

“It was our hope that people who maintained weight would have reduced risk, but obesity is such a strong risk factor for OA, that maintaining weight showed no significant benefit,” says Abbate, who recently finished her doctoral degree in epidemiology from the UNC Gillings School of Global Public Health. She also has a master’s of science in public health from the school.

Weight loss can be difficult to achieve. But, Abbate says, people can aim for losing a certain percentage of their weight instead of shooting for an ideal number. “For someone who weighs 200 pounds, losing 5 percent just means losing 10 pounds,” she says.

Abbate’s paper was one of several research highlights at the ACR meeting for UNC’s Thurston Arthritis Research Center. Abbate and two other UNC medical students, Joshua Knight, a second-year student, and Shelby Addison, a third-year student, won research awards. Amanda Nelson, M.D., a fellow at Thurston, won a fellowship award.

“We have placed a high priority on working with medical and graduate students and being open to collaborating,” says Joanne Jordan, M.D., the center director and Herman and Louise Smith Distinguished Professor of Medicine at UNC’s School of Medicine. Jordan received the ACR’s Award of Distinction for Excellence in Investigative Mentoring.

“We take our role as the arthritis research center for the people of North Carolina very seriously,” Jordan said. “That is why we are always looking for ways to bring our research findings to the community and to learn from the community.”

Media contact: Clinton Colmenares, (919) 966-8757 or ccolmena@unch.unc.edu

Scientists demonstrate link between genetic defect and brain changes in schizophrenia

ccondrey — 2009-11-05T20:52:29Z

CHAPEL HILL – For decades, scientists have thought the faulty neural wiring that predisposes individuals to behavioral disorders like autism and psychiatric diseases like schizophrenia must occur during development. Even so, no one has ever shown that a risk gene for the disease actually disrupts brain development.

Now, researchers at the University of North Carolina at Chapel Hill School of Medicine have found that the 22q11 gene deletion – a mutation that confers the highest known genetic risk for schizophrenia – is associated with changes in the development of the brain that ultimately affect how its circuit elements are assembled.

In studies conducted in mice, the researchers discovered that the genetic lesion alters the number of a critical subset of neurons that end up in the brain’s cerebral cortex – the region critical to reasoning and memory. The defect also causes another type of nerve cell – called GABAergic neurons – to be misplaced within the brain’s cortical layers, resulting in a subtle miswiring of the organ.

“For practically ever other disease, we know what cells take a hit,” said senior study author Anthony LaMantia, Ph.D., professor of cell and molecular physiology and co-director of the Silvio M. Conte Center for Research in Mental Disorders at the UNC School of Medicine. “For multiple sclerosis the myelinating oligodendrocytes in the brain falter, for Lou Gehrig’s disease the motor neurons in the brain stem degenerate. But we really had no idea what was happening in schizophrenia, or in any of the psychiatric diseases for that matter – until now.”

His study will be presented Oct. 17 at the Society for Neuroscience meeting in Chicago, by Daniel Meechan, Ph.D., post-doctoral fellow in the LaMantia laboratory and the first author of a recent paper in Proceedings of the National Academy of Sciences that details the findings.

The study lends the first clear support to the “neurodevelopmental hypothesis” – a scientific theory LaMantia calls the “Hail Mary” of schizophrenia pathologists.

For many years, researchers searched in vain for any indication that the brains of patients with schizophrenia were different from normal subjects --for some laboratory finding along the lines of the plaques and tangles characteristic of Alzheimer’s disease or the degeneration of dopamine cells that are the calling card of Parkinson’s disease. Similar degenerative change has never been identified for schizophrenia. Finally they proposed that the defects in schizophrenia must arise before the brain is fully formed, rather than after.

Then researchers began to discover regions of the genome -- many of which had neurodevelopmental functions -- that made people susceptible to schizophrenia.

In this study, LaMantia and his colleagues decided to pursue deletion of one such region on human chromosome 22, which causes DiGeorge syndrome in humans, because it is the single best-defined genetic lesion associated with schizophrenia. They tracked two subclasses of neural stem cells -- called basal and apical progenitors -- throughout early brain development in a mutant mouse with the same genetic deletion. They found that the basal progenitors divided more slowly than they should, and as a result the cells that they give rise to in the cortex were not generated in the proper numbers.

The researchers also looked at another population of cells, the GABAergic cells that are thought to essentially put the brakes on electrical activity in mature cortical circuits. The function of these cells is believed to be one of last processes to be disrupted in the schizophrenic brain. LaMantia found that these GABAergic neurons never made their way to their correct positions in the cortical layers of the brain of the mouse model of DiGeorge Syndrome .

The researchers would now like to figure out how these alterations in the circuitry of the brain affect the behavior of the mouse. They also hope that understanding the “mis-wiring” of the brain in a genetic animal model of schizophrenia would help them understand the causes of the disease in the general population.

“Now that we know what cells can be affected in schizophrenia, it opens up new avenues in thinking about the molecular mechanisms underlying this and other psychiatric illnesses,” said LaMantia. “We can even begin to look for biomarkers of the disease that can be used for better diagnosis and treatment.”

Funding for the studies led at UNC came from the National Institutes of Health and the Silvio M. Conte Center. Study co-authors from LaMantia’s laboratory at UNC include postdoctoral fellows Daniel W. Meechan, Erin S. Tucker and Thomas M. Maynard.

Media contact: Les Lang, (919) 966-9366, llang@med.unc.edu

Coach Williams Raises $1 Million For Cancer Research

estaples — 2009-11-05T21:17:37Z

Friday, October 16, 2009 — In just five years, Coach Roy Williams has raised more than $1 million for cancer research, treatment and prevention programs in our community. These funds have been raised through Coach Williams’ highly successful Fast Break Against Cancer event, which was launched in 2004. Coach Williams also directed half of the proceeds from the sold-out UNC Alumni Basketball game to support cancer research at UNC Lineberger Comprehensive Cancer Center.

Coach Williams Raises $1 Million For Cancer Research

estaples — 2009-11-05T20:52:29Z

Coach Williams was recognized for this significant milestone by UNC Lineberger director Dr. Shelley Earp at this year’s Fast Break Against Cancer. “Like our Tar Heels on the court, the researchers, doctors and caregivers at UNC Lineberger and the N.C. Cancer Hospital never stop fighting. We are touched and grateful for the outstanding support from Coach Williams for our efforts to bring the very best in cancer research, prevention and treatment to North Carolina and the world,” said UNC Lineberger director Dr. Shelley Earp.

Today’s breakfast celebrated the UNC Men’s Basketball 2009 NCAA National Championship and the opening of the N.C. Cancer Hospital. More than 300 guests heard personal reflections on the toll cancer takes in people’s lives by former UNC basketball player, member of the 1993 NCAA National Championship team and former NBA star Eric Montross. UNC Men’s Basketball assistant coaches, coaching great Bill Guthridge and “voice of the Tar Heels,” Woody Durham also participated.

Bidding was lively for one-of-a-kind live auction items including a pair of shoes signed by UNC All-American and National Championship MVP Tyler Hansbrough (now playing for the Indiana Pacers), one of only 75 UNC basketballs autographed by all of the members of the 2008-2009 NCAA National Championship basketball team and coaches and a package for one person to attend a pre-game locker room team meeting, watch the game from the UNC bench and attend Coach Williams’ post game press conference. Coach Williams also presented surprise auction items for bid to attendees – two unique UNC basketballs signed by all of the living members of the Naismith Memorial Basketball Hall of Fame.

Event sponsors include Atlantic Packaging ($25,000), GlaxoSmithKline ($15,000), AT&T, BlueCross BlueShield of North Carolina, The Carolina Inn, Curtis Media Group, Dixie Asset Management, Grady-White and Long Beverage, Inc. (all $10,000).

Contact: Ellen de Graffenreid, (919) 962-3405, edegraff@med.unc.edu; Dianne Shaw, (919) 966-7834, dgs@med.unc.edu

[top]

UNC scientists win $1.6 million stimulus award to accelerate decoding of human genome

estaples — 2009-11-05T20:52:29Z

Ever since the first genome sequence was published in 2001, scientists have been working to figure out what the sequence means. An analogy is walking across a desert and finding a large book in a language you don't know, then trying to figure out what the book is saying.

“In the case of the human genome, the book is a blueprint to building cells—and ultimately—the whole human. But we don't yet understand its language,” said Morgan Giddings, Ph.D., associate professor of microbiology and immunology and of biomedical engineering at the University of North Carolina at Chapel Hill.

Giddings and UNC colleague Xian Chen, Ph.D., associate professor of biochemistry and biophysics, have been developing methods for decoding the human blueprint by studying the things the blueprint produces: proteins. They relate the proteins back to the blueprint itself, to further decode the language of the genome blueprint.

Giddings and Chen have been awarded a $1.6 million 2-year “Grand Opportunities” (GO) grant from the National Human Genome Research Institute to accelerate this research. Their effort will be part of a consortium of investigators studying the human genome blueprint, titled the “ENCyclopedia Of DNA Elements” (ENCODE). The consortium’s overall goal is to assemble a comprehensive catalog of functional elements in the human genome.

With their GO grant, Giddings and Chen will generate, analyze, and release to the public large-scale data sets that allow linking of the protein products in cells to their genomic blueprints. According to Giddings, “this will significantly promote our understanding of the language of the human genome, enhancing efforts to solve pressing human health issues like heart disease and cancer by understanding how errors in the blueprint lead to disease, and how we might fix those errors.”

Giddings is a member of the Carolina Center for Genome Sciences, and Chen is technology development director for the UNC Proteomics Core. The new grant will bring 4-6 new high-tech jobs to the Triangle.

NHGRI has awarded approximately $22 million of American Recovery and Reinvestment Act 2009 funds to support research aimed at identifying and understanding the genome’s functional elements.

Media contact: Les Lang, (919) 966-9366 or llang@med.unc.edu

[top]

UNC researcher awarded grant for anti-diarrhea vaccine study in Nicaragua

estaples — 2009-11-05T20:52:29Z

A University of North Carolina at Chapel Hill researcher has been awarded a four-year, $507,000 grant from the National Institutes of Health’s Fogarty International Center to study the effectiveness of rotavirus vaccines in the Central American nation of Nicaragua.

The grant was awarded to Sylvia Becker-Dreps, M.D., M.P.H., an assistant professor of family medicine in the UNC School of Medicine, who recently completed a National Research Service Award (NRSA) Primary Care Research Fellowship at UNC. It adds to initiatives within the UNC Center for Latino Health and the UNC Institute for Global Health & Infectious Diseases’ program in Nicaragua.

“Nicaragua was one of the first developing world nations to start universal immunization of its children against rotavirus, so the lessons learned here could be important to other developing nations,” Becker-Dreps said.

Rotaviruses are the most common infectious cause of diarrhea and cause the deaths of about 527,000 children worldwide each year. “These deaths are really the tip of the iceberg- many children have repeated diarrhea episodes and end up with malnutrition, stunted growth, and even developmental delays.”

In Nicaragua, diarrhea is the leading cause of death in children between infancy and age 5. In 2006, Nicaragua implemented universal infant rotavirus immunization with the pentavalent rotavirus vaccine, which manufactured by Merck. All Nicaraguan infants receive this live, oral vaccine at the ages of 2 months, 4 months and 6 months, as do children in the United States.

Clinical trials in the U.S. and Europe have shown the vaccine to be highly effective in reducing rotavirus diarrhea, but it is not known how well the vaccine works in developing countries like Nicaragua or in preventing less severe cases of diarrhea that may never receive care in the hospital.

Becker-Dreps’ study aims to determine the effectiveness of the vaccine in the primary care setting and in the community setting in Nicaragua. In addition, researchers will perform genotyping of rotavirus-positive samples collected in the study in order to identify if shifts in rotavirus strains are occurring as a result of the immunization program.

Media contact: Tom Hughes, (919) 966-6047, tahughes@med.unc.edu

[top]