National Center for Research Resources, National Institutes of Health
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Download Entire Issue (PDF): 1.5MB Spring 2007  •  Vol. XXXI, No. 2

Contents

Message

  • Cover Story

Critical Connections

CTSA Quick Takes

Resource Briefs

Science Advances

News from NCRR

Cover Story

Critical Connections

Connecting Universities to Rural Clinics

On the other side of the country, the IDeA program in West Virginia is also enabling critical connections among different institutions and facilities and between mentors and students. Along narrow roads, nestled among the tall peaks of the Appalachian Mountains, the Tug River Health Association has, for many years, been providing health care to residents of the coalfields of southern West Virginia. The small rural clinic, a three-hour drive south of the state’s capital, is also participating in a major research effort to identify the genetic underpinnings of heart disease.

The NCRR-funded Appalachian Cardiovascular Research Network project “is a unique research collaboration that includes major research universities, undergraduate institutions, major hospitals, and rural clinics,” says Gary Rankin, the grant’s principal investigator at Marshall University, located in Huntington. “And it involves all kinds of individuals, from students to molecular biologists to clinicians.” It focuses on heart disease, a health problem that is highly relevant to West Virginians. According to statistics released by the U.S. Centers for Disease Control and Prevention in February 2007, the West Virginia population has a high prevalence of obesity, diabetes, and smoking-related illnesses. In fact, the state has the highest proportion of people with heart disease in the nation.

Although heart disease is caused by a mix of genetic and environmental factors, knowing which genes make it more likely for a person to develop the condition could help identify at-risk individuals. “We want to understand a person’s susceptibility to disease long before it develops,” says Donald Primerano, a professor at Marshall University and the program’s director. “These individuals could be advised, for example, on what diet could be beneficial to them.”

Those who are eligible to participate in the study have abnormal levels of fats, or lipids, in their blood. “To find out if they want to participate, we either call them or ask them during a regular visit to their physician,” says Primerano. Patients are recruited at three major centers (Marshall University, West Virginia University, and Charleston Area Medical Center), as well as from three small rural clinics spread out across the state, extending the program’s reach.

The research effort has already had some success in identifying genes involved in obesity-associated cardiovascular disease. For that study, researchers analyzed the sequence of DNA nucleotides within several genes already known to predispose people to heart disease and compared the sequences in overweight and obese individuals to those in normal-weight individuals.They found three genes that differ between the two groups and thus may play a role in obesity-associated cardiovascular disease. An abstract describing the work was presented at the annual meeting of the American Society for Human Genetics held last October in New Orleans.

Two more ambitious projects are now under way. Researchers are trying to identify variations in genes involved in two common conditions leading to heart disease that seem to run in families: familial combined hyperlipidemia and familial hypertriglyceridemia. This time, the scientists are scanning the entire human genome to identify telltale variations between genes, rather than focusing on a set of known candidate genes.

Biology professor Mark Flood is heading a project to identify variations in genes involved in heart disease. He is shown in his lab at Fairmont State University in West Virginia with Sarah Dodson, assistant professor of biology (standing), and students (left to right) Contessa Hill and Bonnie Freeman. (Photo courtesy of Fairmont State University)

The two projects take full advantage of the resources at the collaborating institutions. Blood samples collected at the clinics are sent to Marshall University, where DNA is isolated from them. The DNA is then sent to Fairmont State University or West Liberty State University—two undergraduate institutions—to determine the nucleotide sequences of specific genes in each DNA sample. The sequence data are then analyzed at Marshall and West Virginia universities using bioinformatics tools to find significant associations between specific sequences and symptoms of heart disease. “The network helps with patient recruitment, but it also helps us bring together people with different expertise, which you need for these types of studies,” Primerano says.

Mark Flood, an investigator and professor at Fairmont State University, a three-hour drive from Marshall University, directs the familial combined hyperlipidemia study. “We would not have access to patient populations if we did not have these collaborations with Marshall and West Virginia University,” says Flood. “My campus has 7,500 undergraduate students; we don’t have a medical school or any chance to obtain funding for this kind of research unless we collaborate with investigators from larger institutions.”

One thing that makes the Appalachian population particularly well suited for these studies is that, in addition to the high prevalence of heart disease, individuals tend to live close to other family members. As a result, it is relatively easy for researchers to obtain DNA samples from several related individuals within a family, something that greatly aids genetic analysis. “We recently recruited a 22-member family at West Virginia University,” says Primerano. So far, the familial combined hyperlipidemia project has recruited about 50 participants, out of a possible 200 that will be needed to complete the study.

IDeA funding was used to buy specialized equipment at Fairmont—a pyrosequencer and several polymerase chain reaction (PCR) machines—and to hire another faculty member, relieving some of Flood’s teaching duties and freeing up more time for research. Students are also reaping the benefits. Since the start of the program, Flood has had 10 undergraduate students working in his lab, learning to do PCR and DNA sequencing. “We are seeing some successes with them getting into medical and graduate school or obtaining jobs in the biotech industry,” says Flood, adding that students are keen to work on the project because, for the first time, they are seeing the importance of their research to the health of their community.

Another outcome of the IDeA funding is that there is now an office of grants management at Fairmont. “We are seeing many more regional and national grants being submitted by our faculty, and our president has set aside money specifically to support undergraduate research,” says Flood.

NCRR’s Institutional Development Award (IDeA) program provides research opportunities, science education, and economic development and extends high-speed connectivity to grantee institutions to facilitate research collaborations. Twenty-three states and Puerto Rico participate in the program.