Not only do HIV and AIDS patients receive medical care at the VA, they are living longer and have renewed hope for a cure directly because of the work of VA-based Emory scientists. One of the most notable accomplishments was the nucleoside analog 3TC, one of the prime ingredients in the now famous antiHIV drug "cocktail."

Since the 1980s, chemist/virologist Raymond Schinazi, who is also a professor of pediatrics at Emory, has worked with former Emory vice president of research Dennis Liotta to develop 3TC and other novel drugs to fight HIV and AIDS. One of their discoveries, another nucleoside analog, fluorothiacytidine (FTC), appears to shut down HIV's ability to reproduce. The drug, now in Phase I/II clinical trials, also may be effective against another as yet incurable disease -- hepatitis C.

Despite the good news over the past decade that multiple drugs can help HIV and AIDS patients, researchers have also learned such drugs can't always be relied on indefinitely -- drugs that once worked can stop doing their job. Emory/VA investigators have successfully found a new tactic to fight the problem of drug resistance in these patients.

David Rimland, director of the VA's AIDS and HIV Research Center and Emory professor of medicine, devised a way to look at the gene sequence of the virus and then search for mutations at specific sites associated with known resistance to drugs. Simply put, he can see which drugs will work and which won't in individual patients.

"As we treat patients, we want to be able to measure drug resistance so we can change therapy and do what needs to be done to help these people stay as healthy as possible," says Rimland.

The VAMC offers one of the largest
research subject populations anywhere
for Emory/VA scientists such as David
Rimland (above), and Janet Rubin, Joseph
Ouslander, and Peter Thulé (below).

Currently, she's heading a team of VA-based Emory investigators including orthopedist Scott Boden and endocrinologists Mark Nanes and Louisa Titus. They are deciphering the intracellular signals that tell the body to turn bone growth off or on. "We've found that we can keep osteoclasts (cells that reabsorb bone) from forming by mechanically stimulating cultured marrow cells," Rubin explains. "We've shown that two signal transduction pathways are involved."

But how do cells "hear" mechanical signals? If they can find out -- and learn how osteoclasts respond to these signals, the Emory/VA scientists hope to eventually apply the knowledge to therapies for osteoporosis. And the interpretation of these cells' "language" may eventually be used to help weightless astronauts retain bone mass while on prolonged space flights.

The VA has been a visionary leader in geriatric care, teaching, and research for more than 20 years through its geriatric research education and clinical centers, says Joseph Ouslander, director of geriatric medicine and gerontology at Emory. He also directs the VAMC's Rehabilitation Research and Development Center where 20 full-time staff, most with Emory faculty appointments, research the rehabilitative needs of older vets, especially those with disabilities, that range from dementia and sexual dysfunction to joint diseases.

Ouslander's current research focuses on frail older residents in VA nursing homes. He wants to know if a combination of continence management and low-intensity exercise (which he's dubbed "FIT" for functional incidental training) can help their quality of life. The multisite study involves VA medical centers across the country.

This ability for Emory/VA researchers to tap into patient populations at other veterans hospitals for research subjects is another advantage of the Emory/VA partnership. "The veterans administration offers one of the largest subject populations of any place. With 172 hospitals, that adds up to a huge number of patients," says Bruce Blasch, coordinator of the VAMC's aging sensory research program in the Rehabilitation Research and Development Center.

One project Blasch is working on with principal investigator Bill De l'aune, in fact, involves more than 5,000 subjects drawn from the national VA hospital patient population. "We are asking 13 questions in a phone survey to see how people are really functioning after rehab for their blindness. Can they dial a phone? Make a sandwich? It is a huge project and may well be the largest survey of its kind in the world, thanks to our ability to access the VA patient population nationally," Blasch says.

The collaboration between the VA and Emory makes Blasch's work rich in possibilities and resources. "It's a great combination," he says. "The VA offers researchers enormous opportunities, and Emory gives us the chance to expand the scope of our professional expertise. We have geriatricians, ophthalmologists, rehab medicine, and more -- colleagues we can work jointly with and expand the scope of our research."

As a clinical and research fellow at Emory five years ago, Thulé applied for funding to various government agencies -- primarily the NIH. "I was repeatedly denied," he says. "Then the VA saw some wisdom in my work and decided to support it."

Type I diabetes is characterized by the loss of cells in the body that produce insulin. Because this defect is caused by the lack of a single protein, Thulé began studying the concept of administering a gene to produce this one protein in hope that it would cure the disease. Other researchers had prompted liver cells to produce human insulin in rats, but the insulin production was not regulated and the amount of insulin produced didn't change with meals or fasting.

Working at the VAMC's state-of-the-art genetics lab, Thulé placed a gene he designed that regulated the amount of insulin produced from rat livers into a virus (modified so it could not replicate and was no longer dangerous) and injected it into the blood vessels of severely diabetic rats. In three to four days, the animals' livers were producing enough insulin to control their blood sugar levels, and the insulin was regulated. This young physician/scientist had come up with an astounding diabetes cure in an animal model.

"It worked out much better than I had hoped," says Thulé. "The dream is to try this on humans, of course. But the first step is to work up to pigs and then, nonhuman primates." Because of ongoing VA support, Thulé will be able to continue this important research.

From the Director  /  Letters

On the front lines of health care

Half century of cooperation (photos)

Research: The VA's secret weapon

Designer medicine

Moving Forward  /  Noteworthy

Unfinished business: The prospects for health care reform in the 107th Congress

Looking for greener pastures