July 11, 1997

Lamb Center scientists take pediatric disease research to cellular level

Lamb Center scientists take pediatric disease research to cellular level

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Dr. Terence Dermody (second from left), works with graduate students (from left) Jim Chappell, Mehmet Goral and Jodi Connolly at VUMC's Lamb Center for Pediatric Research. Photo by Donna Marie Jones.

A vital component of Vanderbilt University Medical Center's continuing efforts to understand and treat childhood diseases is the Elizabeth B. Lamb Center for Pediatric Research.

There, investigators in three different laboratories work to unlock the mysteries of viruses by studying them at the cellular level, generating new knowledge that may one day lead to new and better treatments for diseases impacting children, said Dr. Terence S. Dermody, associate professor of Pediatrics and director of the Lamb Center.

"The key mission of the center is research and teaching. Through an understanding of how viruses target their host cells, enter those cells, replicate their genetic material and eventually kill the infected cell, we hope to create new avenues to develop antiviral drugs and vaccines.

"At the same time, we also train graduate students, medical students and fellows in fundamental research," Dermody said.

The center functions as one of the basic science arms of the Division of Pediatric Infectious Diseases, and consists of Dermody's laboratory as well as those of Dr. Mark R. Denison, assistant professor of Pediatrics, and Dr. Gregory J. Wilson, assistant professor of Pediatrics.

Dermody's lab studies reoviruses and focuses primarily on mechanisms of viral attachment to cells, disassembly of viral particles, genome replication, and pathogenesis. Denison's lab studies astroviruses and coronaviruses, concentrating on how these viruses replicate their genomes. Wilson's lab collaborates with Dermody's in studies of reovirus entry and disassembly while also focusing on the pathogenesis of HIV infection in children.

"Fundamentally, each of the Lamb Center laboratories is interested in how viruses cause neurologic diseases," Dermody said. "We're trying to answer a number of questions, such as how does the virus enter the body? How does it spread to the nervous system? How does it choose a particular cell to infect? How does it replicate? How does the targeted cell actually die? Does the body's immune response actually contribute to injury? Where, and how, can we intervene in this process to block it?

"These are the questions we're asking. We think some of the mechanisms will be general enough so that we can develop strategies to interfere with disease progression that could lead to the development of new antivirals," Dermody said.

The organization and working structure of the Lamb Center is unique among academic medical centers in the United States, Dermody said, thanks in large part to the center's close working relationship with the Department of Microbiology & Immunology.

"We enjoy a significant and substantial relationship with the department and with Dr. Jacek Hawiger, Oswald T. Avery Professor and Chair of Microbiology & Immunology.

"There are other well-funded labs around the country, but not a center. It's unusual to find so many basic molecular virologists housed within a clinical division doing research funded by the National Institutes of Health and training students and fellows.

"It really is a wonderful environment for the physician/scientist engaged in basic research with interests in teaching and clinical care," Dermody said.

The Lamb Center has come a long way since Dermody came to Vanderbilt seven years ago, growing far beyond his expectations.

"I wouldn't have envisioned this level of success seven years ago," Dermody said. "I wouldn't have anticipated three successful laboratories and the collaborative interactions we have been able to establish with other laboratories at Vanderbilt.

"We are making really important progress toward understanding fundamental mechanisms of how viruses use cellular machinery in order to replicate and how viruses ultimately kill their host cells, which are important phenomena to understand if the goal is to prevent virus-induced diseases."

The growth and success of the center is evidenced by George and Elizabeth Lamb. When it was established seven years ago, the Lambs agreed to provide funding for five years. Last year, they committed to another five years of funding.

"The strong commitment by the Lambs to the growth and development of the center has been crucial to our success," Dermody said. "When they established the center, the Lambs were very realistic. They knew a new drug or vaccine wasn't likely to be developed in two or three years. They understood that the clinical applications of basic research may take several years to be realized and that these applications may impact different fields.

"Most importantly, the Lambs realized that an equally vital mission of the center is to provide training in science."

Education plays a huge role in the Lamb Center's operation, as well as in the philosophy of creating new knowledge to combat childhood diseases, Dermody said.

"As important as our research is our responsibility to train graduate students to be effective scientists and to train medical students to be effective physicians. Our ultimate goal is that people who train here will emerge as leaders in their chosen fields.

"A significant component of the intellectual, creative energy that propels the research efforts of the Lamb Center comes from the students and fellows," Dermody said.

"They are the first ones to see the data. They come in and say 'See this result? See what this means? I think we need to test this hypothesis.'

"That's how a scientist thinks. They've made an observation, it suggests a model and they craft experiments to test it. My job is to make sure they've carefully thought through all the possible explanations and they've designed their experiments with the appropriate controls.

"They're the people who generate the new information. And they make the rest of us so much better through their creativity, critical thinking and dedication," Dermody said.