Lisa Guay-Woodford, M.D.
The baby came to Children’s Hospital in Boston with complex renal tubular disorder, and the house officer called for a series of tests to be run overnight. “He left me in charge to collect the data and samples and send them off to the labs to collect more data,” Dr. Lisa Guay-Woodford remembered.
At the time, she was in her third year at Harvard Medical School and was serving a pediatric rotation at the hospital. “It was an amazing experience. I hadn’t had a lot of research experience prior to that time, so I lacked the experience of seeing new information and puzzling out what might be wrong with this adorable little baby.”
After the testing was complete, Dr. Guay-Woodford sat down with the baby in the quiet of the night and fed her.
“I thought, this is exactly why I went to medical school,” she said. “It had elements of the intellectual snap, crackle, and pop; elements of the personal connection; and elements of trying to use a knowledge base to figure out someone’s problem and come up with a completely new insight. I was sold.”
In September 2005, Dr. Guay-Woodford, professor of medicine at the University of Alabama-Birmingham (UAB), was named director of the newly formed UAB
Recessive Polycystic Kidney Disease Core Center, a multidisciplinary center that will enhance understanding of autosomal recessive polycystic kidney disease (ARPKD), a genetic kidney disorder.
The disease occurs in one in 6,000 to 40,000 people, with a higher incidence in Finlanders and Afrikaners. The disease is characterized by cyst formation in the kidney and bile duct abnormalities and is chronic and progressive and causes liver abnormalities and eventual kidney failure. Approximately 50 percent of people with the disease are diagnosed prenatally. There is no cure and up to half of newborns diagnosed with the disease die soon after birth.
“This is a rare disorder, and there are not a lot of patients,” she said. “We’re trying to figure out how the disrupted gene causes this disease. From there, we can determine specific therapies.”
By using a mouse model to locate the pathways of the gene mutation Dr. Guay-Woodford hopes to provide insights that can be used to understand and perhaps treat the disease in humans.
UAB maintains a registry for ARPKD patients and has one of four participating laboratories in an international ARPKD Consortium that identified the single gene that causes the disease. In related work, Dr. Guay-Woodford’s group has characterized two distinct mouse models, in which the clinical disease closely resembles human ARPKD. Her laboratory has identified the genes for both models and recently, her group has identified a candidate modifier gene for one of the models.
Other genetic diseases, such as sickle cell disease and cystic fibrosis (CF), are caused by a mutation on one gene. Though 70 percent of CF patients have the same mutation, there is a wide range of clinical disease expression.
“It was logical to look at the disease process in the mouse model and ask, is this same process happening in human kidney disease?” Dr. Guay-Woodford says. “In the mouse model that we study all affected mice share two copies of the same mutation, but they have very different levels of disease expression. So we are not only interested in characterizing the gene disrupted in the disease, we are also looking to identify other genetic factors that could be affecting the disease in the mouse.”
UAB’s center will serve as a unique resource to design and develop studies involving mechanisms of the disease, to enhance diagnostic specificity, and to expand therapeutic approaches.
“One nice thing is that so much of biomedical research is involved in building a foundation,” Dr. Guay-Woodford says. “Following the logical steps—seed money, grants from organization like the Burroughs Wellcome Fund, and support from the National Institutes of Health—all of these things can be put together on a platform from which you can build a superstructure that can have increasing impact and importance in terms of scientific insight and translation to meaningful clinical impact.”
By Russ Campbell, BWF communications officer