Stephanie Sherman, Professor in Genetics


What is the genetic etiology of mental retardation and other linked disorders? Stephanie Sherman, Professor of Genetics, is moving toward an answer. Sherman seeks to determine why certain errors during the formation of egg and sperm cause miscarriages or, for those women whose pregnancies make it to term, mental retardation and birth defects in their infants. This research centers on Down syndrome. Sherman also studies Fragile X syndrome, a form of mental retardation whose etiology is tied to a single gene. Better knowledge of the genetic bases of both disorders could begin to contribute to our understanding of the causes of mental retardation and, eventually, to possible treatments. Such understanding also promises to improve prognostic tools for identifying risks.

The National Down Syndrome Project
In partnership with the Centers for Disease Control, Sherman and her colleagues are completing a multi-site study of children born with Down syndrome and of their parents. The project uses cytogenetic, molecular, and epidemiological tools to examine trisomy 21, the chromosomal abnormality that causes over 95% of Down syndrome cases, and to explore its relation to maternal age. Sherman hopes to discover why older women have a greater risk of giving birth to children with Down syndrome than do younger women. "Right now we screen solely based on age," she says. "We want to be able to give more precise predictors for women." The project also explores genetic and environmental factors that contribute to birth defects in Down syndrome cases. Many children with Down syndrome are born with a 'hole in the heart,' also called atrioventricular septic defect. Sherman and her researchers have gone nationwide to identify 600 families with children (under age 18) who have suffered from this defect and another 600 who have a structurally normal heart. They have identified around 200 families in each group so far and actively are seeking more participants.

If the analyses go well, the same study design currently used for understanding birth defects also might be applied to behavioral and neurocognitive problems associated with Down syndrome. "We want to ask why some children with Down syndrome do quite well and others don't do well at all," Sherman says. "It's one of the struggles for their parents - how to incorporate their child into society." Though the neurobehavioral study is still in the feasibility stage, Sherman is intrigued by the possibilities. "If we can find the genetic variants that make a behavioral difference, then in the long run perhaps there might be a pharmaceutical intervention, or some other kind of therapeutic response, to help children with Down syndrome," she says.

The Emory Study of Adult Learning
Sherman and her team also study Fragile X syndrome, an inherited mental retardation caused by a single gene mutation. She leads the Emory Study of Adult Learning (ESAL), a genetic epidemiological study of persons with Fragile X and their families. Sherman's team analyzes the genetic connections between children who have Fragile X in its full mutation; their mothers, 20% of whom undergo premature ovarian failure (menopause before age 40); and their maternal grandfathers, who are prone to developing tremor ataxia syndrome, a late-onset neurodegenerative disorder that affects movement, thought, and behavior. "We're trying to figure out how all these things come together," Sherman says of Fragile X and its transmission across generations.

She remains especially committed to helping those women undergoing premature ovarian failure. Many undergo sudden menopause while they have young children - or while trying to have children - and the effects of the diagnosis can be devastating. Says Sherman: "I'd like to be able to have a prognostic marker, so that we could inform women while they're still young that they might be at risk for these fertility problems later in life."

Sherman, who mentors PhD students and post-doctoral fellows in the Genetics and Molecular Biology program, says Emory is a great place to do genetic research because it offers opportunities for creative collaboration. She is especially excited that Emory recently received an NIH Clinical and Translational Science Award, a program that she expects will facilitate clinical science at Emory. She works with researchers at the CDC, with faculty in Obstetrics and Gynecology, with families at the Georgia Fragile X Association and the Atlanta Down Syndrome Association. "The variety and ease of collaboration here at Emory is extremely advantageous," she says.

But the success of her work ultimately relies on those families who live with, and care for, children with Down syndrome and Fragile X. "Our research depends on these families letting us into their lives," Sherman says. "They're the ones who make the work happen." They also motivate the search for therapeutic interventions. Collaboration isn't just a search for scientific knowledge and scholarly conversation across academic departments. It also means translating new information into everyday practice and into the lives of families across generations.