Zoghbi receives the prize in recognition of her work on the genetic basis of human brain disorders, in particular Rett Syndrome, a neurological disease that affects young girls (males with the condition usually die in infancy). Girls born with the disease develop normally for one or two years, but then begin to show progressive loss of motor skills, speech, and other cognitive abilities. Many of them also develop autism. In 1999, Zoghbi demonstrated that Rett syndrome is caused by deficiency in a protein called MeCP2, which binds methylated DNA and regulates the expression of many other genes.
Zoghbi’s discovery enabled the creation of mouse models that recapitulate many features of human Rett Syndrome, laying the groundwork for new therapies that are now undergoing clinical trials. Her recent work has focused on identifying the cell types and brain circuits that are responsible for the autistic-like behaviors of the mouse Rett model, which may represent promising targets for future therapeutic intervention.
In collaboration with a group in Minnesota, Zoghbi also identified the gene responsible for spinocerebellar ataxia type 1 (SCA1), a progressive neurodegenerative disease which, like Huntington’s disease, is caused by a pathological expansion of a repeated three-nucleotide sequence. The more times this is repeated, the earlier the onset of disease and the more severe the symptoms. The number of repeats can increase from one generation to the next, meaning that children are often more severely affected than the parent.
Zoghbi continues to study SCA1, and her recent work has focused on identifying genetic factors that slow the progression of the disease.
Zoghbi studied medicine in her native Lebanon and later in the United States, where she specialized in pediatric neurology. Following a postdoc stint in the laboratory of molecular geneticist Arthur Beaudet, she joined the faculty of Baylor College of Medicine in 1988. She is an investigator with the Howard Hughes Medical Institute, and the founding director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. She has received many honors for her work, including election to both the Institute of Medicine and the National Academy of Sciences.
The McGovern Institute will award the Scolnick Prize to Dr. Zoghbi on Wednesday, April 30. At 4:00 p.m., she will deliver a lecture titled, “A neural tipping point: MeCP2 and neuropsychiatric disorders,” which will be followed by a reception, at the McGovern Institute in the Brain and Cognitive Sciences Complex at 43 Vassar Street (building 46, room 3002 — Singleton Auditorium). The event is free and open to the public.