Dr. Huda Zoghbi, professor of neuroscience, pediatrics, molecular and human genetics and neurology at Baylor College of Medicine, will receive the 2014 March of Dimes Prize in Developmental Biology, an award given annually to investigators whose research has profoundly advanced the science that underlies the understanding of birth defects.
Zoghbi, who is also the founding director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital and a Howard Hughes Medical Institute investigator, is best known for her pioneering work on Rett syndrome, a genetic 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.
“Dr. Zoghbi’s contributions to our understanding of several entirely different neurological disorders, including her finding of the genetic basis of Rett syndrome, have opened new areas of research,” says Dr. Joe Leigh Simpson, senior vice president for Research and Global Programs at the March of Dimes. “Her work influences the entire field of autism and other neuropsychiatric disorders.”
Zoghbi has been committed to searching for the genetic cause of the syndrome – a very challenging task – since she first encountered children with Rett syndrome in her residency. She persevered through challenges associated with the not widely recognized syndrome including misdiagnosis and isolated sporadic mutations. After a 16-year search, in 1999 she succeeded in identifying the Rett gene.
This discovery provided a definitive genetic diagnosis for the condition and also opened the door to a biological understanding and a search for treatment. 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. The gene lies on the X chromosome, and in females one of the two X chromosomes is randomly inactivated in each cell; thus each patient with the Rett mutation has a different pattern of healthy and mutant cells, explaining some of the variability of Rett symptoms.
Identification of the Rett gene allowed researchers to make equivalent mutations in mouse models, which develop progressive neurological symptoms strikingly similar to those of human patients. This in turn laid the groundwork for further studies by Zoghbi and other researchers and to the development of new therapeutic strategies that are now undergoing clinical trials.
Given annually, the March of Dimes Foundation created the prize in 1995 as a tribute to Dr. Jonas Salk, a pioneer in the development of the polio vaccine.
Zoghbi will deliver the 19th annual March of Dimes Lecture titled “Rett Syndrome and MECP2 Disorders: From the Clinic to Genes and Neurobiology,” during the Pediatric Academy Societies annual meeting May 5 in Vancouver. She will receive the March of Dimes Prize in Developmental Biology in a special award ceremony held during the meeting.
The March of Dimes Foundation is the leading nonprofit organization for pregnancy and baby health.