QnAs with Huda Y. Zoghbi.

When neuroscientist Huda Zoghbi first came face-toface with Rett syndrome, she was well on her way to becoming a pediatric neurologist. Impelled by the plight of the patients and intrigued by the bizarre mix of symptoms that mark the syndrome, Zoghbi boldly decided to change course, setting aside her clinical career to seek training in molecular genetics. Over the years, Zoghbi’s efforts to unravel the molecular basis of Rett syndrome—a neurodevelopmental disorder characterized by loss of language, cognitive, motor, and social skills that mainly affects girls—have borne fruit. She pinpointed the gene responsible for the vast majority of cases, paving the way toward genetic diagnosis, counseling, and improved disease management. Along the way, Zoghbi’s work has paid surprising dividends on other neurologic and psychiatric disorders, such as autism and intellectual disabilities. More recently, her teamdemonstrated that electrical stimulation of neuronal circuits implicated in Rett syndrome partly reversed learning and memory deficits in a mouse model, raising a glimmer of hope for deep brain stimulation as a therapeutic approach. For her wide-ranging work on Rett and other neurodevelopmental disorders, Zoghbi, now a professor at Baylor College of Medicine, Houston, Texas, has garnered awealth of accolades, not least of which are membership in the National Academy of Sciences and the 2016 Shaw Prize in life sciences. PNAS caught up with Zoghbi on her decades-long work on Rett syndrome.