Huda Zoghbi was enrolled in medical school at American University in Beirut when war erupted in Lebanon in 1975. When she went home after her first year, fully intending to return to school in the fall, she learned that her younger brother had been hit by shrapnel. He wasn’t badly injured, but Zoghbi’s parents decided to send her and her brothers to stay with relatives in the United States for the summer. The war escalated, she could not return home, and she transferred to Meharry Medical College in Nashville, Tennessee.
Zoghbi was nearing the end of her training as a pediatric neurologist when she met a young patient who changed her life. The five-year-old girl had developed normally until she was 18 months old, but now she had seizures and balance problems, constantly wrung her hands, and could not communicate. Unable to offer the girl’s parents any answers, Zoghbi set out to find some. She studied molecular genetics and dedicated her career to research.
Sixteen years later, Zoghbi’s team at Baylor College of Medicine identified a gene that, when mutated, causes Rett syndrome, the enigmatic disease Zoghbi first encountered in 1983. She later found that mutations in that gene, MECP2, can cause neurological problems beyond those typical of Rett syndrome and showed that the protein it produces is critical for mature neurons to function in the brain.
An HHMI investigator since 1996, Zoghbi now runs a lab that studies neurodevelopment and neurodegeneration from several different angles. Many neurodegenerative diseases—including Parkinson’s, Alzheimer’s, and Huntington’s—are caused by the buildup of toxic proteins in the brain. Zoghbi’s lab showed that the rare disease spinocerebellar ataxia (SCA1) is caused by the toxic protein ataxin-1. That research has had broad implications for the understanding of this class of diseases as well as for neurobiology.
Drugs that clear toxic proteins from the brain might improve symptoms in patients with such diseases. So with a Hughes Collaborative Innovation Award from HHMI, Zoghbi recruited a team of scientists with genetics and neurobiology expertise to explore an ambitious new approach to discovering targets for potential drugs. The strategy led the researchers to a signaling pathway that, when blocked, prevents the buildup of ataxin-1 in nerve cells, fruit flies, and mice with SCA1—a starting point for developing therapies.
Image: Bob Levey
About the HHMI Investigator Program:
HHMI investigators, appointed through rigorous competitions, are among the most creative and promising biomedical researchers in the nation. Each scientist receives long-term, flexible support, enabling them to follow their own curiosity in the pursuit of significant biological questions. The Investigator Program is the Institute’s flagship program, with an annual commitment of over $600 million dollars to support the investigators and their host institutions across the country. The collaboration between HHMI and these institutions powerfully extends the nation’s research capacity. Read more >>
About the Hughes Collaborative Innovation Awards:
HHMI’s belief in the value of multiple perspectives is exemplified by the Hughes Collaborative Innovation Awards (HCIA), which support interdisciplinary teams of scientists, each led by an HHMI investigator. The program encourages participants to pursue research with the highest transformative potential, even when the risk of failure is also high. Read more >>