HomeAdvance ScienceHuda Zoghbi – The Roots of Neurodegeneration
Huda Zoghbi – The Roots of Neurodegeneration

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 and Zoghbi could not return home, so 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 girl had developed normally until she was 18 months old, but by age 5 she was experiencing seizures and balance problems, was constantly wringing 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, MECP2, that, when mutated, causes Rett syndrome, the enigmatic disease Zoghbi first encountered in the young patient. She later found that mutations in MECP2 can cause neurological problems beyond those typical of Rett syndrome, and showed that the protein encoded by the gene 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. Zoghbi’s research on Rett syndrome and SCA1 garnered a 2017 Breakthrough Prize in Life Sciences.

A foray into neurodevelopment also led Zoghbi to discover a gene called mouse atonal homolog 1 (Math1 or Atoh1). The gene is essential for the creation of components of the auditory, proprioceptive, and interoceptive systems, as well as secretory cells in the gut and sensory cells in the skin; it is also involved in the development of neurons critical for neonatal breathing. Zoghbi’s team is now dissecting Atoh1’s molecular functions and its role in regulating breathing.

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 >>