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Zoghbi shares Shaw Prize for research leading to discovery of genes and proteins involved in Rett syndrome.
Investigator, Baylor College of Medicine
Zoghbi shares Shaw Prize for research leading to discovery of genes and proteins involved in Rett syndrome.


 

The Shaw Prize Foundationexternal link, opens in a new tab in Hong Kong announced that Huda Y. Zoghbi, a Howard Hughes Medical Institute investigator at Baylor College of Medicine, has been awarded the 2016 Shaw Prize in Life Science and Medicine.

Zoghbi shares the $1.2 million award with Adrian P. Bird of the University of Edinburgh. The two were honored for their discovery of the genes and proteins involved in the developmental disorder Rett syndrome.

The Shaw Prize consists of three annual awards in astronomy, life science and medicine, and mathematical sciences. These international awards honor individuals who have achieved distinguished breakthroughs in academic and scientific research. The awards are dedicated to furthering societal progress, enhancing quality of life, and enriching humanity’s spiritual civilization. The 2016 prizes will be presented to recipients later this year at a ceremony in Hong Kong.

The Shaw Prizes were established under the auspices of the late Sir Run Run Shaw, a Hong Kong film producer and chairman of Television Broadcasts Limited (TVB), the largest Chinese program producer in the world.

Learn about Huda Zoghbi’s childhood in Lebanon and how her interests shifted from pediatric cardiology to neurological disorders in this video from HHMI’s BioInteractive.

 

Rett syndrome is the leading cause of mental retardation in girls. First recognized as a syndrome in the 1980s, the disorder affects one in 10,000-15,000 girls. It is particularly devastating for families with affected children because infants are seemingly normal at birth and achieve the usual developmental milestones for the first few months of life. Then, as the infant reaches toddlerhood, a sudden and dramatic decline in physical and mental capabilities takes hold, accompanied by onset of seizures, irregular breathing, awkward gait, and hand-wringing.

Zoghbi has been studying Rett syndrome since the mid-1980s, when she first encountered patients with the disorder as a neurology fellow and decided to search for the gene responsible for the disorder. She reasoned that the gene must be on the X chromosome, the female sex chromosome, and it must also be essential because there had been no males reported to have the syndrome.

After 14 years of searching, a scientist in Zoghbi’s lab found that a gene called MECP2 was mutated in the Rett Syndrome patients they studied. Earlier research suggested that the MeCP2 protein was responsible for making sure that genes the cell has marked with a molecular tag, called a methyl group, are silenced. The MeCP2 protein latches on to these methyl groups and prevents them from being translated into protein.

How MeCP2’s molecular role translates into a neurological disorder is still not clear. However, research indicates that mutations in the MECP2 gene can take a wide variety of forms. “We now know of cases of classic autism and schizophrenia that are caused by mutations in this gene,” said Zoghbi. “The clinical spectrum is so broad that we don’t know the true prevalence of this mutation.” She estimates that the mutation may be twice as common as is currently thought, with perhaps one in 10,000 children affected.

What is clear so far is that the MECP2 gene, which resides at the end of the long arm of the human and mouse X chromosome, plays a vital role in fine-tuning the developing nervous system during a crucial stage when infants are learning to sit up, walk, and begin language acquisition, said Zoghbi.

To understand the molecular details of what goes wrong, Zoghbi and her colleagues created a mouse model that faithfully recapitulates Rett syndrome, down to its distinctive hand-wringing behavior. Using the mouse model, the scientists are probing how the MeCP2 protein affects brain function at a crucial developmental stage.

Zoghbi is hopeful that the mouse model will also have implications for the treatment of patients diagnosed with Rett Syndrome. “I could envision that with interventional studies in mice, we may identify pathways that could lead to behavioral or pharmacological approaches that may provide at least symptomatic relief,” said Zoghbi.