2026 Horwitz Prize Awarded for Work on Epigenetics in Neurological Diseases

Dr. Huda Zoghbi, Distinguished Service Professor and Howard Hughes Medical Institute Investigator at Baylor College of Medicine and founding director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital, along with her long-time collaborator Dr. Adrian Bird, professor at the University of Edinburgh, will be awarded the prestigious 2026 Louisa Gross Horwitz Prize from Columbia University for their pioneering work on epigenetic regulation in the nervous system and its role in human neurological disease, particularly Rett syndrome.

“We are immensely proud to see Dr. Huda Zoghbi and her long-time collaborator Dr. Adrian Bird recognized with this award. It is a fitting recognition of the extraordinary scientific vision they have built upon through decades of collaboration and research,” said Dr. Jakob Tolar, president, CEO and executive dean of Baylor. “Dr. Zoghbi exemplifies Baylor College of Medicine’s commitment to improving health through discovery. Her work has been at the forefront of scientific advancement, not just changing the way we understand neurological disease, but giving families hope.”

Primarily affecting girls, Rett syndrome is a severe neurodevelopmental disorder that impacts nearly every aspect of life, including the ability to speak, walk, control hand movements, eat, breathe, think and control seizures. Before the discoveries of Zoghbi and Bird, the disorder was poorly understood and considered untreatable. Today, with lifelong support, individuals with Rett syndrome can live well into adulthood.

Bird uncovered key principles of epigenetic regulation, a chemical process that turns genes on and off without altering their underlying code. In the 1980s, he discovered CpG islands, specialized DNA clusters present near the start of genes. A decade later, his lab identified MeCP2, a protein that scans for chemical tags called methyl groups attached to these clusters and, upon finding them, switches the nearby gene off, acting like a molecular “off switch” for gene activity in neurons and throughout the body.

Zoghbi discovered in 1999 that mutations in MeCP2 cause Rett syndrome, establishing the first direct link between epigenetics and a severe neurological disorder and enabling early detection of the disease by genetic testing. She also showed that MeCP2 levels must be precisely maintained for neurons to function normally. Too little MeCP2 causes Rett syndrome, while doubling MeCP2 levels causes neurological deficits. Later work revealed that MeCP2 mutations also contribute to a range of other neurological conditions, from autism to juvenile-onset schizophrenia.

Though Rett syndrome was thought to cause permanent brain damage, Zoghbi and Bird showed that it could be reversible. Bird’s group engineered the first mouse model of Rett syndrome and, in 2007, showed that reactivating MeCP2 in these mice dramatically improved neurological symptoms. Zoghbi’s team showed that the effects of abnormal levels of functional MeCP2 can be reversed in mice by oligonucleotide therapy. Based on this work, a new generation of gene replacement (TSHA-102 and NGN-401) and RNA-regulating (ION 440) drugs, are now advancing through clinical development.

“Together, these two scientists have forged a remarkable path from fundamental discovery to therapeutic possibility, exemplifying the highest ideals of biomedical research,” said Laura Landweber, chair of Columbia’s Horwitz Prize committee.

“Their collective work has transformed our understanding of the molecular basis for a significant human disease and brought renewed hope to patients and families affected by devastating neurological disorders,” added Henry Colecraft, a member of the prize committee.

Zoghbi and Bird are the 122nd and 123rd winners of the Horwitz Prize, which is awarded annually by Columbia University for groundbreaking work in medical science. Of the 121 previous Horwitz Prize winners, 55 have gone on to also receive Nobel Prizes.