Huda Zoghbi

Huda Yahya Zoghbi (Arabic: هدى الهبري الزغبي Hudā al-Hibrī az-Zughbī; born Huda El-Hibri; 20 June 1954) She was the editor of the Annual Review of Neuroscience from 2018 to 2024.

Her work helped elucidate the genes and genetic mechanisms responsible for a number of devastating neurological disorders, such as Rett syndrome and spinocerebellar ataxia type 1.

In 2017, she was awarded the Canada Gairdner International Award and the Breakthrough Prize in Life Sciences. She shared the 2020 Brain Prize with Adrian Bird for their work on Rett syndrome, and shared the 2022 Kavli Prize in Neuroscience, awarded "for pioneering the discovery of genes underlying a range of serious brain disorders".

Early life and education Huda Zoghbi was born in Beirut, Lebanon on 20 June 1954, and raised in Beirut. She loved reading works by William Shakespeare, Jane Austen and William Wordsworth in high school and intended to pursue literature at university. Zoghbi was admitted as a biological sciences major at the American University of Beirut (AUB) in 1973 and entered the university's medical school 2 years later. The war, however, raged on, and Zoghbi was under the impression that school terms at American medical schools began in October, as was the case with Lebanese schools. However, in October, it was confirmed that she was still unable to return to Lebanon due to the war, and US medical schools had begun their fall term 2 months earlier. Her family friends in America suggested she apply to Vanderbilt University. Vanderbilt did not accept transfer students, but recommended Meharry Medical College instead; Meharry accepted her on the spot. At present, Zoghbi is a professor at the Department of Molecular and Human Genetics at Baylor, with appointments as a professor at the Department of Neuroscience and the Department of Pediatrics Section of Neurology and Developmental Neuroscience, the Ralph Feigin, M.D. Endowed Chair, the director of the Texas Children's Hospital Jan and Dan Duncan Neurological Research Institute, a member of the Dan L. Duncan Comprehensive Cancer Center at Baylor, and an investigator at the Howard Hughes Medical Institute. attracted many Rett syndrome patients to Texas Children's Hospital, giving her access to a large number of cases.

Since most patients of Rett syndrome were girls, and symptoms were very consistent across patients, Zoghbi believed genetics were involved in the disease process.

Spinocerebellar ataxia type 1 Following the establishment of her own lab, Zoghbi continued studying spinocerebellar ataxia type 1 (SCA1), in collaboration with Harry Orr from the University of Minnesota. On the same day, 8 April 1993, both Zoghbi and Orr identified ATXN1 as the gene responsible for SCA1. Further work by Zoghbi, Orr and their teams demonstrated that the misfolding, aggregation, and proteasomal degradation of the protein product of this gene, Ataxin 1, played a role in the disorder.

Math1 After solving the etiology of spinocerebellar ataxia type 1, Zoghbi began studying animal genes related to balance. As Baylor's Hugo J. Bellen described the role of the atonal gene in balance in fruit flies (Drosophila), Zoghbi chose to study its mammalian homolog. A member of her lab successfully cloned the mouse homolog, Math1, in 1996. Her team went on to find that, in addition to its involvement in balance and coordination, Math1 is also crucial to hearing, the formation of secretory cells in the gut., and neonatal respiratory rhythm and chemosensitivity in the adult brain by regulating the development of a group of hindbrain neurons. Her lab has also shown that aberrant activation of Math1 could lead to medulloblastoma, a common childhood brain tumor, and that mice which did not express Math1, did not develop the tumor.

Rett syndrome

Since being Zoghbi was introduced to Rett syndrome early in her career, she has been working on the disorder alongside other research, despite the lack of enthusiasm from her colleagues, fellow researchers and funding agencies. The main reason is that very few individuals and even fewer families are available for investigation. In the 1990s, she collaborated with Uta Francke from Stanford University to identify the gene responsible for Rett syndrome. In 1992, she narrowed down the target to a section of the X chromosome. In 1999, a postdoctoral researcher in Zoghbi's lab identified MECP2 as the causative gene. The MECP2 protein binds methylated cytosine (5-methylcytosine) in CpG sites, and is indispensable for almost all brain cells. In 2009, she found mice deficient of the Mecp2 gene (the mouse homolog of human MECP2) had lower levels of norepinephrine, dopamine and serotonin, consistent with her clinical observations of patients of Rett syndrome in 1985. Recently, Zoghbi confirmed that the MECP2 protein also bound 5-methylcytosine not in CpG sites, and that restoring the level of MECP2 protein in a subset of neurons was sufficient to rescue some symptoms of Rett syndrome.

Ataxin-1 link to Alzheimer's After linking the gene Ataxin-1 to SCA1, Zoghbi's lab was approached by Dr. Jaehong Suh of the Massachusetts General Hospital's MassGeneral Institute for Neurodegenerative Disease to investigate the connection between ataxin-1 gene and Alzheimer's disease. The subsequent study found that loss of ataxin-1 elevates BACE1 expression and Aβ pathology in mouse models, rendering it a potential contributor to risk and pathogenesis of Alzheimer's disease.

Awards and honors

2026 – Louisa Gross Horwitz Prize 2026 – Nancy Lurie Marks Prize for Autism Research, inaugural recipient, awarded by the Lurie Autism Institute of Penn Medicine and Children's Hospital of Philadelphia. 2024 – Member of the American Academy of Sciences & Letters, invested at the Library of Congress in Washington, D.C., on 23 October 2024. 2022 – Kavli Prize in Neuroscience. 2020 – Brain Prize 2019 – Victor A. McKusick Leadership Award, American Society of Human Genetics 2018 – Member of the American Academy of Arts and Sciences 2018 – Ross Prize in Molecular Medicine, Molecular Medicine 2018 – National Order of the Cedar, Lebanon 2017 – Breakthrough Prize in Life Sciences 2017 – Canada Gairdner International Award 2016 – Jessie Stevenson Kovalenko Medal 2016 – Shaw Prize in Life Science and Medicine 2015 – Mechthild Esser Nemmers Prize in Medical Science, Northwestern University 2015 – Vanderbilt Prize in Biomedical Science, Vanderbilt University School of Medicine 2015 – Javits Neuroscience Investigator Award, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health 2015 – American Task Force for Lebanon Award 2015 – Mortimer D. Sackler, M.D. Prize for Distinguished Achievement in Developmental Psychobiology, Weill Cornell Medicine and Columbia University College of Physicians and Surgeons 2014 – Honorary Doctor of Medical Sciences, Yale University 2014 – March of Dimes Prize in Developmental Biology 2014 – Edward M. Scolnick Prize in Neuroscience, McGovern Institute for Brain Research, Massachusetts Institute of Technology 2013 – Dickson Prize in Medicine, University of Pittsburgh 2013 – Pearl Meister Greengard Prize, Rockefeller University 2011 – Gruber Prize in Neuroscience 2009 – International Rett Syndrome Foundation's Circle of Angels Research Award 2009 – Vilcek Prize for Biomedical Research, Vilcek Foundation 2009 – Marion Spencer Fay Award, Drexel University College of Medicine 2008 – Honorary Doctor of Science, Meharry Medical College 2008 – Texas Women's Hall of Fame 2007 – Massachusetts Institute of Technology Arab Students' Organization Science and Technology Lifetime Achievement Award 2007 – Honorary Doctor of Science, Middlebury College 2007 – Robert J. and Claire Pasarow Foundation Award in Neuropsychiatry Research 2004 – Member of the National Academy of Sciences 2004 – Neuronal Plasticity Prize, Ipsen Foundation 2004 – Marta Philipson Award in Pediatrics, Philipson Foundation for Research