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Huda Y. Zoghbi, M.D.
Principal Investigator

  
         
 

Huda Y. Zoghbi is an investigator at the Howard Hughes Medical Institute, and a professor of Pediatrics at Baylor College of Medicine, Houston where she also is a professor of Molecular and Human Genetics, Neurology, Neuroscience, and faculty in the Developmental Biology, Cell and Molecular Biology, and Translational Biology and Molecular Medicine Graduate Programs.

A specialist in the study of development and neurogenetics, her work has encompassed many neurological disorders including the inherited degenerative balance disorders (spinocerebellar ataxias) and autism spectrum disorders such as Rett syndrome. The lab also investigates key and basic developmental questions about neuronal differentiation and development of the auditory and proprioceptive sensory system.

    Huda Y. Zoghbi  
       
 


After cloning the SCA1 and Rett syndrome genes, the Zoghbi lab has been dedicated to understanding the mechanism of pathogenesis of these disorders in hope of developing rational therapies that can be first tested in the animal models they have generated. Their overall strategy for studying neurological disorders is illustrated in Figure 1.

Strategy for studying neurological disorders
Figure 1

In a bottom-up approach, the Zoghbi lab identified the Math1 gene (mouse atonal homolog 1) and demonstrated its critical role for development of the auditory system (including inner ear hair cells), sensory balance (proprioception and vestibular system), respiratory control, and intestinal development. These basic developmental studies are beginning to provide insight about many human disorders (Figure 2).

Basic developmental studies
Figure 2

For the first 15 years of her career, Dr. Zoghbi spent 20 percent of her time seeing patients with childhood neurological disorders. Driven by a desire to improve the clinical outcome of her patients, she became convinced that more basic research is needed. In more recent years, as her research efforts expanded to understand the complex disease mechanisms, her clinical activities became limited with a focus on clinical research protocols that enroll selected patients. Dr. Zoghbi participates in teaching in the various graduate and clinical programs to which she belongs. Dr. Zoghbi’s favorite part of her job is interacting with graduate students, fellows, and other trainees in the lab.

Dr. Zoghbi cherishes her collaborations especially those long-standing ones with Harry T. Orr, Hugo Bellen, Juan Botas and more recently Nat Heintz.

  
 
Education:
Dr. Zoghbi was born in Beirut, Lebanon where she attended the American University of Beirut for her undergraduate studies.  She began medical school at AUB only to have her plans interrupted during her sophomore year when she was visiting family in the U.S. and could not return to Lebanon due to an escalating civil war.  She transferred to Meharry Medical College where she graduated in 1979.   Dr. Zoghbi then came to Baylor College of Medicine where she completed residency training in pediatrics and neurology and encountered her first Rett syndrome patient as a resident in 1983.  Her patients, particularly those with Rett syndrome, inspired her to pursue research training in molecular genetics.  She trained with Dr. Arthur L. Beaudet in the Department of Molecular and Human Genetics at Baylor College of Medicine.  Upon completion of her training in 1988, she joined the faculty of Baylor College of Medicine as an assistant professor.
  
 

Service:
Dr. Zoghbi is a member of several professional organizations and serves on the editorial boards of numerous prominent journals. She also serves on several scientific advisory panels including NINDS advisory council and the McKnight Endowment Fund for Neuroscience.

  
  Selected Memberships:
  • Institute of Medicine
  • American Association for the Advancement of Science
  • National Academy of Science
    		•   
     

    Selected Honors:
    Among her honors are:

    2009: International Rett Syndrome Foundation's Circle of Angels Research Award
    2009: Vilcek Prize for Biomedical Research
    2008: Honorary Doctorate of Science, Meharry Medical School, TN; Texas Women's Hall of Fame Award Texas Governor's Commission for Women Abilene, TX
    2007: Robert J. and Claire Pasarow Foundation Award in Neuropsychiatry, Los Angeles , CA; Honorary Doctorate of Science, Middlebury College, Middlebury, VT
    2006: Bristol-Myers Squibb Neuroscience Distinguished Achievement Award
    2004: Elected, National Academy of Sciences; Neuronal Plasticity Prize, IPSEN Foundation, Lisbon , Portugal; Marta Philipson Award in Pediatrics, Philipson Foundation for Research, Stockholm, Sweden
    2002: Raymond D. Adams Award, American Neurological Association; Elected Fellow, AAAS
    2001: Bernard Sachs Award, Child Neurology Society
    2000: Elected to the Institute of Medicine , National Academy of Sciences
    1998: Sidney Carter Award (American Academy of Neurology); Soriano Award, The American Neurological Association; Javits Award, NINDS Council, National Institutes of Health
    1996: E. Mead Johnson Award, Society of Pediatric Research
    1995: Kilby Award for Extraordinary Contributions to Society

    		  
     
    Personal:
    Dr. Huda Zoghbi is married to Dr. William Zoghbi, Professor of Cardiology, DeBakey Heart Center, at the Methodist Hospital, and is the proud mother of Roula Zoghbi (Middlebury College, class 2007) and Anthony Zoghbi (Washington University in St. Louis, Class of 2009).
    She is most grateful to her husband and children for unconditional love and support; her mentors for setting her on the right track; her friends for embodying what friendship is; her patients for their trust and participation; and her past and current lab members for their tireless efforts and for making the lab a fun and stimulating place.
    Dr. Zoghbi enjoys reading, working out, gourmet cooking (especially when she teams up with her daughter, a superb dessert chef), and the opera.
    		  
     

    Selected key publications:

    Akil H, Brenner S, Kandel E, Kendler KS, King MC, Scolnick E, Watson JD, Zoghbi HY. Medicine. The future of psychiatric research: genomes and neural circuits. Science. 2010 Mar 26;327(5973):1580-1. PubMed PMID: 20339051.

    Flora A, Klisch TJ, Schuster G, Zoghbi HY. Deletion of Atoh1 disrupts Sonic Hedgehog signaling in the developing cerebellum and prevents medulloblastoma. Science. 2009 Dec 4;326(5958):1424-7. Erratum in: Science. 2010 Mar19;327(5972):1454. PubMed PMID: 19965762.

    Rose MF, Ren J, Ahmad KA, Chao HT, Klisch TJ, Flora A, Greer JJ, Zoghbi HY. Math1 is essential for the development of hindbrain neurons critical for perinatal breathing. Neuron. 2009 Nov 12;64(3):341-54. PubMed PMID: 19914183; PubMed Central PMCID: PMC2818435

    Maricich SM, Wellnitz SA, Nelson AM, Lesniak DR, Gerling GJ, Lumpkin EA, Zoghbi HY. Merkel cells are essential for light-touch responses. Science. 2009 Jun 19;324(5934):1580-2. PubMed PMID: 19541997; PubMed Central PMCID: PMC2743005.

    Zoghbi HY. Rett syndrome: what do we know for sure? Nat Neurosci. 2009 Mar;12(3):239-40. PubMed PMID: 19238181.

    Ramocki MB, Zoghbi HY. Failure of neuronal homeostasis results in common neuropsychiatric phenotypes. Nature. 2008 Oct 16;455(7215):912-8. Review. PMID: 18923513; PubMed Central PMCID: PMC2696622.

    Lee Y, Samaco RC, Gatchel JR, Thaller C, Orr HT, Zoghbi HY. miR-19, miR-101 and miR-130 co-regulate ATXN1 levels to potentially modulate SCA1 pathogenesis. Nat Neurosci. 2008 Oct;11(10):1137-9. Epub 2008 Aug 31. PMID: 18758459; PubMed Central PMCID: PMC2574629.

    Fyffe SL, Neul JL, Samaco RC, Chao HT, Ben-Shachar S, Moretti P, McGill BE, Goulding EH, Sullivan E, Tecott LH, Zoghbi HY. Deletion of Mecp2 in Sim1-expressing neurons reveals a critical role for MeCP2 in feeding behavior, aggression, and the response to stress. Neuron. 2008 Sep 25;59(6):947-58. PMID: 18817733; PubMed Central PMCID: PMC2597031.

    Chahrour M, Jung SY, Shaw C, Zhou X, Wong ST, Qin J, Zoghbi HY. MeCP2, a key contributor to neurological disease, activates and represses transcription. Science. 2008 May 30;320(5880):1224-9. PMID: 18511691; PubMed Central PMCID: PMC2443785

    Lim J, Crespo-Barreto J, Jafar-Nejad P, Bowman AB, Richman R, Hill DE, Orr HT, Zoghbi HY. Opposing effects of polyglutamine expansion on native protein complexes contribute to SCA1. Nature. 2008 Apr 10; 452(7188):713-8. Epub 2008 Mar 12. PMID: 18337722; PMCID: PMC2377396

    Chahrour M, Zoghbi HY.The story of Rett syndrome: from clinic to neurobiology. Neuron. 2007 Nov 8;56(3):422-37. Review. PMID: 17988628

    Chao HT, Zoghbi HY, Rosenmund C. MeCP2 controls excitatory synaptic strength by regulating glutamatergic synapse number. Neuron. 2007 Oct 4;56(1):58-65. PMID: 17920015

    Bowman AB, Lam YC, Jafar-Nejad P, Chen HK, Richman R, Samaco RC, Fryer JD, Kahle JJ, Orr HT, Zoghbi HY. Duplication of Atxn1l suppresses SCA1 neuropathology by decreasing incorporation of polyglutamine-expanded ataxin-1 into native complexes. Nat Genet. 2007 Mar;39(3):373-9. Epub 2007 Feb 18. PMID: 17322884

    Lam YC, Bowman AB, Jafar-Nejad P, Lim J, Richman R, Fryer JD, Hyun ED, Duvick LA, Orr HT, Botas J, Zoghbi HY. ATAXIN-1 interacts with the repressor Capicua in its native complex to cause SCA1 neuropathology. Cell. 2006 Dec 29;127(7):1335-47.

    Serra HG, Duvick L, Zu T, Carlson K, Stevens S, Jorgensen N, Lysholm A, Burright E, Zoghbi HY, Clark HB, Andresen JM, Orr HT. RORalpha-mediated Purkinje cell development determines disease severity in adult SCA1 mice. Cell. 2006 Nov 17;127(4):697-708.

    McGill BE, Bundle SF, Yaylaoglu MB, Carson JP, Thaller C, Zoghbi HY. Enhanced anxiety and stress-induced corticosterone release are associated with increased Crh expression in a mouse model of Rett syndrome. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18267-72.

    Fryer JD, Zoghbi HY. Huntingtin's critical cleavage. Nat Neurosci. 2006 Sep;9(9):1088-9.

    Maricich SM, Zoghbi HY. Getting back to basics. Cell. 2006 Jul 14;126(1):11-5.

    Lim J, Hao T, Shaw C, Patel AJ, Szabo G, Rual JF, Fisk CJ, Li N, Smolyar A, Hill DE, Barabasi AL, Vidal M, Zoghbi HY. A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration. Cell. 2006 May 19;125(4):801-14.

    Zoghbi HY and Beaudet AL. 2006. Epigenetics and Human Disease. Reinberg D, Allis CD, Jenuwein T, eds. (New York: CSH Press).

    Beaudet AL and Zoghbi HY. 2006. A Mixed Epigenetic and Genetic and Mixed De Novo and Inherited Model for Autism. In Understanding Autism: From Basic Neuroscience to Treatment. Mouldin SO and Rubenstein JLR, eds. (CRC Press: Boca Raton, FL).

    Zoghbi, HY. 2006. Genetic Mechanisms in Degenerative Diseases of the Nervous System. In: Principles of Neural Science, 5th edition.  Kandel ER, Schwartz JH, Jessell TM, Siegelbaum S, and Hudspeth J, eds. (New York: McGraw-Hill).

    Moretti P, Levenson JM, Battaglia F, Atkinson R, Teague R, Antalffy B, Armstrong D, Arancio O, Sweatt JD, Zoghbi HY. Learning and memory and synaptic plasticity are impaired in a mouse model of Rett syndrome. J Neurosci. 2006 Jan 4;26(1):319-27.

    Wang VY, Rose MF, Zoghbi HY. Math1 expression redefines the rhombic lip derivatives and reveals novel lineages within the brainstem and cerebellum. Neuron. 2005 Oct 6;48(1):31-43.

    Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M. Towards a proteome-scale map of the human protein-protein interaction network. Nature. 2005 Oct 20;437(7062):1173-8.

    Tsuda H, Jafar-Nejad H, Patel AJ, Sun Y, Chen HK, Rose MF, Venken KJ, Botas J, Orr HT, Bellen HJ, Zoghbi HY. The AXH domain of Ataxin-1 mediates neurodegeneration through its interaction with Gfi-1/Senseless proteins. Cell. 2005 Aug 26;122(4):633-44.

    Ross MT et al. The DNA sequence of the human X chromosome. Nature. 2005 Mar 17;434(7031):325-37.

    Neul JL, Zoghbi HY. Rett syndrome: a prototypical neurodevelopmental disorder. Neuroscientist. 2004 Apr;10(2):118-28.

    Zoghbi HY. Postnatal neurodevelopmental disorders: meeting at the synapse? Science. 2003 Oct 31;302(5646):826-30.

    Zoghbi HY. Molecular neuroscience: BAC-to-BAC images of the brain. Nature. 2003 Oct 30;425(6961):907-8.

    Chen H-K, Fernandez-Funez P, Acevedo SF, Lam YC, Kaytor MD, Fernandez MH, Aitken A, Skoulakis EMC, Orr HT, Botas J, Zoghbi HY. Interaction of Akt-phosphorylated ataxin-1 with 14-3-3 mediates neurodegeneration in spinocerebellar ataxia type 1. Cell. 2003 May 16;113(4):457-68.

    Emamian ES, Kaytor MD, Duvick LA, Zu T, Tousey SK, Zoghbi HY, Clark HB, Orr HT. Serine 776 of Ataxin-1 Is Critical for Polyglutamine-Induced Disease in SCA1 Transgenic Mice. Neuron. 2003 May 8;38(3):375-87.

    Yoo S-Y, Pennesi ME, Weeber EJ, Xu B, Atkinson R, Chen S, Wu SM, Sweatt JD, Zoghbi HY.   SCA7 knockin mice model human SCA7 and reveal gradual accumulation of ataxin-7 neurons and abnormalities in short-term plasticity. Neuron. 2003 Feb 6;37(3):383-401.

    Shahbazian MD, Young  JI, Yuva-Paylor LA, Antalffy BA, Spencer CM, Noebels JL, Armstrong DL, Paylor R, Zoghbi HY. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3.  Neuron. 2002 Jul 18;35(2):243-54.

    Watase K, Weeber EJ, Xu B, Antalffy B, Nellis A, Yuva-Paylor L, Armstrong D, Sweatt JD, Orr HT, Paylor RL Zoghbi HY. A long CAG repeat in the mouse Sca1 locus replicates human SCA1 features and reveals the impact of protein solubility on selective neurodegeneration. Neuron. 2002 Jun 13;34(6):905-19.

    Yang Q, Bermingham N, Finegold M, Zoghbi H.  Requirement of Math1 for secretory cell lineage commitment in the mouse  intestine. Science. 2001 Dec 7;294(5549):2155-8.

    Bermingham NA, Hassan B, Fernandez M, Banfi S, Bellen H, Fritzsch B, Zoghbi HY. Proprioceptor pathway development is dependent on Math1.  Neuron. 2001 May;30(2):411-22.

    Fernandez-Funez P, Rosales MLN, de Gouyon B, She W-C, Luchack J, Turiegano E, Benito J, Capovilla M, Skinner PJ, McCall A, Canal I, Orr HT, Zoghbi HY, Botas J.  Identification of genes that modify ataxin-1 induced neurodegeneration.  Nature. 2000 Nov 2;408(6808):101-6.

    Matsuura T, Yamagata T, Burgess DL, Rasmussen A, Grewal RP, Watase K, Khajavi M, McCall AE, Davis CF, Zu L, Achari M, Pulst SM, Alonso E, Noebels JL, Nelson DL, Zoghbi HY, Ashizawa T. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10.  Nature Genet. 2000 Oct;26(2):191-4.

    Orr HT, Zoghbi HY. Reversing neurodegeneration: a promise unfolds. Cell. 2000 Mar 31;101(1):1-4.

    Hassan BA, Bermingham NA, He Y, Sun Y, Jan Y-N, Zoghbi HY, Bellen HJ. atonal regulates neurite arborization but does not act as a proneural gene in the Drosophila brain.  Neuron. 2000 Mar;25(3):549-61.

    Lin X, Antalffy B, Kang D, Orr HT, Zoghbi HY. Polyglutamine expansion down-regulates specific neuronal genes before pathologic changes in SCA1.  Nature Neurosci. 2000 Feb;3(2):157-63.

    Cummings CJ, Reinstein E, Sun Y, Antalffy B, Jiang Y-H, Ciechanover A, Orr HT, Beaudet AL, Zoghbi HY. Mutation of the E6-AP ubiquitin ligase reduces nuclear inclusion frequency while accelerating polyglutamine-induced pathology in SCA1 transgenic mice. Neuron. 1999 Dec;24(4):879-92.

    Lin X, Cummings CJ, Zoghbi HY. Expanding our understanding of polyglutamine diseases through mouse models. Neuron. 1999 Nov;24(3):499-502.

    Amir R, Van den Veyver IB, Wan M, Tran C, Francke U, Zoghbi HY. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2.  Nat Genet. 1999 Oct;23(2):185-8.

    Bermingham N, Hassan BA, Price SD, Vollrath MA, Ben-Arie N, Eatock RA, Bellen HJ, Lysakowski A, Zoghbi HY. Math1: an essential gene for the generation of inner ear hair cells.  Science. 1999 Jun 11;284(5421):1837-41.

    Klement, I. A., Skinner, P.J., Kaytor, M.D., Yi, H., Hersch, S.M., Clark, H.B., Zoghbi, H.Y., and Orr, H.T.  Ataxin-1 nuclear localization and aggregation: Role in polyglutamine-induced disease in SCA1 transgenic Mice.  Cell. 1998 Oct 2;95(1):41-53.

    Cummings, C. J., M. A. Mancini, B. Antalffy, D. B. DeFranco, H.T. Orr, H. Zoghbi. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat Genet. 1998 Jun;19(2):148-54.

    Ben-Arie N., H. J. Bellen, D. L. Armstrong, A. E. McCall, P. R. Gordadze, Q. Guo, M. M. Matzuk, and H. Y. Zoghbi.  Math1 is essential for genesis of cerebellar granule neurons. Nature. 1997 Nov 13;390(6656):169-72.

    Matilla, T., B. Koshy, C. J. Cummings, T. Isobe, H. T. Orr and H. Y. Zoghbi.  The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1.  Nature. 1997 Oct 30;389(6654):974-8.

    Skinner, P., B. Koshy, C. J. Cummings, I. A. Klement, K. Helin, A. Servadio, H. Y. Zoghbi, and H. T. Orr. Ataxin-1 with an expanded glutamine tract alters nuclear matrix-associated structures.  Nature. 1997 Oct 30;389(6654):971-4.

    Heintz N, Zoghbi H. alpha-Synuclein--a link between Parkinson and Alzheimer diseases? Nat Genet. 1997 Aug;16(4):325-7.

    Zhuchenko, O., J. Bailey, P. Bonnen, T. Ashizawa, D. W. Stockton, C. Amos, W. B. Dobyns, S. H. Subramony, H. Y. Zoghbi, and C. C. Lee. Autosomal dominant cerebellar ataxia (SCA6) associated with small polyglutamine expansion in the alpha1A-voltage-dependent calcium channel.  Nat Genet. 1997 Jan;15(1):62-9.

    Zoghbi HY. The expanding world of ataxins. Nat Genet. 1996 Nov;14(3):237-8.

    Burright, E. N., H. B. Clark, A. Servadio, T. Matilla, R. M. Feddersen, W. S. Yunis, L. A. Duvick, H. Y. Zoghbi, and H. T. Orr. SCA1 transgenic mice: a model for neurodegeneration caused by an expanded CAG trinucleotide repeat.  Cell. 1995 Sep 22;82(6):937-48.

    Chong, S. S., A. E. McCall, J. Cota, S. H. Subramony, H. T. Orr, M. R. Hughes, and H. Y. Zoghbi. Gametic and somatic tissue specific heterogeneity of the expanded SCA1 CAG repeat in spinocerebellar ataxia type 1.  Nat Genet. 1995 Jul;10(3):344-50.

    Servadio, A., B. Koshy, D. Armstrong, B. Antalffy, H. T. Orr, and H. Y. Zoghbi. Expression analysis of the ataxin-1 protein in tissues from normal and spinocerebellar ataxia type 1 individuals.  Nat Genet. 1995 May;10(1):94-8.

    Gouw, L. G., C. D. Kaplan, J. H. Haines, K. B. Digre, L. S. Rutledge, A. Matilla, M. Leppert, H. Y. Zoghbi, and L. J. Ptacek.  Retinal degeneration characterizes a spinocerebellar ataxia mapping to chromosome 3p.  Nat Genet. 1995 May;10(1):89-93.

    Banfi, S., A. Servadio, M-Y. Chung , T. J. Kwiatkowski Jr., A. E. McCall, L. A. Duvick, Y. Shen, E. J. Roth, H. T. Orr, and H. Y. Zoghbi. Identification and characterization of the gene causing type 1 spinocerebellar ataxia.  Nat Genet. 1994 Aug;7(4):513-20

    Chung, M-Y., L. P. W. Ranum, L. A. Duvick, A. Servadio, H. Y. Zoghbi, and H. T. Orr. Evidence for a mechanism predisposing to intergenerational CAG repeat instability in spinocerebellar ataxia type 1.  Nat Genet. 1993 Nov;5(3):254-8.

    Schaefer, L., G. B. Ferrero, A. Grillo, M. T. Bassi, E. J. Roth, M. C. Wapenaar, G. J. van Ommen, T. K. Mohandas, M. Rocchi, H. Y. Zoghbi, and A. Ballabio. A high resolution deletion map of human Xp22 region.  Nat Genet. 1993 Jul;4(3):272-9.

    Orr, H., M-Y. Chung, S. Banfi, T. J. Kwiatkowski Jr., A. Servadio, A. L. Beaudet, A. E. McCall, L. A. Duvick, L. P. W. Ranum, and H. Y. Zoghbi. Expansion of an unstable trinucleotide (CAG) repeat in spinocerebellar ataxia type 1.  Nat Genet. 1993 Jul;4(3):221-6.

    Chen, M., S. K. Mishra, H. Y. Zoghbi, R. W. Cottingham, H. T. Orr, H. M. Cann, and H. Donis-Keller. A comprehensive genetic linkage map of the human genome.  Science. 1992; 258:67-86.

     

    		  
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    Molecular and Human Genetics, Zoghbi laboratory
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    Last Modified: December, 2010