Genetic studies in mice and fruit flies have shed the most light on SCA1 pathogenesis. Genome annotation related files including junction database (known … Research Area: Pathogenesis of neurodegenerative disease, Rett syndrome, normal neurodevelopment, Ataxin-1, Akt, Mouse models (PI: Huda Zoghbi)... Huda Zoghbi Lab Skip to main content The laboratory uses genetic, biochemical, and cell biological approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases and Rett syndrome, and to study genes essential for normal neurodevelopment. Our analysis of SCA1 transgenic mice revealed that the mutant protein aggregates in the nuclei of cerebellar Purkinje cells and that these aggregates stain positively for ubiquitin, the proteasome, and some chaperones. Huda Zoghbi, MD | Baylor College of Medicine. Our analysis of the cellular distribution of MeCP2 during development determined that MeCP2 is in mature neurons and that the number of MeCP2-positive cortical neurons increases up to 10 years of age in humans. Davut Pehlivan, MD, Instructor of Neurology at Texas Children’s Hospital, studies translational neuroscience because of the kids with brain disorders he has seen in the clinic. Huda Zoghbi Lab. Huda Zoghbi wants to understand the mechanisms underlying brain development and degeneration. Dr. Huda Zoghbi Baylor College of Medicine. Immigrants make the journey to the United States for a number of reasons. To our surprise we found that several ataxia proteins interact directly or indirectly and that certain RNA-binding proteins and transcription regulators form key hubs in the ataxia network. Reprints. In 1999, Dr. Huda Zoghbi identified the defective gene, MECP2, that causes Rett Syndrome, Legendary Care . Plasmid pLenti-DsRed_IRES_MAPT:EGFP from Dr. Huda Zoghbi's lab contains the insert DsRed-IRES-MAPT-EGFP and is published in Elife. We also generated transgenic mice that overexpress MeCP2 at twice the normal level in the correct spatiotemporal distribution, and found that they develop a progressive postnatal neurodevelopmental disorder. Lastly, we recently found that the Ataxin-1 paralog (Ataxin-1 like) can suppress neurodegeneration in the SCA1 knock-in mice by displacing Ataxin-1 from its native complex facilitating its sequestration into inclusions. ©1998-2020 Baylor College of Medicine® | One Baylor Plaza, Houston, Texas 77030 | (713)798-4951Have an edit or suggestion for this page? Content. October 2, 2020. Diese ambitionierte Einrichtung befindet sich im Herzen des Texas Medical Center, ganz in der Nähe des … Working primarily in mouse models and humans, Zoghbi and her team study the activities of proteins involved in neuropsychiatric disorders such as Rett syndrome, MECP2 duplication syndrome, and mania. Take Dr. Huda Zoghbi’s decade-long study on the genetic origins of Rett syndrome as a starting point. Institute for Clinical & Translational Research, Department of Molecular and Human Genetics, Section of Neurology and Developmental Neuroscience. Email. Huda Y. Zoghbi, M.D. Alumni Today; Research Areas. Our laboratory uses genetic, cell biological, and biochemical approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases, the function of Math1 in neurodevelopment, and how MECP2 mutations cause postnatal neurodevelopmental disorders. $1,485,949 AWARDED. Our ultimate goal is to correlate phenotypes to specific neurons and to identify the gene expression changes within such neurons that could be modulated to modify the phenotypes. UTD Green Fellow. Call today to schedule an appointment or fill out an online request form. For … We created a mouse model that expresses the glutamine-expanded Ataxin-1 under the control of endogenous locus (knock-in SCA1 mice) and found that this model recapitulates all features of SCA1. If requested before 2 p.m. you will receive a response today. In her laboratory at Baylor College of Medicine, Dr. Huda Zoghbi and her colleagues have found two neuronal lineages in the hindbrain that act as ‘conductors’ of an exquisite biological symphony. Located on the X chromosome, MECP2 encodes a protein that binds methylated cytosines, helping to orchestrate gene silencing via DNA methylation. Have an edit or suggestion for this page. Content . Zoghbi said she was not expecting so many children, the majority being young girls, to reach out to her to say how they had never thought that a career in science and medicine could be just as glamorous as the lives of celebrities they see on the red carpet and even more rewarding. This finding suggested that the symptoms of Rett syndrome were caused by a defect in the function of MECP2: controlling the activity of other genes. America's fourth largest city is a great place to live, work and play. Huda Y. Zoghbi (Howard Hughes Medical Institute, Baylor College of Medicine) epigenetic and transcription regulation in neural development and diseases. Although there was considerable interest in MeCP2, the protein only really gained the spotlight in 1999, when Huda Zoghbi’s lab at Baylor College of Medicine in Houston identified it as the protein involved in Rett syndrome, a severe and progressive brain disorder (Amir et al., Nature Genetics 1999). Dr. Marvin Fishman with Dr. Huda Zoghbi in her lab. The Huda Zoghbi Lab has deposited plasmids at Addgene for distribution to the research community. This led us to propose that wild-type Ataxin-1 might take on a conformation that resists clearance or interacts strongly with other proteins and that such conformation is favored by the expanded polyglutamine tract. Second, we found that the AXH domain in Ataxin-1 is a key mediator of the neuropathology in part through interactions with the transcriptional repressors Gfi-1 and Capicua. Math1 is also essential for secretory cells in the gut (Paneth, goblet, and enteroendocrine cells), and the enteroendocrine cells secrete neuropeptides that modulate gut proprioception. That a single gene controls the genesis and/or differentiation of multiple components of the proprioceptive pathway was a surprise. We tested this hypothesis in cells, fruit flies, and mice and found that indeed chaperone overexpression mitigates SCA1 neuropathology and phenotypes. Heading. 1985-1989; 1990-1999; 2000-2009; Contact Us. Dust off the crystal ball: It’s time for STAT’s 2020 Nobel Prize predictions. Identification of the Math1-dependent neurons allowed us to propose that Math1 redefines the rhombic lip and its derivatives. This plasmid is available through Addgene. email@example.com. Girls affected with Rett syndrome appear to develop normally for the first 6 to 18 months of life, then lose the ability to speak and socialize, and develop tremors, ataxia, seizures, and stereotypic hand-wringing movements. This proved to be the case. The glutamine tract seems to mediate its toxicity by modulating the activity of the AXH domain. Dr. Zoghbi and her collaborators have unraveled the genetic underpinnings of a number of devastating neurological disorders, including Rett syndrome and spinocerebellar ataxia type 1 (SCA1). Neither of her parents went to college, but her father, who worked from the age of 17 as an extractor of olive oil, was a self-taught scholar. Recently we found that MeCP2 regulates the expression of corticotropin-releasing hormone (CRH) by binding the promoter of the Crh gene. Access our COVID-19 Response homepage, with more information and resources during the COVID-19 pandemic, including what to do if … We are treating Mecp2308 mice with Crh receptor-1 antagonist to determine if this will subdue the anxiety and stress phenotypes. Mice lacking Math1 die at birth because they cannot initiate respiration. Huda Zoghbi Lab... COVID-19 Response. We and others have discovered that MECP2 mutations cause a broad spectrum of phenotypes in both females and males. Have an edit or suggestion for this page. 2018 -2020. now medical student . ©1998-2020 Baylor College of Medicine® | One Baylor Plaza, Houston, Texas 77030 | (713)798-4951Have an edit or suggestion for this page? Postdoctoral fellow, Huda Zoghbi lab, Baylor College of Medicine, Houston, TX Michael Borten firstname.lastname@example.org: Undergraduate Student (2014–2016) Lab Specialist (2016–2017) Medical Student, University of Virginia Joey Bose, MS email@example.com: Undergraduate Student (2008–2011) Lab specialist (2011-2012) Find out why.Get to Know Houston. MECP2-duplication syndrome (MDS) occurs when there are one or more extra copies of the MECP2 gene. This basic research effort discovered that mutations in the MECP2 gene cause Rett syndrome. Contact. For other genome builds please use this MakeGeneModel script to generate the annotation model files. In collaboration with Juan Botas (Baylor College of Medicine), we found that high levels of wild-type Ataxin-1 produce effects similar to mutant Ataxin-1 in Drosophila and mice. The Blue Bird Circle Rett Center is the largest clinic in the world dedicated to the diagnosis, treatment and follow-up care of those with this condition. Fax. In collaboration with Harry Orr's group (University of Minnesota), we determined that the mutation responsible for SCA1 is an expansion of a CAG trinucleotide repeat encoding glutamine in the protein Ataxin-1. Die Leiterin Huda Zoghbi, deren Labor feststellte, dass Mutationen an MECP2 das Rett-Syndrom auslösen, stellt sich ein Forschungszentrum vor, wo Wissenschaftler mit verschiedenen Interessen in einem Umfeld des kontinuierlichen und interdisziplinären Austauschs arbeiten können. Dr. Huda Y. Zoghbi is a professor in the Departments of Pediatrics, Molecular and Human Genetics, Neurology and Neuroscience at Baylor College of Medicine. She and her classmates ate in the hospital cafeteria, which they accessed through an underground tunnel. Institute for Clinical & Translational Research. Sharon Y. Dent (Center for Cancer Epigenetics, M. D. Anderson Cancer … In an interview with ... She began her independent lab studying the adult-onset neurodegenerative disease spinocerebellar ataxia type 1 and branched out to study other neurodegenerative conditions. 713–798–6558. Her lab also studies postnatal neurodevelopmental disorders, most … Humay (Gulhumay) Gardashova . Baylor College of Medicine will be closed on Monday, Jan. 18 in observance of Martin Luther King, Jr. Day. She started her studies in biological sciences and did one year of medical school at the American University of Beirut in Lebanon. Dr. Huda Y. Zoghbi’s lab works hand-in-hand with The Blue Bird Circle Rett Center at Texas Children’s Hospital to provide cutting edge treatment for girls and women with Rett syndrome. We isolated the mouse atonal homologue 1 (Math1) because of the importance of atonal for the development of balance and hearing organs in Drosophila. The elevation of the Crh level in the Mecp2308 mice could explain the anxiety-like phenotype and the exaggerated poststress corticosterone response in these animals. 2016 Oct 25;5. pii: e19809. Huda Zoghbi 2011 Neuroscience Prize. Pehlivan first encountered some of these kids during his pediatric neurology rotation at the University of Istanbul School of Medicine in his native Turkey. Huda Yahya Zoghbi (geborene Huda El-Hibri; * 20. About Us. Lab Members . Master. Recognizing the importance of protein interactions for mediating SCA1 pathogenesis, and given that SCA1 shares clinical and pathological features with several other inherited ataxias, we proposed that understanding the interactions of Ataxin-1 as they relate to the interactions of proteins implicated in other ataxias might provide better insight about molecular mechanisms leading to Purkinje cell degeneration and ataxia. Even in her education, the war could have disrupted her path to where she is today. The finding that Mecp2308 mice have altered RNA-splicing patterns in the cerebral cortex that are significantly different from these of wild-type animals led us to propose that MeCP2 acts as repressor, but when it is released from the promoter region, it participates in its second function as a splicing regulator of the newly transcribed genes. Outdoors, the Lebanese civil war raged, making daily trips between home and lectures too dangerous. Third, we found that mutant Ataxin-1 has to be in its native complexes (that contain Capicua) to make its pathogenic affects. Publications . In addition we are performing genetic and biochemical studies to gain better insight about the in vivo function of the native Ataxin-1 complexes and the role of Capicua in the nervous system. Dr. Huda Zoghbi is the Ralph D. Feigin professor at Baylor College of Medicine, an investigator at the Howard Hughes Medical Institute, and the director of the Jan and Dan Duncan Neurological Research Institute at Texas Children’s Hospital. In the Lab. We are currently investigating several protein interactions within the network to gain better insight about SCA1 pathogenesis and the pathogenesis of other poly-glutamine diseases such as SCA6 and SCA7. In collaboration with the Orr lab, we found that residue S776 in Ataxin-1 is necessary for Ataxin-1's toxicity. Glutamine-expanded Ataxin-1 causes disease by a gain-of-function mechanism given that mice lacking this protein do not reproduce SCA1 features. © 2019 Huda Zoghbi Lab and Zhandong Liu Lab, Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital1250 Moursund St., Houston, TX We are collaborating with Nathaniel Heintz at Rockefeller University to isolate cell-specific RNAs using the BACarray technology developed in his lab. Huda Zoghbi’s experience diagnosing patients with Rett syndrome motivated her scientific research. We have begun to characterize patients with the duplication and found that some have Rett-like features, while others have autism spectrum phenotypes. She is also an investigator at the Howard Hughes Medical Institute and the director of the Jan and Dan Duncan Neurological Research Institute (NRI) at Texas Children's Hospital. Moreover, several of the direct physical interactors are modifiers of disease phenotypes in animal models. This led us to propose that duplications of MeCP2 might lead to postnatal neurologic disorders, which indeed is proving to be the case. Rotation Student. Although she initially trained to be a clinical pediatric neurologist, Huda Y. Zoghbi, MD, soon found herself drawn to research. Leben. Huda Zoghbi: A lab of her own October 20, 2014 October 7, 2016 Momentum 0 Comments Dr. Arthur Beaudet, Dr. Huda Zoghbi, Dr. Ralph Feigin, Education, Genetics, Howard Hughes Medical Institute Investigator, molecular and human genetics, Neuroscience, pediatrics, Research, Rett Syndrome, Vilcek Prize. We generated a mouse model by creating a mutation that truncates the protein post–amino acid 308. Baylor College of Medicine will be closed on Monday, Jan. 18 in observance of Martin Luther King, Jr. Day. To test this hypothesis we used proteins whose genes are mutated in various ataxias to develop a "phenotype-based" protein interaction network (ataxia interactome) in collaboration with Marc Vidal at the Dana-Farber Cancer Institute. The excessive MeCP2 protein made by the extra copy of the gene severely affects brain function. Fall 2019 (Oct-Dec) Lupita Rios . Call today to schedule an appointment or fill out an online request form. doi: 10.7554/eLife.19809. We are studying both the Mecp2308 and overexpression mice to identify the neuron-specific expression and splicing changes that result from MeCP2 dysfunction. Our functional and pathogenesis studies, revealed that MeCP2 interacts with the RNA-binding protein YB-1 and that this interaction affects alternative splicing of reporter cassettes regulated by YB-1. They also collaborate with labs studying Drosophila to study the function of proteins America's fourth largest city is a great place to live, work and play. Get in touch. In males, the inactivating mutations cause severe neonatal encephalopathy and death in infancy, whereas milder mutations may cause mental retardation, motor dysfunction, and psychosis. A new computational tool has been designed to make the life of bench scientists easier when it comes to identifying genes that are involved in particular diseases, an arduous and time consuming process. Her work helped elucidate mechanisms of Rett syndrome and spinocerebellar ataxia type 1. If requested before 2 p.m. you will receive a response today. Huda Zoghbi Lab Lab Members; Research Areas; Publications; Contact Us; Baylor College of Medicine; Research; Labs and Centers; Faculty Labs; Huda Zoghbi Lab; Research Areas; Navigation . This model predicts that most proteins that interact with wild-type Ataxin-1 should interact with the mutant protein and that modifications of Ataxin-1 that might alter its conformation are critical to pathogenesis. Huda Yahya Zoghbi (Arabic: هدى الهبري الزغبي Hudā al-Hibrī az-Zughbī; born 1954), born Huda El-Hibri, is a Lebanese-born American geneticist, and a professor at the Department of Molecular and Human Genetics, Baylor College of Medicine. Rotation Student. To determine the anatomical substrates for the various Rett phenotypes we are generating mice that lack MeCP2 in specific neurons. Male Mecp2308 mice appear normal up to six weeks of age, when they develop tremors, seizures, coordination problems, social behavior abnormalities, and forepaw stereotypies similar to the hand-wringing seen in patients. This led us to propose that protein misfolding or impaired protein clearance might be critical in SCA1 pathogenesis. We are continuing to characterize the Math1-null mice to pinpoint the neurons involved in the respiration phenotype, and we are pursuing the identification of Math1's downstream targets to define the molecular pathways involved in the differentiation of the diverse cell types dependent on Math1. Find out why.Get to Know Houston. „Dieses Projekt entstand aus einer Zusammenarbeit mit dem Labor von Dr. Huda Zoghbi, die Studien zu neurologischen Erkrankungen. Phone. Our efforts have focused on addressing how increasing the number of glutamines in Ataxin 1 causes neuronal degeneration. Huda Y. Zoghbi was born and raised in Beirut, Lebanon. 713–798–8728 . Addgene is a nonprofit plasmid repository dedicated to improving life science research. Fall 2019 (Oct-Dec) Nisha Gupta . Inside the Lab with Davut Pehlivan, MD. Learn more about research in the Huda Zoghbi Lab. Zoghbi studierte Biologie … In her career, Zoghbi faced many obstacles. Rotation Student. In 1999, we discovered that Rett syndrome is caused by mutations in the gene encoding methyl-CpG-binding protein 2 (MECP2). “I was encountering a lot of patients who had devastating neurological problems, and many of them were genetic,” she recalls. 1. Media Component. Importantly, from this model we learned that neurons that develop nuclear inclusions last are the most vulnerable. However, she would not allow it. The spinocerebellar ataxias (SCAs) are dominantly inherited neurodegenerative disorders characterized by a progressive loss of balance and coordination, and eventually the inability to coordinate swallowing and breathing. Dr. Huda Zoghbi mentoring a colleague in her lab. Fall (Aug-Oct) 2019. Huda Zoghbi: I was really intrigued by one thing about this syndrome — the girls are healthy and look healthy when they’re born and achieve certain milestones, and then they lose those acquired skills.And we know that it’s not degenerative because they can live into adulthood. This suggested to us that the nuclear inclusions are probably protective by sequestering the glutamine-expanded protein and reducing its native interactions. We found that 14-3-3 proteins interact with Ataxin-1 in a S776-dependent manner and that 14-3-3 augments levels of Ataxin-1 when phosphorylated at S776 by Akt kinase. Post Doc in Dr. Huda Zoghbi's lab : Carlos Orozco. Parameters-J Known Junctions data base in bed format.-G Genome model directory containing respective alternativ splicing, gene model and Junction database files.Data for DM3, MM9, MM10, HG19, HG38 are provided. These mice lack cerebellar granule neurons, pontine neurons, hair cells in the vestibular and auditory systems, and the D1 interneurons of the spinocerebellar tracts. Peggy Goodell (Stem Cells and Regenerative Medicine, Baylor College of Medicine) DNA methylation in normal and malignant hematopoiesis. Fox Photos/Getty Images. Years ago, the lab of Dr. Huda Zoghbi together with the lab of Dr. Harry Orr at University of Minnesota discovered that mutations that repeat a region of the gene lead to SCA1, a condition in which the cerebellum wastes away, typically leading to progressive deterioration of motor coordination and balance, and difficulties with swallowing and breathing. Start of Lecture 3 (00:11) From The Howard Hughes Medical Institute the 2003 Holiday Lectures on Science. For a few months during medical school, Huda Zoghbi slept in a windowless closet inside a women’s bathroom at the American University of Beirut. The laboratory uses genetic, biochemical, and cell biological approaches to explore the pathogenesis of polyglutamine neurodegenerative diseases and Rett syndrome, and to study genes essential for normal neurodevelopment. By Sharon Begley @sxbegle. “He loved learning, and he always pushed my sister and brothers and me to read,” Zoghbi recalls. 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