“Huda Zoghbi”的意思、由来-开放百科全书

Huda Yahya Zoghbi (Arabic: هدى الهبري الزغبي Hudā al-Hibrī az-Zughbī; born 1954), born Huda El-Hibri,^[2] is a Lebanese-born American geneticist, and a professor at the Department of Molecular and Human Genetics, Baylor College of Medicine.^[5] Her work helped elucidate mechanisms of Rett syndrome and spinocerebellar ataxia type 1. In 2017, she was awarded the Canada Gairdner International Award and the Breakthrough Prize in Life Sciences.

Early life and education

Huda Zoghbi was born in Beirut, Lebanon in 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. Her mother convinced her to study biology instead, on the grounds that 'a woman growing up in the Middle East should pick a career ensuring independence and security, while she can always write on the side'.^[6]^[7] 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.^[7]

The Lebanese Civil War began in 1976 during her first year of medical school. Although she and her classmates decided to stay at the university, after her brother was injured by shrapnel, their parents sent them to live with their sister in Austin, Texas, with plans to return the following summer.^[7]^[8] 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 began 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.^[8] Despite her continued desire to return to Lebanon the next summer, on the advice of professors at AUB, she stayed at Meharry and earned an MD degree in 1979, after which she joined the Texas Children's Hospital at the Baylor College of Medicine as a pediatric resident.^[7]

Zoghbi initially intended to specialise in pediatric cardiology, out of an interest in the heart. During her rotation at pediatric neurology, Marvin Fishman, the head of the division, convinced her that the brain was more interesting than the heart. She thus started a 3-year term as a postdoctoral researcher in pediatric neurology after she finished her residency in 1982.

Career

From 1982 to 1985, Zoghbi was a postdoctoral researcher in pediatric neurology at the Baylor College of Medicine. She became an assistant professor at the Department of Pediatrics at Baylor in 1988, and was successively promoted to associate professor in 1991 and professor in 1994.^[9] At present, Zoghbi is primarily 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.^[5] She is also a member of the board of directors of Regeneron.^[3]

Research

In 1983, Zoghbi learnt of Rett syndrome from Bengt Hagberg's account in Annals of Neurology. The paper allowed Zoghbi to diagnose a five-year-old she treated at Texas Children's Hospital, and a week later she saw another patient with the same set of symptoms. When she investigated medical records, she found more cases of Rett syndrome that had been misdiagnosed. This sparked her interest in Rett syndrome, at a time when there was no report of the disease in the US.^[2] An article she published in 1985^[10] attracted many Rett syndrome patients to Texas Children's Hospital, giving her access to a large number of cases.^[11]

Since most patients of Rett syndrome were girls, and symptoms were very consistent across patients, Zoghbi believed genetics were involved in the disease process.^[2] This led her to join Arthur Beaudet's group in 1985, after finishing her term as a postdoctoral researcher, for training in genetics and molecular biology.^[8] Beaudet advised against Rett syndrome as her research project since its mode of inheritance was still not obvious, and recommended a more approachable problem - spinocerebellar ataxia type 1, a dominantly inherited neurological disorder. In 1988, Zoghbi left Beaudet's group and founded her own lab at Baylor.^[7]

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.^[8] They determined that the disease was caused by an expansion of the glutamine-encoding CAG trinucleotide repeat in this gene, and that the younger the age of onset, the longer the CAG repeat.^[12] 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.^[13]

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, Zoghbi chose to study its mammalian homolog. A member of her lab successfully cloned the mouse homolog, Math1, in 1996.^[14] Her team went on to find that, in addition to its involvement in balance and coordination, Math1 is also crucial to hearing ^[15] and the formation of secretory cells in the gut.^[16] 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.^[17]

Rett syndrome

Ever since 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.^[18] In 1999, a postdoctoral researcher in Zoghbi's lab identified MECP2 as the causative gene.^[19] The MECP2 protein binds methylated cytosine (5-methylcytosine) in CpG sites, and is indispensable for almost all brain cells.^[8] In the paper, she and her team demonstrated that Rett syndrome was an X-linked dominant disorder, meaning that when 1 of the 2 copies of the MECP2 gene is abnormal, Rett syndrome will result.^[6]

Zoghbi's team keeps studying MECP2, and discovered in 2004 that overexpressing the protein in mouse led to an autism-like neurological disorder.^[20] In 2009, she found mice deficient of the Mecp2 gene (the mouse homolog of human MECP2) had lower levels of norepinephrine, dopamine and serotonin,^[21] 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,^[22] and that restoring the level of MECP2 protein in a subset of neurons was sufficient to rescue some symptoms of Rett syndrome.^[23]

Awards and honors

Personal life

Zoghbi met her husband, William Zoghbi when they were medical students in the American University of Beirut. In 1977, she continued her medical school study in Meharry Medical College, and William transferred to Meharry next year. They both had their residencies in the Baylor College of Medicine after graduation. They married in 1980 and have 2 children.^[4] William is the chief of the Department of Cardiology at Houston Methodist Hospital.^[37]

References

1. ^{{cite news|author1=Cha, Ariana Eunjung|title=Silicon Valley’s ‘Nobels’: Mega-prizes awarded for work in brains, the origins of life and gravitational waves|url=https://www.washingtonpost.com/news/to-your-health/wp/2016/12/04/silicon-valleys-nobels-mega-prizes-awarded-for-work-in-brains-the-origins-of-life-and-gravitational-waves/?noredirect=on&utm_term=.c6a46eaa69fb|accessdate=13 Dec 2018|work=Washington Post|date=4 Dec 2016|archiveurl=https://web.archive.org/web/20181115140237/https://www.washingtonpost.com/news/to-your-health/wp/2016/12/04/silicon-valleys-nobels-mega-prizes-awarded-for-work-in-brains-the-origins-of-life-and-gravitational-waves/?noredirect=on&utm_term=.f3ec22731f3a|archivedate=15 Oct 2018}}
2. ^¹²³{{cite magazine|last=Azvolinsky|first=Anna|date=1 Nov 2018|title=Genetic Neurologist: A Profile of Huda Zoghbi|url=https://www.the-scientist.com/profile/genetic-neurologist--a-profile-of-huda-zoghbi-64943|magazine=|location=|publisher=The Scientist|accessdate=13 Dec 2018}}
3. ^¹{{cite web|title=Huda Y. Zoghbi, M.D.|url=https://investor.regeneron.com/board-directors/huda-zoghbi|publisher=Regeneron|accessdate=13 Dec 2018}}
4. ^¹{{cite web|author=Zoghbi, Huda Y.|title=Autobiography of Huda Y Zoghbi|url=http://www.shawprize.org/en/shaw.php?tmp=3&twoid=102&threeid=255&fourid=475&fiveid=233|publisher=Shaw Prize Foundation|accessdate=13 Dec 2018|date=27 Sep 2016}}
5. ^¹²³⁴⁵⁶{{cite web|title=Huda Yahya Zoghbi, M.D.|url=https://www.bcm.edu/people/view/huda-zoghbi-m-d/genetics-research-faculty-u-z/b1855108-ffed-11e2-be68-080027880ca6/53710912-91bc-42a4-9400-2d630a1612dc|publisher=Baylor College of Medicine|accessdate=13 Dec 2018}}
6. ^¹{{cite news|author1=Ellen, Elliot|title=Women in science: Huda Zoghbi discovered the genetic basis of Rett syndrome|url=https://www.jax.org/news-and-insights/jax-blog/2018/march/women-in-science-huda-zoghbi-autism|accessdate=13 Dec 2018|publisher=Jackson Laboratory|date=12 Mar 2018}}
7. ^¹²³⁴{{cite journal|author1=Nuzzo, Regina|title=Profile of Huda Y. Zoghbi|journal=Proceedings of the National Academy of Sciences of the United States of America|date=28 Feb 2006|volume=103|issue=9|pages=3017–3019|doi=10.1073/pnas.0509604103|pmid=16492741|pmc=1413894}}
8. ^¹²³⁴{{cite journal|author1=Neill, Ushma S.|title=A conversation with Huda Zoghbi|journal=Journal of Clinical Investigation|date=1 Mar 2016|volume=126|issue=3|pages=797–798|doi=10.1172/JCI86445|pmid=26928032|pmc=4767342}}
9. ^{{cite web|title=Biographical Notes of Laureates|url=http://www.shawprize.org/en/shaw.php?tmp=3&twoid=102&threeid=255&fourid=472|publisher=Shaw Prize Foundation|accessdate=13 Dec 2018|date=31 May 2016}}
10. ^{{cite journal|author1=Zoghbi, Huda Y.|author2=Percy, Alan K.|author3=Glaze, Daniel G.|author4=Butler, Ian J.|author5=Riccardi, Vincent M.|title=Reduction of Biogenic Amine Levels in the Rett Syndrome|journal=New England Journal of Medicine|date=10 Oct 1985|volume=33|issue=15|pages=921–924|doi=10.1056/NEJM198510103131504|pmid=2412119}}
11. ^{{cite interview|last=Zoghbi|first=Huda|subject-link=Huda Zoghbi|interviewer=McMullen Darra|title=Interview with Huda Zoghbi|url=https://digitalcommons.library.tmc.edu/cgi/viewcontent.cgi?article=1017&context=tmc-whp|publisher=Texas Medical Center Women's History Project|location=|date=9 Feb 2016|work=|access-date=13 Dec 2018}}
12. ^{{cite journal|author1=Orr, Harry T.|author2=Chung, Ming-yi|author3=Banfi, Sandro|author4=Kwiatkowski Jr., Thomas J.|author5=Servadio, Antonio|author6=Beaudet, Arthur L.|author7=McCall, Alanna E.|author8=Duvick, Lisa A.|author9=Ranum, Laura P. W.|author10=Zoghbi, Huda Y.|title=Expansion of an unstable trinucleotide CAG repeat in spinocerebellar ataxia type 1|journal=Nature Genetics|date=1 Jul 1993|volume=4|issue=3|pages=221–226|doi=10.1038/ng0793-221|pmid=8358429}}
13. ^{{cite journal|author1=Cummings, Christopher J.|author2=Mancini, Michael A.|author3=Antalffy, Barbara|author4=DeFranco, Donald B.|author5=Orr, Harry T.|author6=Zoghbi, Huda Y.|title=Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1|journal=Nature Genetics|date=1 Jun 1998|volume=19|issue=2|pages=148–154|doi=10.1038/502|pmid=9620770}}
14. ^{{cite journal|author1=Ben-Arie, Nissim|author2=McCall, Alanna E.|author3=Berkman, Scott|author4=Eichele, Gregor|author5=Bellen, Hugo J.|author6=Zoghbi, Huda Y.|title=Evolutionary conservation of sequence and expression of the bHLH protein Atonal suggests a conserved role in neurogenesis|journal=Human Molecular Genetics|date=1 Sep 1996|volume=5|issue=9|pages=1207–1216|doi=10.1093/hmg/5.9.1207|pmid=8872459}}
15. ^{{cite journal|author1=Bermingham, Nessan A.|author2=Hassan, Bassem A.|author3=Price, Steven D.|author4=Vollrath, Melissa A.|author5=Ben-Arie, Nissim|author6=Eatock, Ruth A.|author7=Bellen, Hugo J.|author8=Lysakowski, Anna|author9=Zoghbi, Huda Y.|title=Math1: An Essential Gene for the Generation of Inner Ear Hair Cells|journal=Science|date=11 Jun 1999|volume=284|issue=5421|pages=1837–1841|doi=10.1126/science.284.5421.1837|pmid=10364557}}
16. ^{{cite journal|author1=Yang, Qi|author2=Bermingham, Nessan A.|author3=Finegold, Milton J.|author4=Zoghbi, Huda Y.|title=Requirement of Math1 for secretory cell lineage commitment in the mouse intestine|journal=Science|date=7 Dec 2001|volume=294|issue=5549|pages=2155–2158|doi=10.1126/science.1065718|pmid=11739954}}
17. ^{{cite journal|last1=Flora|first1=Adriano|last2=Klisch|first2=Tiemo J.|last3=Schuster|first3=Gabriele|last4=Zoghbi|first4=Huda Y.|title=Deletion of Atoh1 Disrupts Sonic Hedgehog Signaling in the Developing Cerebellum and Prevents Medulloblastoma|journal=Science|date=4 Dec 2009|volume=326|issue=5958|pages=1424–1427|doi=10.1126/science.1181453|pmid=19965762|pmc=3638077}}
18. ^{{cite journal|author1=Ellison, Kimberley A.|author2=Fill, Carolyn P.|author3=Terwilliger, Joseph|author4=DeGennaro, Louis J.|author5=Martin-Gallardo, Antonia|author6=Anvret, Maria|author7=Percy, Alan K.|author8=Ott, Jurg|author9=Zoghbi, Huda Y.|title=Examination of X chromosome markers in Rett syndrome: exclusion mapping with a novel variation on multilocus linkage analysis|journal=American Journal of Human Genetics|date=Feb 1992|volume=50|issue=2|pages=278–287|pmid=1734712|pmc=1682446}}
19. ^{{cite journal|author1=Amir, Ruthie E.|author2=Van den Veyver, Ignatia B.|author3=Wan, Mimi|author4=Tran, Charles Q.|author5=Francke, Uta|author6=Zoghbi, Huda Y.|title=Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2|journal=Nature Genetics|date=1 Oct 1999|volume=23|issue=2|pages=185–188|doi=10.1038/13810|pmid=10508514}}
20. ^{{cite journal|author1=Collins, Ann L.|author2=Levenson, Jonathan M.|author3=Vilaythong, Alexander P.|author4=Richman, Ronald|author5=Armstrong, Dawna L.|author6=Noebels, Jeffrey L.|author7=Sweatt, J. David|author8=Zoghbi, Huda Y.|title=Mild overexpression of MeCP2 causes a progressive neurological disorder in mice|journal=Human Molecular Genetics|date=6 Sep 2004|volume=13|issue=21|pages=2679–2689|doi=10.1093/hmg/ddh282|pmid=15351775}}
21. ^{{cite journal|author1=Samaco, Rodney C.|author2=Mandel-Brehm, Caleigh|author3=Chao, Hsiao-Tuan|author4=Ward, Christopher S.|author5=Fyffe-Maricich, Sharyl L.|author6=Ren, Jun|author7=Hyland, Keith |author8=Thaller, Christina |author9=Maricich, Stephen M.|author10=Humphreys, Peter |author11=Greer, John J.|author12=Percy, Alan|author13=Glaze, Daniel G.|author14=Zoghbi, Huda Y.|author15=Neul, Jeffrey L.|title=Loss of MeCP2 in aminergic neurons causes cell-autonomous defects in neurotransmitter synthesis and specific behavioral abnormalities|journal=Proceedings of the National Academy of Sciences of the United States of America|date=22 Dec 2009|volume=106|issue=51|pages=21966–21971|doi=10.1073/pnas.0912257106|pmid=20007372|pmc=2799790}}
22. ^{{cite journal|author1=Chen, Lin|author2=Chen, Kaifu|author3=Lavery, Laura A.|author4=Baker, Steven A.|author5=Shaw, Chad A.|author6=Li, Wei|author7=Zoghbi, Huda Y.|title=MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome|journal=Proceedings of the National Academy of Sciences of the United States of America|date=28 Apr 2015|volume=112|issue=17|pages=5509–5514|doi=10.1073/pnas.1505909112|pmid=25870282|pmc=4418849}}
23. ^{{cite journal|author1=Ure, Kerstin|author2=Lu, Hui|author3=Wang, Wei|author4=Ito-Ishida, Aya|author5=Wu, Zhenyu|author6=He, Ling-jie|author7=Sztainberg, Yehezkel|author8=Chen, Wu|author9=Tang, Jianrong|author10=Zoghbi, Huda Y.|title=Restoration of Mecp2 expression in GABAergic neurons is sufficient to rescue multiple disease features in a mouse model of Rett syndrome|journal=eLife|date=21 Jun 2016|volume=5|pages=e14198|doi=10.7554/eLife.14198|pmid=27328321|pmc=4946897}}
24. ^{{cite web|title=Dr. Huda Y. Zoghbi|url=https://www.amacad.org/content/system/search.aspx?t=50&s=zoghbi|publisher=American Academy of Arts and Sciences|accessdate=14 Dec 2018}}
25. ^{{cite press release|last=|first=|date=8 Mar 2018|title=Molecular Medicine awards Ross Prize to Baylor College of Medicine’s Huda Zoghbi|url=https://www.feinsteininstitute.org/2018/03/molecular-medicine-awards-ross-prize-to-baylor-college-of-medicines-huda-zoghbi/|location=|publisher=Feinstein Institute for Medical Research|agency=|access-date=14 Dec 2018}}
26. ^{{cite news|title=Dr. Huda Zoghbi receives Lebanon's highest honor|url=https://nri.texaschildrens.org/news/dr-huda-zoghbi-receives-lebanons-highest-honor|accessdate=14 Dec 2018|publisher=Jan and Dan Duncan Neurological Research Institute|date=23 Jan 2018}}
27. ^{{cite web|title=Breakthrough Prize Life Sciences Laureates 2017|url=https://breakthroughprize.org/Laureates/2/P1/Y2017|publisher=Break Prize Foundation|accessdate=14 Dec 2018}}
28. ^{{cite web|title=Huda Y Zoghbi|url=https://gairdner.org/winners/index-of-winners/?_sfm_winner_type=Canada%20Gairdner%20International%20Award&_sfm_winner_year=1959+2020#Huda_Y_Zoghbi|publisher=Gairdner Foundation|accessdate=14 Dec 2018}}
29. ^{{cite web|title=Jessie Stevenson Kovalenko Medal|url=http://www.nasonline.org/programs/awards/kovalenko-medal.html|publisher=National Academy of Sciences|accessdate=14 Dec 2018}}
30. ^¹{{cite web|title=Huda Yahya Zoghbi|url=https://profiles.viictr.org/display/267945|publisher=Virtually Integrated Institutions for Clinical and Translational Research|accessdate=14 Dec 2018}}
31. ^{{cite news|title=Yale awards 12 honorary degrees at 2014 graduation|url=https://news.yale.edu/2014/05/19/yale-awards-12-honorary-degrees-2014-graduation|accessdate=14 Dec 2018|publisher=Yale University|date=19 May 2014}}
32. ^{{cite news|last1=Jennings|first1=Charles|title=McGovern Institute to honor neurogenetics researcher Huda Zoghbi|url=http://mcgovern.mit.edu/news/news/mcgovern-institute-to-honor-neurogenetics-researcher-huda-zoghbi/|accessdate=14 Dec 2018|publisher=McGovern Institute for Brain Research|date=4 Mar 2014}}
33. ^{{cite news|title=Texas Children's Hospital Neuroscientist Dr. Huda Zoghbi Receives 2011 Legacy Award from The Brookwood Community|url=https://www.texaschildrens.org/about-us/news/releases/texas-childrens-hospital-neuroscientist-dr-huda-zoghbi-receives-2011-legacy|accessdate=14 Dec 2018|publisher=Texas Children's Hospital}}
34. ^{{cite web|url=http://www.udem.edu.mx/Eng/VIAC/Pages/DICSA/catedra-laboris.aspx|title=Cathedra Laboris|publisher=University of Monterrey|access-date=September 12, 2017}}
35. ^{{cite news|title=Baylor College scientist wins Perl-UNC Neuroscience Prize|url=http://www.med.unc.edu/www/newsarchive/2008/may/baylor-college-scientist-wins-perl-unc-neuroscience-prize|accessdate=14 Dec 2018|publisher=University of North Carolina at Chapel Hill|date=20 May 2008}}
36. ^{{cite news|title=Arab Students' Organization hosts awards|url=http://news.mit.edu/2007/arab-sci-tech|accessdate=3 Dec 2018|publisher=Massachusetts Institute of Technology|date=12 Apr 2007}}
37. ^{{cite web|title=William A. Zoghbi, MD, FASE, FAHA, MACC|url=https://www.houstonmethodist.org/faculty/william-zoghbi/|publisher=Houston Methodist Hospital|accessdate=14 Dec 2018}}