Nancy Bonini Explained

Nancy M. Bonini
Nationality:American
Workplaces:University of Pennsylvania
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Doctoral Advisor:David L. Nelson
Known For:Developed the first Drosophila model of human neurodenerative disease
Spouse:Anthony Cashmore
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Website:http://web.sas.upenn.edu/bonini-lab/

Nancy M. Bonini (born 1959) is an American neuroscientist and geneticist, best known for pioneering the use of Drosophila as a model organism to study neurodegeneration of the human brain. Using the Drosophila model approach, Bonini's laboratory has identified genes and pathways that are important in the development and progression of neurodegenerative diseases such as Amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's Disease),[1] Alzheimer's disease,[2] and Parkinson's disease,[3] [4] as well as aging, neural injury and regeneration,[5] and response to environmental toxins.[4]

A professor of biology at the University of Pennsylvania since 1994, Bonini has held appointments as the inaugural Lucille B. Williams Term Professor of Biology (2006–2012),[6] an Investigator of the Howard Hughes Medical Institute (2000–2013),[7] [8] and the Florence RC Murray Professor of Biology (since 2012).[9] She was editor of the Annual Review of Genetics from 2018-2021.[10] [11]

Early life and education

Bonini was born in 1959 to parents Rose and William “Bill” Bonini.[12] Her father was a Professor of GeoScience and Civil Engineering at Princeton University from 1952 to 1996.[13] Nancy, her sister (Jennifer), brothers (Jack and Jamie), and father all attended Princeton University.[14]

Bonini earned an AB degree from Princeton University in 1981, studying Biology.[15] Her undergraduate thesis research, performed under the direction of William (Chip) Quinn, formed the basis for her first publication, "Reward Learning in Normal and Mutant Drosophila".[16] After graduation, Bonini entered the Neurosciences Training Program at the University of Wisconsin–Madison. There, she completed doctoral research in the laboratory of David L. Nelson,[17] graduating with a Doctorate (Ph.D.) in Neuroscience in 1987.[18] Bonini's post-doctoral research was performed in the laboratory of Seymour Benzer (behavioral geneticist) at the California Institute of Technology.[15] Focusing on using the fruit fly as a tool for understanding the genetic basis of the brain and behavior, Bonini was the first to demonstrate that Drosophila can be used as a model of human neurodegenerative disease.[19] [20]

Research

The fruit fly as a model for human neurodegenerative disease

In 1998, Bonini's research conclusively demonstrated that Drosophila could be used as an in vivo model for human neurodegenerative disease.[19] [20] Using this model, Bonini's research group subsequently discovered unexpected and novel pathways that play a role in normal biology, injury, and disease.[15] In the pioneering study that showed that the fruit fly can be used as a model of disease, Bonini's laboratory collaborated with human geneticists to examine the effects of expressing normal and mutant forms of a human neurodegenerative polyQ disease protein. Flies that expressed the mutant form of the protein showed symptoms and characteristics similar to those seen in human polyQ disease patients; flies that expressed the normal protein did not.[21] [22]

Chaperones and Polyglutamine Repeat Diseases

Studying Polyglutamine repeat diseases (polyQ diseases) in Drosophila neurodegeneration models, Bonini's research group elucidated an important role for molecular chaperones in polyQ diseases,[23] and subsequently Parkinson's disease.[3] [21] [24] In those studies, upregulation of the chaperone Hsp70 suppressed neurodegeneration, and this finding established chaperones as a new therapeutic target for Parkinson's disease and other neurodegenerative disorders.[3] [24] [25] Bonini's research team demonstrated the pharmacologic potential of chaperones in further Drosophila studies; administering geldanamycin (an antitumor antibiotic that acts on Hsp90) to mutant flies before symptoms of neural decline were visible averted the onset of neurodegeneration in the mutant flies, suggesting a new approach for people susceptible to Parkinson's disease and other neurodegenerative conditions.[26]

Amyotrophic lateral sclerosis (ALS/Lou Gehrig's Disease)

Bonini's research laboratory developed and validated a Drosophila model for familial ALS,[5] [27] [28] then used an ALS model to evaluate genes and pathways important for ALS onset, progression, and possible treatment. Through these studies, Bonini's team, in collaboration with Aaron Gitler, discovered that ATXN2 (the gene that encodes the protein Ataxin-2) was a disease susceptibility gene for ALS, and that interrupting the interaction between TDP-43 and Ataxin-2 was a promising target for treating ALS and other diseases.[28] [29] [30] [31] [32]

A role for brain microRNAs in aging and disease

The Bonini lab discovered that a conserved microRNA, miR-34, plays a neuroprotective role in the brains of aging Drosophila.[33] The loss of miR-34 resulted in a profile consistent with accelerated aging, late-onset brain neurodegeneration, and reduced survival, whereas upregulation of miR-34 enhanced survival and mitigated neurodegeneration.[33] [34]

An epigenetic basis for Alzheimer's disease

In 2018, Bonini, with collaborators Shelley Berger, Brad Johnson, and others, completed a study investigating the epigenetic landscape of tissue samples donated by individuals who did and did not have Alzheimer's disease. The findings established the basis for an epigenetic link between aging and Alzheimer's disease, suggesting a new model for the disease and a paradigm shift from the previously established view of Alzheimer's disease as an 'advanced state of normal aging'. Based on the study findings, Bonini and collaborators established that a set of normal aging changes that occur in the epigenome protect against Alzheimer's disease, and that disrupting those normal protective changes may be a trigger that predisposes people to the disease.[2] [35]

Honors and awards

A professor of biology at the University of Pennsylvania since 1994, Bonini has held appointments as the inaugural Lucille B. Williams Term Professor of Biology (2006–2012),[6] an Investigator of the Howard Hughes Medical Institute (2000–2013),[7] [8] and the Florence RC Murray Professor of Biology (2012-).[9] In 2012, she was elected to the National Academy of Sciences,[8] [36] and the National Academy of Medicine.[37] Also in 2012, Bonini became an elected Fellow of the American Association for the Advancement of Science.[38] In 2014, Bonini was elected to the American Academy of Arts and Sciences.[39]

Bonini was the recipient of a March of Dimes Basil O'Connor Award in 1996,[40] a Packard Fellowship for Science and Engineering in 1997,[41] an Ellison Medical Foundation Senior Scholar in Aging Research Award in 2009,[42] a Glenn Award for Research in the Biological Mechanisms of Aging in 2015,[43] and a National Institutes of Health Outstanding Investigator R35 Award in 2016.[44] [45] In 2010, she appeared as a panelist on Charlie Rose’s The Brain Series (Episode: The Disordered Brain).[46]

Personal

Bonini is married to Anthony Cashmore,[14] a University of Pennsylvania Professor Emeritus best known for discovering the cryptochrome that serves as a blue light photoreceptor in Arabidopsis.[47]

Representative publications

Journal articles

Reviews

Commentary

External links

Notes and References

  1. Web site: DC: New ALS Genetics Hog the Limelight at Satellite Conference . . 2011. www.alzforum.org . FBRI LLC . 21 Jul 2019 .
  2. News: . Penn Study Shows that the "Epigenetic Landscape" is Protective in Normal Aging, Impaired in Alzheimer's Disease . Penn Medicine News . USA . 5 Mar 2018 . 19 Jul 2019 .
  3. Whitworth . Alexander . Wes . Paul D. . Pallanck. Leo J.. 2006. Drosophila models pioneer a new approach to drug discovery for Parkinson's disease . . 11 . 3/4 . 119– . 10.1016/S1359-6446(05)03693-7. 16533709 . 20 Jul 2019 .
  4. Web site: Drosophila Define DJ-1's Defensive Role . . 16 Dec 2005 . www.alzforum.org . FBRI LLC . 21 Jul 2019 .
  5. Disease Models and Mechanisms. Berrack. Ugur. Kuchuan. Chen. Hugo J.. Bellen. Drosophila tools and assays for the study of human diseases . 2016. 9. 3. 235–244 . 10.1242/dmm.023762. 26935102. 4833332. 21 Jul 2019. The recently developed Drosophila wing injury assay is an elegant approach to study axonal degeneration and regeneration in vivo (Fang et al., 2012). The goal of these studies is to identify genes that are required for axonal degeneration and regeneration, and to identify the regulatory processes that are involved in spinal cord and nerve injuries. .
  6. Web site: Science Professors to Four Chairs . . 1 May 2007 . www.almanac.upenn.edu . University of Pennsylvania. 20 Jul 2019 .
  7. Web site: Our Investigators: Nancy M. Bonini, PhD . . 2019 . hhmi.org . . 15 Jul 2019 .
  8. Web site: HHMI Scientists Elected to National Academy of Sciences in 2012. . 1 May 2012 . www.hhmi.org . .
  9. Web site: Dr. Nancy Bonini appointed as the Florence R.C. Murray Professor of Biology . . 8 Aug 2012 . www.bio.upenn.edu . . 20 Jul 2019 .
  10. Web site: EDITOR OF THE ANNUAL REVIEW OF GENETICS - VOLUME 52, 2018 . Annual Reviews . 29 July 2021.
  11. Web site: EDITOR OF THE ANNUAL REVIEW OF GENETICS - VOLUME 55, 2021 . 9 February 2022. Annual Reviews.
  12. Web site: Members of the American Academy Listed by election year, 2000–2018 . . 2019 . amacad.org . . 1 Aug 2019 .
  13. News: Kelly. Morgan. Geoscientist William Bonini, dedicated teacher and genial colleague, dies at 90 . Princeton University News. Princeton, NJ, USA . 3 Jan 2017 . 12 Jul 2019.
  14. Web site: William E. "Bill" Bonini, 90 . . 29 Dec 2016 . www.centraljersey.com . Packet Media, LLC . 12 Jul 2019.
  15. Web site: A fly like thee. Studying the fruit fly, Nancy Bonini '81 unravels causes of neurodegenerative diseases . Nichols. Peter. 1999 . www.princeton.edu . . 18 Jul 2019 .
  16. Tempel . Bruce L. . Bonini . Nancy. Dawson . Douglas R.. Quinn . William G. . 1983 . Reward learning in normal and mutant Drosophila . . 80 . 5 . 1482–1486 . 10.1073/pnas.80.5.1482. 6572401 . 393622 . 1983PNAS...80.1482T . free .
  17. . From the Labs: Dave Nelson Lab. University of Wisconsin-Madison Biochemistry Newsletter . Wisconsin, USA . 2010. 11 Aug 2019 .
  18. Web site: Neuroscience Training Program – Alumni. . 2019. www.ntp.neuroscience.wisc.edu . . 18 Jul 2019 .
  19. Warrick . John M. Paulson . Henry L. Gray-Board. Gladys. Fischbeck. Kenneth H. Pittman. Randall N. Bonini . Nancy M. . 12 Jun 1998 . Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila . Cell. 93 . 6 . 939–949. 10.1016/S0092-8674(00)81200-3. 9635424. 17720790. free.
  20. Max Perutz . 1 Feb 1999. Glutamine repeats and neurodegenerative diseases: molecular aspects. . Trends in Biochemical Sciences . 24. 2. 58–63 . 10.1016/S0968-0004(98)01350-4. 10098399. Max Perutz.
  21. Book: R. Horowski. Y. Mizuno. C.W. Olanow. W. Poewe. P. Riederer. J.A. Stoessel. M.B.H. Youdim. Advances in Research on Neurodegeneration . 20 July 2019. 24 July 2003. Springer Science & Business Media. 978-3-211-83907-2. 52–.
  22. Warrick . JM. Chan. HY. Gray-Board. GL. Paulson. H. Bonini. NM . 1999 . Suppression of polyglutamine disease in Drosophila by the molecular chaperone hsp70 . Nature Genetics . 23 . 4. 425–428 . 10.1038/70532. 10581028. 24632055.
  23. Chai . Y . Koppenhafer . SL. Bonini. NM. Paulson . HL . 1 Dec 1999 . Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease. . 19 . 23. 10338–47. 10.1523/JNEUROSCI.19-23-10338.1999. 10575031 . 6782415 .
  24. Helfand . Stephen L. . 1 Feb 2002 . Chaperones Take Flight. . 295 . 5556 . 809–810 . 10.1126/science.1069544. 11823628 . 84002211 .
  25. Book: R. Horowski. Y. Mizuno. C.W. Olanow. W. Poewe. P. Riederer. J.A. Stoessel. M.B.H. Youdim. Advances in Research on Neurodegeneration . https://books.google.com/books?id=m2xu68gysMkC&pg=PA62. 20 July 2019. 24 July 2003. Springer Science & Business Media. 978-3-211-83907-2. 117. General Aspects of Neurodegeration.
  26. Web site: Drug Averts Parkinson's Disease in Fruit Flies, Suggesting New Approaches to Human Neurodegenerative Diseases . . 11 Nov 2002 . www.penntoday.upenn.edu . . 22 Jul 2019 .
  27. 5 Sep 2008 . A Fly Model for ALS. Journal of Biological Chemistry. 283. e99948 . 10.1016/S0021-9258(19)49256-9. free.
  28. Web site: Hope Floats: With a new arsenal of robust models of ALS, drug development may move to the fast track. . Brian. Varslag. Feb 2011. www.hhmi.org. . 21 Jul 2019 . In 1998, however, Bonini authored an idea that radically extended the scientific reach of the humble insect. She mused that inserting genes related to human brain diseases might yield critical insights into poorly understood neurodegenerative conditions, including Huntington's disease, Parkinson's disease, and ALS. "I saw it as, 'there are all these terrible diseases and nobody is really studying them in model organisms,'" Bonini says. "I knew it was a high-risk thing.".
  29. News: Faye. Flam . Researchers at University of Pennsylvania find possible genetic link to Lou Gehrig's disease. . 26 Aug 2010 . 16 Jul 2019 .
  30. Elden. Andrew C.. Kim. Hyung-Jun. Hart. Michael P.. Chen-Plotkin. Alice S.. Johnson. Brian S.. Fang. Xiaodong. Armakola. Maria. Geser. Felix. Greene. Robert. Lu. Min Min. Padmanabhan. Arun. Clay-Falcone. Dana. McCluskey. Leo. Elman. Lauren. Juhr. Denise. Gruber. Peter J.. Rüb. Udo. Auburger. Georg. Trojanowski. John Q.. Lee. Virginia M.-Y.. Van Deerlin. Vivianna M.. Bonini. Nancy M.. Gitler. Aaron D.. Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS. . 466 . 7310. 1069–1078 . 10.1038/nature09320 . 20740007. 2965417. 2010. 2010Natur.466.1069E.
  31. USA. US20110142789A1 . Compositions and Methods for the Diagnosis and Treatment of Amyotrophic Lateral Sclerosis . Aaron D. Gitler . Nancy M. Bonini . .
  32. Don W. Cleveland . Clotilde Lagier-Tourenne. Don W. Cleveland. 25 Aug 2010 . An expansion in ALS genetics. . 466 . 7310. 1052–1053 . 10.1038/4661052a. 20740002. 205056924. ”… present evidence on page 1069 of this issue that short expansions of glutamine (Q) amino-acid residues — a polyglutamine, or polyQ tract — in the ataxin-2 protein are associated with increased risk of ALS. This unexpected finding comes 15 years after the discovery that long polyQ expansions in ataxin-2 cause spinocerebellar ataxia type 2, a neurodegenerative disorder involving abnormalities of gait.. free.
  33. Aw . Sherry . Cohen . Stephen M. . Aug 2012 . Time is of the essence: microRNAs and age-associated neurodegeneration . . 22. 8. 1218–1220 . 10.1038/cr.2012.59 . 22491478 . 3411169 .
  34. Web site: Neurodegeneration and Aging: Could MicroRNA Be the Link? . Gwyneth Dickey Zakaib . 17 Feb 2012 . www.alzforum.org . 21 Feb 2019 .
  35. Nativio . Raffaella. Donahue . Greg. Berson. Amit. Lan. Yemin. Amlie-Wolf. Alexandre. Tuzer . Ferit. Toledo. Jon B.. Gosai. Sager J.. Gregory. Brian D.. Torres. Claudio. Trojanowski. John Q.. Wang. Li-San. Johnson. F.Brad. Bonini. nancy M.. Berger. Shelley L. . 2018. Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease . . 21 . 4. 497–505 . 10.1038/s41593-018-0101-9. 29507413. 6124498. free.
  36. Web site: National Academy of Sciences Members and Foreign Associates Elected. . 1 May 2012 . www.nasonline.org . National Academy of Sciences. 20 Jul 2019.
  37. News: ASBMB Today. . 1 Dec 2012 . . 15 Jul 2019 . USA.
  38. Web site: AAAS Members Elected as Fellows. . Dec 2011 . aaas.org . . 20 Jul 2019 .
  39. Web site: . Ellison Medical Foundation Senior Scholar Nancy Bonini elected to American Academy of Arts and Sciences . ellisonfoundation.org . 2014. 15 Jul 2019 .
  40. Molecular Analysis of Drosophila eyes absent Mutants Reveals Features of the Conserved Eya Domain . Genetics . 2000 . 155 . 2 . 709–720 . 10835393 . 26 Jul 2019. Bui . Q. T. . Zimmerman . J. E. . Liu . H. . Bonini . N. M. . 10.1093/genetics/155.2.709 . 1461105 .
  41. Web site: Nancy M. Bonini, 1997 Fellow . . 2019 . www.packard.org . . 26 Jul 2019 .
  42. Web site: 2009 Senior Scholar Award in Aging. . 2009 . www.ellisonfoundation.org. . 20 Jul 2019 .
  43. Web site: Glenn Foundation for Medical Research: Award Recipients. . 2019 . www.glennfoundation.org . Glen Foundation. 20 Jul 2019 .
  44. Web site: NINDS Research Program Award (R35) Recipients FY 2017 . 21 March 2019. https://web.archive.org/web/20190321093115/https://www.ninds.nih.gov/Funding/About-Funding/Research-Program-Award-R35/NINDS-Research-Program-Award-R35-Recipients-FY-2017. . 28 Jun 2018 . www.ninds.nih.gov. National Institutes of Health. 20 Jul 2019.
  45. Web site: NIH initiates pilot grant program for innovative neurological research . . 26 Jan 2017. www.nih.gov . National Institutes of Health. 20 Jul 2019 .
  46. Charlie Rose (talk show), Eric Kandel, John Donoghue (neuroscientist), John Krakauer, Nancy Bonini . 22 Jul 2010 . The Disordered Brain . video . en . 21 Jul 2019 . As part of Charlie's Brain Series, a panel of experts gives insight into disorders of the brain, such as Parkinson's disease, stroke, and paralysis, and describes the latest cutting-edge treatments. .
  47. Nair . Prashant . 11 Jan 2011. Profile of Anthony R. Cashmore . . 108 . 2 . 443–445 . 10.1073/pnas.1018069108. 21191100 . 3021040 . 2011PNAS..108..443N . free .

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