Nancy Bonini

Bonini was born in 1959 to parents Rose and William “Bill” Bonini.{{cite web |url=https://www.amacad.org/sites/default/files/media/document/2019-06/electionIndex2000-2018.pdf |title=Members of the American Academy Listed by election year, 2000–2018 |author= |date=2019 |website=amacad.org |publisher=American Academy of Arts and Sciences |access-date=1 Aug 2019 }} Her father was a Professor of GeoScience and Civil Engineering at Princeton University from 1952 to 1996.{{cite news |last=Kelly|first=Morgan|title=Geoscientist William Bonini, dedicated teacher and genial colleague, dies at 90 |url=https://www.princeton.edu/news/2017/01/03/geoscientist-william-bonini-dedicated-teacher-and-genial-colleague-dies-90 |work= Princeton University News|location=Princeton, NJ, USA |date=3 Jan 2017 |access-date= 12 Jul 2019}} Nancy, her sister (Jennifer), brothers (Jack and Jamie), and father all attended Princeton University.{{cite web |url=http://www.centraljersey.com/obituaries/william-e-bill-bonini/article_ba240da6-ce02-11e6-96ee-0f19b2830b1d.html |title=William E. "Bill" Bonini, 90 |author= |date=29 Dec 2016 |website=www.centraljersey.com |publisher=Packet Media, LLC |access-date= 12 Jul 2019}}

Bonini earned an AB degree from Princeton University in 1981, studying Biology.{{cite web |url=https://www.princeton.edu/paw/archive_old/PAW98-99/16-0609/0609cns.html |title=A fly like thee. Studying the fruit fly, Nancy Bonini '81 unravels causes of neurodegenerative diseases |last=Nichols|first=Peter|date=1999 |website=www.princeton.edu |publisher=Princeton University |access-date=18 Jul 2019 }} 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".{{cite journal |last1=Tempel |first1=Bruce L. |last2=Bonini |first2=Nancy|last3=Dawson |first3=Douglas R.|last4=Quinn |first4=William G. |date=1983 |title=Reward learning in normal and mutant Drosophila |journal=Proceedings of the National Academy of Sciences of the United States of America |volume=80 |issue=5 |pages=1482–1486 |doi= 10.1073/pnas.80.5.1482|pmid=6572401 |pmc=393622 |bibcode=1983PNAS...80.1482T |doi-access=free }} 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,{{cite magazine |author= |title= From the Labs: Dave Nelson Lab|url=https://biochem.wisc.edu/sites/default/files/About_Us/newsletters/2010BiochemNewsletter.pdf |magazine=University of Wisconsin-Madison Biochemistry Newsletter |location=Wisconsin, USA |date= 2010|access-date=11 Aug 2019 }} graduating with a Doctorate (Ph.D.) in Neuroscience in 1987.{{cite web |url=https://ntp.neuroscience.wisc.edu/alumni/ |title= Neuroscience Training Program – Alumni|author= |date= 2019|website=www.ntp.neuroscience.wisc.edu |publisher=University of Wisconsin – Madison |access-date=18 Jul 2019 }} Bonini's post-doctoral research was performed in the laboratory of Seymour Benzer (behavioral geneticist) at the California Institute of Technology. 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.{{cite journal |last1=Warrick |first1= John M|last2=Paulson |first2=Henry L|authorlink2= Henry L. Paulson|last3=Gray-Board|first3=Gladys|last4=Fischbeck|first4=Kenneth H|last5=Pittman|first5=Randall N|last6=Bonini |first6=Nancy M. |date=12 Jun 1998 |title=Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila |journal= Cell|volume=93 |issue=6 |pages= 939–949|doi= 10.1016/S0092-8674(00)81200-3|pmid= 9635424|s2cid= 17720790|doi-access=free}}{{cite journal |author=Max Perutz |date= 1 Feb 1999|title= Glutamine repeats and neurodegenerative diseases: molecular aspects. |journal=Trends in Biochemical Sciences |volume= 24|issue= 2|pages=58–63 |doi= 10.1016/S0968-0004(98)01350-4|pmid= 10098399|author-link= Max Perutz}}

In 1998, Bonini's research conclusively demonstrated that Drosophila could be used as an in vivo model for human neurodegenerative disease. Using this model, Bonini's research group subsequently discovered unexpected and novel pathways that play a role in normal biology, injury, and disease. 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.{{cite book|author1=R. Horowski|author2=Y. Mizuno|author3=C.W. Olanow|author4=W. Poewe|author5=P. Riederer|authorlink5=Peter Riederer|author6=J.A. Stoessel|author7=M.B.H. Youdim| authorlink7= Moussa B. H. Youdim|title=Advances in Research on Neurodegeneration |url=https://books.google.com/books?id=m2xu68gysMkC&pg=PA62|access-date=20 July 2019|date=24 July 2003|publisher=Springer Science & Business Media|isbn=978-3-211-83907-2|pages=52–}}{{cite journal |last1=Warrick |first1= JM|last2= Chan|first2=HY|last3=Gray-Board|first3=GL|last4=Paulson|first4=H|last5=Bonini|first5=NM |date=1999 |title=Suppression of polyglutamine disease in Drosophila by the molecular chaperone hsp70 |journal=Nature Genetics |volume=23 |issue= 4|pages=425–428 |doi= 10.1038/70532|pmid= 10581028|s2cid= 24632055}}

Studying Polyglutamine repeat diseases (polyQ diseases) in Drosophila neurodegeneration models, Bonini's research group elucidated an important role for molecular chaperones in polyQ diseases,{{cite journal |last1=Chai |first1=Y |last2=Koppenhafer |first2=SL|last3=Bonini| first3=NM|last4=Paulson |first4=HL |date=1 Dec 1999 |title= Analysis of the role of heat shock protein (Hsp) molecular chaperones in polyglutamine disease|journal=The Journal of Neuroscience |volume=19 |issue= 23|pages= 10338–47|doi= 10.1523/JNEUROSCI.19-23-10338.1999|pmid=10575031 |pmc=6782415 }} and subsequently Parkinson's disease.{{cite journal |last1=Helfand |first1=Stephen L. |date=1 Feb 2002 |title= Chaperones Take Flight|journal=Science |volume=295 |issue=5556 |pages=809–810 |doi= 10.1126/science.1069544|pmid=11823628 |s2cid=84002211 }} 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.{{cite book|author1=R. Horowski|author2=Y. Mizuno|author3=C.W. Olanow|author4=W. Poewe|author5= P. Riederer|author6=J.A. Stoessel|author7=M.B.H. Youdim|title=Advances in Research on Neurodegeneration |chapter-url=https://books.google.com/books?id=m2xu68gysMkC&pg=PA62|access-date=20 July 2019|date=24 July 2003|publisher=Springer Science & Business Media|isbn=978-3-211-83907-2|page=117|chapter=General Aspects of Neurodegeration}} 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.{{cite web |url= https://penntoday.upenn.edu/news/drug-averts-parkinsons-disease-fruit-flies-suggesting-new-approaches-human-neurodegenerative-di|title=Drug Averts Parkinson's Disease in Fruit Flies, Suggesting New Approaches to Human Neurodegenerative Diseases |author= |date=11 Nov 2002 |website=www.penntoday.upenn.edu |publisher=University of Pennsylvania |access-date=22 Jul 2019 }}

Bonini's research laboratory developed and validated a Drosophila model for familial ALS,{{cite journal |date=5 Sep 2008 |title= A Fly Model for ALS|url=http://www.jbc.org/content/283/36/e99948.full|journal= Journal of Biological Chemistry|volume= 283|pages=e99948 |doi= 10.1016/S0021-9258(19)49256-9|doi-access= free}}{{cite web |url=https://www.hhmi.org/bulletin/february-2011/hope-floats |title=Hope Floats: With a new arsenal of robust models of ALS, drug development may move to the fast track. |first=Brian|last=Varslag|date= Feb 2011|website= www.hhmi.org|publisher=Howard Hughes Medical Institute |access-date=21 Jul 2019 |quote=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."}} 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.{{cite news |first=Faye|last=Flam |authorlink= Faye Flam|title= Researchers at University of Pennsylvania find possible genetic link to Lou Gehrig's disease|url=https://www.inquirer.com/philly/health/20100826_Researchers_at_University_of_Pennsylvania_find_possible_genetic_link_to_Lou_Gehrig_s_disease.html |work=The Philadelphia Inquirer |date=26 Aug 2010 |access-date=16 Jul 2019 }}{{cite journal |last1= Elden|first1= Andrew C.|last2= Kim|first2= Hyung-Jun|last3= Hart|first3= Michael P.|last4= Chen-Plotkin|first4= Alice S.|last5= Johnson|first5= Brian S.|last6= Fang|first6= Xiaodong|last7= Armakola|first7= Maria|last8= Geser|first8= Felix|last9= Greene|first9= Robert|last10= Lu|first10= Min Min|last11= Padmanabhan|first11= Arun|last12= Clay-Falcone|first12= Dana|last13= McCluskey|first13= Leo|last14= Elman|first14= Lauren|last15= Juhr|first15= Denise|last16= Gruber|first16= Peter J.|last17= Rüb|first17= Udo|last18= Auburger|first18= Georg|last19= Trojanowski|first19= John Q.|last20= Lee|first20= Virginia M.-Y.|last21= Van Deerlin|first21= Vivianna M.|last22= Bonini|first22= Nancy M.|last23= Gitler|first23= Aaron D.|title= Ataxin-2 intermediate-length polyglutamine expansions are associated with increased risk for ALS|journal=Nature |volume=466 |issue= 7310|pages=1069–1078 |doi=10.1038/nature09320 |pmid= 20740007|pmc= 2965417|year= 2010|bibcode= 2010Natur.466.1069E}}{{cite patent |country= USA|number= US20110142789A1 |status= |title= Compositions and Methods for the Diagnosis and Treatment of Amyotrophic Lateral Sclerosis |pubdate= |gdate= |fdate= |pridate= |inventor= |invent1=Aaron D. Gitler |invent2=Nancy M. Bonini |assign1=University of Pennsylvania |url= https://patents.google.com/patent/US20110142789A1/en?oq=12%2f965%2c618 }}{{cite journal |author2=Don W. Cleveland |author1=Clotilde Lagier-Tourenne|author2-link=Don W. Cleveland|date=25 Aug 2010 |title= An expansion in ALS genetics|journal=Nature |volume=466 |issue= 7310|pages=1052–1053 |doi= 10.1038/4661052a|pmid=20740002|s2cid=205056924|quote=”… 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.|doi-access=free}}

The Bonini lab discovered that a conserved microRNA, miR-34, plays a neuroprotective role in the brains of aging Drosophila.{{cite journal |last1=Aw |first1=Sherry |last2=Cohen |first2=Stephen M. |date=Aug 2012 |title= Time is of the essence: microRNAs and age-associated neurodegeneration |url= |journal=Nature |volume= 22|issue= 8|pages=1218–1220 |doi=10.1038/cr.2012.59 |pmid=22491478 |pmc=3411169 }} 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.{{cite web |url=https://www.alzforum.org/news/research-news/neurodegeneration-and-aging-could-microrna-be-link |title=Neurodegeneration and Aging: Could MicroRNA Be the Link? |author=Gwyneth Dickey Zakaib |date=17 Feb 2012 |website=www.alzforum.org |access-date=21 Feb 2019 }}

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.{{cite journal |last1=Nativio |first1= Raffaella|last2=Donahue |first2=Greg|last3=Berson| first3=Amit|last4=Lan|first4=Yemin|last5=Amlie-Wolf|first5=Alexandre|last6=Tuzer |first6=Ferit|last7=Toledo|first7 =Jon B.|last8=Gosai|first8=Sager J.|last9=Gregory|first9=Brian D.|last10=Torres|first10=Claudio|last11=Trojanowski|first11=John Q.|last12=Wang|first12=Li-San|last13=Johnson|first13=F.Brad|last14=Bonini|first14=nancy M.|last15=Berger|first15=Shelley L. |authorlink15= Shelley Berger|date= 2018|title=Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease |journal=Nature Neuroscience |volume=21 |issue= 4|pages=497–505 |doi= 10.1038/s41593-018-0101-9|pmid= 29507413|pmc= 6124498|doi-access=free}}

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), an Investigator of the Howard Hughes Medical Institute (2000–2013), and the Florence RC Murray Professor of Biology (2012-). In 2012, she was elected to the National Academy of Sciences,{{cite web |url=http://www.nasonline.org/news-and-multimedia/news/2012_05_01_NAS_Election.html |title=National Academy of Sciences Members and Foreign Associates Elected|author= |date=1 May 2012 |website=www.nasonline.org |publisher= National Academy of Sciences|access-date= 20 Jul 2019}} and the National Academy of Medicine.{{cite news |url=https://www.asbmb.org/uploadedFiles/ASBMBToday/Content/Archive/ASBMBToday-2012-12.pdf |title= ASBMB Today|author= |date=1 Dec 2012 |publisher=American Society for Biochemistry and Molecular Biology |access-date=15 Jul 2019 |location= USA}} Also in 2012, Bonini became an elected Fellow of the American Association for the Advancement of Science.{{cite web |url=https://www.aaas.org/news/aaas-members-elected-fellows-2 |title= AAAS Members Elected as Fellows|author= |date=Dec 2011 |website=aaas.org |publisher=American Association for the Advancement of Science |access-date=20 Jul 2019 }} In 2014, Bonini was elected to the American Academy of Arts and Sciences.{{cite web |author= |title= Ellison Medical Foundation Senior Scholar Nancy Bonini elected to American Academy of Arts and Sciences |url= https://www.ellisonfoundation.org/node/4919 |website= ellisonfoundation.org |date= 2014|access-date=15 Jul 2019 }}

Bonini was the recipient of a March of Dimes Basil O'Connor Award in 1996,{{cite journal |title=Molecular Analysis of Drosophila eyes absent Mutants Reveals Features of the Conserved Eya Domain |url=https://www.genetics.org/content/155/2/709 |journal=Genetics |year=2000 |volume=155 |issue=2 |pages=709–720 |pmid=10835393 |access-date= 26 Jul 2019|last1=Bui |first1=Q. T. |last2=Zimmerman |first2=J. E. |last3=Liu |first3=H. |last4=Bonini |first4=N. M. |doi=10.1093/genetics/155.2.709 |pmc=1461105 }} a Packard Fellowship for Science and Engineering in 1997,{{cite web |url=https://www.packard.org/what-we-fund/science/packard-fellowships-for-science-and-engineering/fellowship-directory/bonini-nancy-m/ |title=Nancy M. Bonini, 1997 Fellow |author= |date=2019 |website=www.packard.org |publisher=David and Lucile Packard Foundation |access-date=26 Jul 2019 }} an Ellison Medical Foundation Senior Scholar in Aging Research Award in 2009,{{cite web |url= http://www.ellisonfoundation.org/awardlist/aging-senior-scholar/2009|title= 2009 Senior Scholar Award in Aging|author= |date=2009 |website= www.ellisonfoundation.org|publisher=Ellison Medical Foundation |access-date=20 Jul 2019 }} a Glenn Award for Research in the Biological Mechanisms of Aging in 2015,{{cite web |url=https://glennfoundation.org/awards-programs/glenn-awards/ |title= Glenn Foundation for Medical Research: Award Recipients|author= |date=2019 |website=www.glennfoundation.org |publisher= Glen Foundation|access-date=20 Jul 2019 }} and a National Institutes of Health Outstanding Investigator R35 Award in 2016.{{cite web |url=https://www.ninds.nih.gov/Funding/About-Funding/Research-Program-Award-R35/NINDS-Research-Program-Award-R35-Recipients-FY-2017 |archive-date=21 March 2019|archive-url=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|title=NINDS Research Program Award (R35) Recipients FY 2017 |author= |date=28 Jun 2018 |website= www.ninds.nih.gov|publisher=National Institutes of Health|access-date= 20 Jul 2019}}{{cite web |url=https://www.nih.gov/news-events/news-releases/nih-initiates-pilot-grant-program-innovative-neurological-research |title=NIH initiates pilot grant program for innovative neurological research |author= |date= 26 Jan 2017|website=www.nih.gov |publisher=National Institutes of Health|access-date=20 Jul 2019 }} In 2010, she appeared as a panelist on Charlie Rose’s The Brain Series (Episode: The Disordered Brain).{{cite AV media |people=Charlie Rose (talk show), Eric Kandel, John Donoghue (neuroscientist), John Krakauer, Nancy Bonini |date=22 Jul 2010 |title= The Disordered Brain |medium=video |language=en |url=https://charlierose.com/collections/3/clip/20518 |access-date=21 Jul 2019 |quote= 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. }}

File:Anthony R Cashmore Biochemist and Plant Molecular Biologist 2010 (cropped).jpg

Bonini is married to Anthony Cashmore, a University of Pennsylvania Professor Emeritus best known for discovering the cryptochrome that serves as a blue light photoreceptor in Arabidopsis.{{cite journal |last1=Nair |first1=Prashant |date=11 Jan 2011|title= Profile of Anthony R. Cashmore |journal=Proceedings of the National Academy of Sciences |volume=108 |issue=2 |pages=443–445 |doi= 10.1073/pnas.1018069108|pmid=21191100 |pmc=3021040 |bibcode=2011PNAS..108..443N |doi-access=free }}

• Warrick JM, Paulson HL, Gray-Board GL, Bui QT, Fischbeck KH, Pittman RN, Bonini NM (1998) Expanded Polyglutamine Protein Forms Nuclear Inclusions and Causes Neural Degeneration in Drosophila. Cell 93(6): 939–949. {{PMID| 9635424}}.
• 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: 425–428. {{PMID|10581028}}.
• Auluck PK, Chan HY, Trojanowski JQ, Lee VM, Bonini NM (2002) Chaperone suppression of alpha-synuclein toxicity in a Drosophila model for Parkinson's disease. Science 295(5556):865-8. {{PMID| 11823645}}
• Watson MR, Lagow RD, Xu K, Zhang B, Bonini NM (2008) A Drosophila Model for Amyotrophic Lateral Sclerosis Reveals Motor Neuron Damage by Human SOD1. Journal of Biological Chemistry 283:24972-24981. {{PMID|18596033}}. (highlighted as paper of the week)
• Kim HJ, Raphael AR, LaDow ES, McGurk L, Weber RA, Trojanowski JQ, Lee VM, Finkbeiner S, Gitler AD, Bonini NM (2014) Therapeutic modulation of eIF2α phosphorylation rescues TDP-43 toxicity in amyotrophic lateral sclerosis disease models. Nature Genetics 46:152-160. {{PMID|24336168}}.
• Nativio R, Donahue G, Berson A, Lan Y, Amlie-Wolf A, Tuzer F, Toledo JB, Gosai SJ, Gregory BD, Torres C, Trojanowski JQ, Wang LS, Johnson FB, Bonini NM, Berger SL (2018) Dysregulation of the epigenetic landscape of normal aging in Alzheimer's disease. Nature Neuroscience 21: 497–505. {{PMID|29507413}}.

• McGurk L, Berson A, Bonini NM (2015) Drosophila as an in vivo model for human neurodegenerative disease. Genetics 201: 377–402. {{PMID|26447127}}.
• Fang Y, Bonini NM (2015) Hope on the (fruit) fly—the Drosophila wing paradigm of axon injury. Neural Regeneration Research 10: 173–5. {{PMID|25883604}}.
• McGurk L, Rifai O, Bonini NM (2019) Poly(ADP-ribosylation) in age-related neurological disease. Trends in Genetics 35: 601–613. {{PMID|31182245}}.

• Bonini NM, Hardiman O (2015) Ataxin-2 expands insight into the ALS clinical spectrum. Neurology 84: 244–5. {{PMID|25527266}}.
• Bonini NM, Berger SL (2017) The Sustained Impact of Model Organisms–in Genetics & Epigenetics. Genetics 205:1-4. {{PMID|28049700}}.

{{reflist}}

• [http://web.sas.upenn.edu/bonini-lab/ Official website-The Bonini Lab]
• {{google scholar id|RGN7eWwAAAAJ}}

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{{DEFAULTSORT:Bonini, Nancy}}

Category:American neuroscientists

Category:American women neuroscientists

Category:American women geneticists

Category:American geneticists

Category:Howard Hughes Medical Investigators

Category:Fellows of the American Academy of Arts and Sciences

Category:Fellows of the American Association for the Advancement of Science

Category:Princeton University alumni

Category:University of Wisconsin–Madison alumni

Category:1959 births

Category:Living people

Category:University of Pennsylvania faculty

Category:University of Pennsylvania Department of Biology faculty

Category:Members of the United States National Academy of Sciences

Category:American women academics

Category:Annual Reviews (publisher) editors

Category:21st-century American women

Category:Members of the National Academy of Medicine