Nancy Bonini

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), Alzheimer's disease, and Parkinson's disease, as well as aging, neural injury and regeneration, and response to environmental toxins.

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 (since 2012). She was editor of the Annual Review of Genetics from 2018-2021.

Bonini was born in 1959 to parents Rose and William E. Bonini. Her father was a Professor of GeoScience and Civil Engineering at Princeton University from 1952 to 1996. Raised in Princeton, New Jersey, she graduated from Princeton Day School in 1977. Nancy, her sister (Jennifer), brothers (Jack and Jamie), and father all attended Princeton University.

Bonini earned an AB degree from Princeton University in 1981, studying biology. 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". 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, graduating with a Doctorate (Ph.D.) in Neuroscience in 1987. Bonini's postdoctoral 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.

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.

Studying Polyglutamine repeat diseases (polyQ diseases) in Drosophila neurodegeneration models, Bonini's research group elucidated an important role for molecular chaperones in polyQ diseases, and subsequently Parkinson's disease. 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. 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.

Bonini's research laboratory developed and validated a Drosophila model for familial ALS, 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.

The Bonini lab discovered that a conserved microRNA, miR-34, plays a neuroprotective role in the brains of aging Drosophila. 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.