URIs_MOMENTUM_Research_and_Innovation_Magazine_Fall_2024_Mel

ENVIRONMENTAL EXPOSURE AND REPROGRAMMING THE BRAIN LEADING TO ALZHEIMER’S DISEASE

Written by NICOLE MARANHAS

As an early leader in brain epigenetics (the study of how, when, and why combinations of genes are turned on and off to make proteins), Nasser Zawia, University of Rhode Island (URI) professor of biomedical and pharmaceutical sciences and Ryan research professor of neuroscience, was among the first to show a potential link between childhood lead exposure and the development of Alzheimer’s disease. “If your brain cells are impacted during this critical window of development, it can permanently reprogram gene expression,” Zawia says. “Once your neurons develop, they mostly stay with you for a lifetime.” His work has helped pave the way for the understanding of how environmental toxins— particularly in poorer communities—can lead to later disease. Chemical pollutants, such as perfluorooctanesulfonic acid (PFOS) once used in stain repellants, remain present in many household products. Zawia worked on a study with URI pharmacy Professor Angela Slitt on the role of PFOS in late-onset Alzheimer’s disease. “These ‘forever’ chemicals enter your body and stay there a very long time,” says Zawia. “We are finding that they have an impact on neuromuscular function and biomarkers of Alzheimer’s disease, ADHD, and autism.” Zawia will serve as consultant on a new grant at Boston University to study the role of metallic toxins in Alzheimer’s disease and related disorders. His research has also helped shed light at gene-level changes that may precede Alzheimer’s disease. Recently, Zawia looked at the potential to repurpose an anti-inflammatory drug to “turn off” Alzheimer’s disease at the gene level. “Many therapies target Alzheimer’s disease at its end stages,” explains Zawia. “I’m interested to see how we can intervene with the gene machinery before the pathology starts.”

This device was developed jointly by the Manuel and Quinlan labs. It is used to measure joint stiffness in an animal model of Cerebral Palsy.

The Ryan Institute has brought in more than $45 million in federal and private funding in the past five years to research neurodegenerative diseases.

NASSER ZAWIA Professor

Biomedical and Pharmaceutical Sciences Ryan Research Professor of Neuroscience

studies whether the LINC complex is involved in the heightened risk of Alzheimer’s disease for people after ischemic stroke, which blocks blood flow to the brain. “Studies have shown that risk of Alzheimer’s disease can double after ischemic stroke,” she says. “One of our questions is to look at whether changes we see in the pathways affected by the LINC complex after stroke make surviving brain cells more vulnerable to factors linked to Alzheimer’s disease or age-related stressors.” The Institute’s overall vision, however, is what truly grounds Fallini. “Sometimes people get lost in the details of the mechanisms and lose track of the purpose of why this work matters,” she says. “I was drawn to the Ryan Institute because of the therapeutic focus. For ALS, I want to try to help people who have no cure, no therapeutics, nothing to improve quality of life or their survival. Am I doing work that is meaningful to them? That is the question that drives me.”

That same mindset drives not just the Ryan Institute and its faculty, but URI’s overall prioritization of neuroscience. URI’s Interdisciplinary Neuroscience Program (INP) offers undergraduate and graduate degrees on multiple neuroscience tracks—cementing the University’s status as a regional biomedical science hub. The program began with three students in the first semester and has now expanded to include more than 150 students. Many URI neuroscience faculty and students collaborate with nearby biotech, pharmaceutical, and clinical entities in Rhode Island and Massachusetts, as well as medical and academic institutions across the U.S. and overseas. The Ryan Institute has brought in more than $45 million in federal and private funding in the past five years to research neurodegenerative diseases. However, those funds cannot be used for buildings. The partnerships forged by the leadership of the Ryan institute between academia, industry, and government are crucial to our collective success. The research being conducted by this team will resonate in the lives of people for decades to come.

Zawia was among the first to show a potential link between childhood lead exposure and the development of Alzheimer’s disease.

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