By: Grace Huff
This November, the Norman Fixel Institute for Neurological Diseases at UF Health is bringing awareness to Alzheimer’s disease and supporting the individuals and families affected by it as we recognize Alzheimer’s Awareness Month. In the depths of discovery lies a lab guided by curiosity, courage, and a little bit of genomic dark matter. This lab is led by Lien Nguyen, PhD, an assistant professor in Molecular Genetics and Microbiology. This team of scientists is asking the big questions about Alzheimer’s and challenging long-held assumptions along the way.
In 2022, Nguyen opened the Nguyen Lab, her independent research group at the University of Florida. Since then, she has centered her research around a bold hypothesis: hidden within the repetitive sequences of our genome, sometimes dismissed as “junk DNA,” may lie the key to understanding and eventually confronting neurodegenerative diseases.
Her lab does extensive work around tandem repeats and repeat expansions. These are stretches of DNA that copy themselves in long chains. These repetitive elements make up more than half of our genome, yet their roles in health and disease remain largely unknown.
Nguyen’s team pursues three intertwined aims:
- Detecting novel repeat expansions in patients by screening for pathological signatures, such as accumulation of RAN proteins or RNA foci, in tissue samples and then leveraging sequencing, enrichment, and computational tools.
- Deciphering the pathogenic impact of these newly discovered expansions by creating new model systems, including animal models and patient-derived cell cultures, to test how these repeats might drive disease processes.
- Exploring native functions of tandem repeats within the central nervous system to see how these sequences might regulate brain-specific gene expression, respond to stress, or impact neuronal health.
One of the more recent breakthroughs from the Nguyen lab is especially relevant to Alzheimer’s disease. In 2025, Nguyen and her colleagues published a finding of an intronic expansion in CASP8 that appears in brain tissue from Alzheimer’s patients. This produces poly-glycine-arginine (polyGR) aggregates, an unexpected pathology, and is statistically enriched in Alzheimer’s cases. “Our research uncovered a hidden genetic change that may help explain why some people develop Alzheimer’s. Each new finding like this brings us closer to answers, and to better treatments in the future,” said Nguyen. In other words, the team found a slight change in a gene, CASP8, which appears more frequently in people with Alzheimer’s. This change causes specific proteins to clump together in the brain, something the researchers did not expect to find. These clumps may play a role in how Alzheimer’s develops and can help scientists uncover new ways to treat or prevent the disease.
This work is especially hopeful due to its bridge between molecular genetics and human disease. Nguyen’s group is directly mining human patient samples for hidden repeat extensions, then bringing those discoveries into models to test whether they truly alter one’s neuronal fate. Over time, the goal is to uncover any new risk factors for Alzheimer’s, open new therapeutic avenues, and ultimately move closer to interventions that can slow, stop, or prevent the disease.
Alzheimer’s awareness month gives us a moment to reflect on the many lives affected by this neurodegenerative disease. The Nguyen lab reminds us that even the darkest corners of our genome may hold the clues we need and that bold science can shine a light there.