Healthy brain cells rely on tightly regulated RNA processing and turnover to maintain normal function. With aging, these processes become less efficient. This leads to the accumulation of aberrant RNA species—which researchers refer to as “RNA pollution.” The buildup of RNA pollution is associated with cellular stress and may contribute to an increased vulnerability to neurodegenerative diseases such as Alzheimer’s disease.
Anne Bang, PhD , associate professor in the Center for Therapeutics Discovery at Sanford Burnham Prebys Medical Discovery Institute and director of Cell Biology at the Conrad Prebys Center for Chemical Genomics , is part of an interdisciplinary team of scientists and physicians investigating this RNA pollution and developing strategies to reduce its accumulation.
Under the leadership of Gene Yeo, PhD , professor of cellular and molecular medicine at the University of California San Diego School of Medicine and director of the Center for RNA Technologies and Therapeutics, the group was awarded a $13 million grant from the California Institute for Regenerative Medicine (CIRM) to better understand this process and identify potential therapeutic approaches.
The researchers will convert patient-derived cells into neurons for study. This approach preserves key features of biological age and RNA state. It enables comparison of cells from healthy individuals and patients with neurodegenerative diseases.
Bang will use advanced robotics at the Conrad Prebys Center for Chemical Genomics at Sanford Burnham Prebys to test thousands of candidate compounds for their ability to reduce RNA pollution. The team will assess whether restoring RNA homeostasis improves cellular function, including in cells with genetic risk.
“Neurodegenerative diseases are difficult to treat because we lack models that capture early changes in aging neurons,” said Bang. “By pairing human cell models with scalable screening, we can identify strategies to restore normal RNA processing before damage becomes irreversible.”
Joining Yeo and Bang as co-principal investigators are:
“This collaboration brings together expertise across RNA biology, human neuron modeling and therapeutic discovery,” said Bang. “The support from CIRM enables this work at a scale that links mechanistic insight to the evaluation of potential therapeutic strategies in human-relevant systems.”