Chemists at the University of Houston are using breakthrough imaging techniques to reveal how copper imbalances in the body contribute to neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and ALS.
Although the root causes of these incurable diseases remain largely unknown and existing drugs only manage symptoms, researchers have long linked copper imbalances within neurons to severe neurological disorders. Tai Yen Chen, an associate professor of chemistry at the University of California, hopes to pinpoint malfunctioning cellular pathways, providing the foundational knowledge needed to develop future treatments and guide therapeutic strategies.
Over the past decade, Chen’s lab has secured more than $4 million to investigate how copper regulation supports healthy brain development. His latest funding came in the form of a $2.16 million grant from the National Institute of General Medicine, part of the National Institutes of Health.
This five-year grant renewal follows an approximately $1.9 million National Institute of General Medical Sciences grant awarded in 2019 that supported Chen’s initial findings on cellular copper homeostasis. The recently published nature communications, This discovery challenges long-held views about how the critical transport protein CTR1 functions and raises new questions about how copper regulation affects cell function and development.
We discovered that a protein called CTR1, which takes copper into cells, is much more dynamic than scientists previously thought. We found that when copper levels get too high, CTR1 changes its structure to reduce copper uptake. This appears to be an important mechanism cells use to maintain healthy copper levels. ”
Tai-Yen Chen, Associate Professor of Chemistry, University of Houston
The new grant will allow Chen’s team to investigate how this regulatory behavior of copper is related to signaling in human neurons and how disruption of this process contributes to neurodegenerative diseases.
Using advanced imaging tools developed in Chen’s lab, the team is able to observe and measure individual CTR1 protein complexes within individual cells. This allows researchers to see cell-by-cell differences and detect rare protein behaviors that might be hidden if only large groups of cells are measured at a time.
Traditional biochemical methods are powerful at measuring global trends, but typically report average signals from many cells and many proteins. This averaging can make it difficult to see small differences between individual cells, abnormal protein behavior, or short-term events that may be important in disease.
Chen’s single-molecule approach allows for a detailed look at how individual proteins behave in living cells, giving researchers a more detailed perspective on the regulation of copper. This approach could ultimately help scientists study other diseases and biological processes in which rare molecular events and differences between individual cells play important roles.
“Some neurological diseases have remained largely unanswered until now because there have been no effective approaches to answering these complex questions,” Chen said. “Our unique imaging approach allows us to ask new questions quantitatively, providing insights and advancing the field.”
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Reference magazines:
Wen, M.-H. others. (2025). Elevated intracellular copper induces CTR1 monomerization and prevents copper uptake. nature communications. DOI: 10.1038/s41467-025-66283-w. https://www.nature.com/articles/s41467-025-66283-w
