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Microdomains set the stage for breakthroughs in study of human disease

J. Andrew MacKay builds on his team’s attempt to control polypeptide-based structures

J. Andrew MacKay knows that the next big step to understanding and treating disease starts on an extremely small scale.

His research on microdomains — functional structures that are 10 to a thousand times smaller than a cell — at the USC School of Pharmacy has earned the assistant professor his first Research Project Grant from the National Institutes of Health.

“By using biological materials to assemble structures, process information and harness energy, the emerging field of synthetic biology may bridge the gap between current technology and that needed to study and intervene in disease,” MacKay said. “Working toward that goal, this project elaborates on a platform discovered by our team to control polypeptide-based microdomains.”

Cellular pathways

MacKay’s interdisciplinary team is the first to report that intracellular elastin-like-polypeptides generate microdomains that exert control over cellular pathways, and he hopes to be able to design microdomains for specific functions.

We envision microdomains as tools that turn ‘off’ or ‘on’ biological pathways.

J. Andrew MacKay

“Through design, we envision microdomains as tools that turn ‘off’ or ‘on’ biological pathways with high spatio-temporal control,” MacKay said.

“When completed, this project will deliver a biomolecular toolbox of broad utility to study biological processes associated with human disease,” he added.

The project’s co-principal investigators are Gavin S. Herbert Professor and Executive Vice Dean Sarah Hamm-Alvarez and Associate Professor Curtis Okamoto.

J. Andrew MacKay (Photo/Chris Jones)

J. Andrew MacKay (Photo/Chris Jones)

This grant represents the next phase of research for MacKay and his team, who have been developing polypeptide-based drug carriers that can be used in the treatment of cancer, ocular diseases and other human diseases.

“Our goal is to repackage drugs into bioresponsive nanocarriers, which activate site-specific drug release and reduce toxicity,” said MacKay, whose overall goal is to formulate and evaluate successful carrier strategies for clinical translation.

The NIH grant builds on MacKay’s previous funding, provided by the U.S. Army Telemedicine and Advanced Technology Research Center, the Stop Cancer Foundation, the American Cancer Society, the USC Research Center for Liver Disease, the USC Ming Hsieh Institute, the Whittier Foundation, the Wright Foundation, the Southern California-Clinical Translational Science Institute and the USC School of Pharmacy.

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Microdomains set the stage for breakthroughs in study of human disease

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