To Rid Body of Asthma and COPD, UMD Researchers Hack Into Mucus Protein

For most people, the common cold causes sniffles and maybe a run to the drugstore. For Colin Savage ’26, who grew up with asthma, even a mild infection might overwhelm his lungs with so much mucus that he could hardly breathe, prompting his parents to rush him to the emergency room. 

Now the University of Maryland biochemistry major is part of a team of UMD faculty and students developing a scientific method to help the 28 million Americans like him with the disease, by engineering molecules to identify and destroy the protein responsible for excess mucus secretion. 

Normally that protein protects the respiratory system from foreign invaders, but for people suffering from chronic respiratory diseases, the body produces too many, plugging up the airway with phlegm. If successful, the research could lead to therapeutics that wipe out asthma, COPD and even COVID. 

The project—funded with a UMD Grand Challenges Grant—unites researchers with UMD’s College of Computer, Mathematical, and Natural Sciences; A. James Clark School of Engineering; and First-Year Innovation and Research Experience (FIRE), which provides undergraduates with a faculty-mentored research experience.

Savage’s FIRE group is testing synthetic DNA that can home in on a mucus protein like a missile. Eventually, it hopes to load these nucleotides with an enzyme “warhead” engineered to obliterate the protein.

Despite his personal stake in the issue, Savage joined the project serendipitously, after enrolling in FIRE as a freshman and taking on an Alzheimer’s disease project. When Catherine Spirito, a FIRE associate clinical professor and assistant director who leads FIRE’s molecular diagnostics program, collaborated on the Grand Challenges Grant with colleagues the following year, she recruited Savage and others onto the mucus project, offering the chance for students to collaborate with researchers across campus and in a private lab.

“I thought it would help them fit their research into a broader picture and see how it can be utilized in different applications,” said Spirito.

For biochemistry major Zackary Shpilman ’26, “There was more opportunity to get to a meaningful conclusion in an experiment and make a large-scale impact in therapeutics,” he said.

Among other things, Spirito’s lab searches for and identifies synthetic aptamers: unique sequences of DNA or RNA whose folds allow them to target and bind to proteins. For the mucus project, she purchased a DNA library, which is a collection of trillions of different DNA sequences or potential aptamer candidates. For the past year her team has introduced them to mucus proteins to see which ones stick—literally. After several rounds, the team has identified a pool of aptamer candidates that appear to bind more strongly. The next step is sequencing and testing to see which arrangements work best.

The Grand Challenges mucus team also includes bioengineering Associate Professor Gregg Duncan, who runs a lab pursuing pulmonary disease applications. He recently published a breakthrough study in Gene Therapy demonstrating that it is possible to selectively block the mucus-producing gene MUC5AC, which drives excess phlegm, while sparing more benign proteins involved in normal secretions—a feat he achieved by applying a gene-silencing technique to lab-grown lung tissue. (It was Duncan’s discovery that allowed Spirito’s lab to test its aptamers.) A potential therapeutic could eliminate MUC5AC while leaving the other protein untouched, Duncan’s study showed.

Like Savage, Duncan grew up with asthma, reliant on inhalers and steroids to manage symptoms. The experience drove him to research respiratory diseases and, ultimately, mucus proteins.

“I thought, ‘Well, if the protein is what's really causing the issues in severe asthma, then why don't we try to treat that selectively, versus generally?’” said Duncan, whose research is funded by the National Institutes of Health in addition to the Grand Challenges Grant. 

The mucus team is led by cell biology and molecular genetics Associate Professor Louisa Wu and joined by Philip Bryan, the founder and scientific director of the Potomac Affinity Proteins lab in North Potomac, Md. Bryan engineered the enzyme that specifically kills MUC5AC—the “warhead” that Spirito’s group hopes to affix to the right aptamer. 

In previous experiments Duncan has used Bryan’s enzyme to destroy MUC5AC in combination with protein-binding antibodies, rather than aptamers. Aptamers, however, are cheaper to engineer than antibodies, motivating Savage during his final year on the project.

“I came to molecular diagnostics to make health care more accessible to people without fancy or expensive instruments,” he said. “I wanted to meet them where they’re at.”