Michael J. Holtzman, MD, has received close to $7.5 million in total funding for research aimed at developing stem cell-based treatments for chronic obstructive pulmonary disease (COPD), asthma, and other disorders.
Holtzman’s research at Washington University School of Medicine in St. Louis identified a subset of stem cells — cells that are able to grow into other more specialized types of cells — that line the airways and help drive mucus production in the lungs.
“Stem cells that give rise to mucus cells lining the airway and other sites are part of our immune defense strategy,” Holtzman, the director of the Division of Pulmonary and Critical Care Medicine, said in a university press release written by Julia Evangelou Strait.
These cells are activated by common respiratory viruses and other inhaled agents, and prevent airway injury and promote repair.
“Once the problem is resolved, the [immune] system should go back to a normal baseline level. But in some people, the stem cell is changed in a way that continues to promote inflammation and mucus production and ultimately compromises airway function even for normal breathing,” Holtzman said.
Thus, Holtzman’s team is searching for therapeutic targets to control this stem cell response.
The largest of the grants he’s received — at $6.6 million — is the outstanding investigator award from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH), given to researchers with proven expertise in innovative research and considered likely to make major advances. The grant will provide seven years of funding for research intended to further characterize these cells and their underlying mechanisms of action.
The award also supports ongoing efforts to identify pharmacological strategies to manipulate these stem cells. One lead compound has shown promise in animal models, preventing airway inflammation and mucus production after a respiratory viral infection.
Pending clearance from the U.S. Food and Drug Administration, clinical trials for this potential therapy are planned in people with COPD, asthma exacerbations, and related upper airway disorders.
Holtzman also received a NIH Small Business Technology Transfer (STTR) of $300,000 to support a startup company he launched in anticipation of the successful development of these treatments.
“Your first reaction might be to wonder how in the world such similar compounds could be effective in what seem to be such different tissues,” Holtzman said. “But airway and breast tissues and other related sites share secretory function and overlap in how this function is controlled.”
“As a result,” he concluded, “our compounds can be precisely tailored to address whether the dysregulated stem cell is in airway versus breast tissue, or other sites as well.”