Nora Barrett, M.D. is studying a family of inflammatory molecules produced in abundance in the lungs when a person has an asthma attack. These molecules, called cysteinyl leukotrienes (cysLTs), are extremely potent in causing the airway constriction and breathlessness that occurs in asthma attacks.
"We know that patients with asthma generate high levels of cysLTs during asthma attacks triggered by viruses, cold air, exercise, aspirin, or allergy to cats, mold, or other allergens," says Dr. Barrett, an allergist/immunologist at Brigham and Women's Hospital in Boston and Assistant Professor of Medicine at Harvard Medical School.
Three leukotriene receptors have been identified, but current treatment only blocks one of them. Recently, Dr. Barrett's lab discovered that the third leukotriene receptor, also called GPR99, has important functions in the nose and lung. With a grant from the American Lung Association and the American Academy of Allergy, Asthma and Immunology, Dr. Barrett is studying the role of GPR99 in asthma
She has found that GPR99 is on cells called epithelial cells that line the airways of the nose, trachea and lungs (the finding was recently published in the journal PNAS). Since learning that those with this receptor can develop inflammation and mucus in the airways after inhaling a common airborne allergen, while those without the receptor do not; Dr. Barrett hopes that a better understanding of how GPR99 on airway epithelial cells regulates the development of inflammation in the lung will lead to treatment that would block the receptor. "This could prevent excessive mucus generation in the lungs that obstructs breathing," she says. "It could be an important addition to the current treatment options in asthma."
The implications for this research could reach beyond asthma to other airway diseases, she adds. "Our early molecular studies demonstrate that this receptor regulates mucus production in the absence of asthma. Targeting this receptor may teach us how to improve the function of lung-lining cells in other airway diseases such as COPD or cystic fibrosis."
Dr. Barrett says the American Lung Association /AAAAI grant is essential for her lab to gather enough data to apply for a larger grant, such as those available from the National Institutes of Health. "Federal funding agencies, foundations, and industry sponsors often prioritize funding low-risk applications with a significant amount of preliminary data," she notes. "But it takes a very long time to get that data. Funding early studies, such as this one, is critical to get to that point. More importantly, funding this basic biology can help to identify the next generation of therapeutic targets in asthma and other airway disorders."
Page last updated: March 2, 2020