Discovering Asthma’s Biological Roots

Asthma has traditionally been defined by symptoms of the disease: breathlessness caused by airway inflammation and constriction of the muscles surrounding the airways. That relatively simple description obscures a complex variety of causes, disease pathways and responses to medication that lead many in the medical community to consider asthma as several different diseases masquerading as one. Max Seibold, PhD, associate professor in the Center for Genes, Environment and Heath, has developed several new investigational techniques that allow researchers to delve deeply into the biological roots of this deceptively complex disease.

Advanced genetic sequencing allows Max Seibold, PhD, and National Jewish Health to delve into the biological roots of asthma.Advanced genetic sequencing allows Max Seibold, PhD, and National Jewish Health to delve into the biological roots of asthma.

Dr. Seibold’s research has focused largely on epithelial cells lining the airways, which drive much of the pathological processes in asthma. Difficult cells to investigate, they have previously required invasive bronchoscopies to obtain samples from patients. In 2014, Dr. Seibold showed that epithelial cells, obtained much more easily from a patient’s nose, are an excellent proxy for airway epithelial cells, expressing almost exactly the same genes. In 2015, he used the revolutionary CRISPR-Cas9 gene-editing technique to develop a powerful way to study the function of individual genes in epithelial cells. Most recently, he and his colleagues adapted existing techniques to transform epithelial cells into their stem cell parent, allowing researchers to examine the evolution of healthy cells into pathological ones.

These and other advanced genetic techniques have allowed Dr. Seibold and his colleagues to discover the first gene variant associated with a specific subtype of asthma, known as type 2. He recently discovered how alternative splicing of the IL-33 gene drives type 2 asthma, and identified genetic variants associated with asthma that follows infection with respiratory syncytial virus, or RSV, a common virus among young children.