Julia K.L. Walker

Broadly, my research focuses on the role for G protein-coupled receptors in the pathophysiology of asthma. Asthma is a complex disease characterized by airway inflammation, hyperresponsiveness and remodeling. G protein-coupled receptors figure largely in the pathology and treatment of this disease. For example, beta-agonists, the rescue medication inhaled by asthmatics, act at airway smooth muscle beta2-adrenergic receptors (β2-AR) to relax the airways. However, excessive use of beta-agonists has been associated with clinical worsening of asthma control and increased mortality. β2-ARs can signal through two well characterized and independent signaling pathways; a G protein-dependent pathway and a beta-arrestin-dependent pathway. Previously we showed that mice lacking beta-arrestin-2 do not develop the symptoms of allergic airway inflammatory disease and that T cell and eosinophil migration to the lung is impaired in these mice. Similarly, others have shown that the asthma phenotype is significantly reduced in mice lacking global expression of β2-ARs. Taken together, this work provides a mechanistic explanation that may explain why excessive use of beta-agonists by some asthma patients worsens the disease. Our research has played a major role in starting and continuing efforts to find compounds that can bias β2-AR signaling, with the goal of improving asthma therapy. Several of these lead compounds are being tested in my laboratory using in vivo asthma models.

Through my role as Director of the Biomarker Laboratory at Duke University School of Nursing, I am also engaged in stress biology research that examines social drivers of health and disease.