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. Thus, we hypothesize that the beta-arrestin-dependent signaling arm, downstream of the β2-AR, is responsible for promoting the asthma phenotype. The translational relevance of this work is high given that the determination of the signaling pathway that is utilized by β2-ARs can be influenced by the molecular signature of the agonist. Thus, our work could lead to the discovery of a β2-AR ligand that bronchodilates the airways without promoting asthma symptoms. In addition to transducing β2-AR-mediated signaling to promote asthma, we hypothesize that beta-arrestin-2 also mediates chemokine receptor signaling and thus, the inflammatory component of asthma. Chemokines, released in response to allergens, dictate the migration of immune cells to the lung in asthma and chemokine receptors are known to signal via both the G-dependent and beta-arrestin-dependent pathways.

Current Appointments & Affiliations

Helene Fuld Health Trust Distinguished Professor of Nursing · 2023 - Present School of Nursing

Professor in the School of Nursing · 2018 - Present School of Nursing

Professor in Medicine · 2020 - Present Medicine, Clinical Science Departments

In the News

Published December 18, 2023

Duke School of Nursing, CTSI Collaborate to Advance Research in Health Equity

Published May 4, 2023

Duke Awards 44 Distinguished Professorships

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Recent Publications

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma.

Journal Article J Allergy Clin Immunol · March 2025 BACKGROUND: Airway tissue eosinophilia can be an observed feature of obesity-associated type 2 (T2) asthma, but the processes mediating this inflammation are unknown. OBJECTIVE: To investigate a process whereby leptin, an adipokine elevated in obesity, pot ... Full text Link to item Cite

Role of Paraoxonase 2 in Airway Epithelial Response to Oxidant Stress.

Journal Article Antioxidants (Basel) · October 31, 2024 Asthma is a widespread chronic lung disease characterized by airway inflammation and hyperresponsiveness. This airway inflammation is classified by either the presence (T2-high) or absence (T2-low) of high levels of eosinophils. Because most therapies for ... Full text Link to item Cite

Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.

Journal Article J Clin Invest · September 15, 2023 Asthma is a chronic inflammatory disease associated with episodic airway narrowing. Inhaled β2-adrenergic receptor (β2AR) agonists (β2-agonists) promote - with limited efficacy - bronchodilation in asthma. All β2-agonists are canonical orthosteric ligands ... Full text Link to item Cite

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Education, Training & Certifications

Queens University · 1995 Ph.D.

Julia K.L. Walker

Overview

Current Appointments & Affiliations

In the News

Recent Publications

Leptin augments IL-13-induced airway eotaxins and submucosal eosinophilia in obesity-associated asthma.

Role of Paraoxonase 2 in Airway Epithelial Response to Oxidant Stress.

Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models.

Recent Grants

Nurse LEADS: Training in Nurse-LEd models of care ADdressing the Social Determinants of Health

Novel Biased Beta2-AR Ligands as Asthma Therapeutics

Mechanisms that Direct Airway Remodeling in Obese Asthma

Education, Training & Certifications