Julia K.L. Walker, PhD

Professor in the School of Nursing
Professor - Track V in Medicine
Campus mail 331 Med Sci Res Bldg, DUMC Box 3322, Durham, NC 27710
Phone (919) 668-3252
Email address walke082@mc.duke.edu

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.

Education and Training

  • Ph.D., Queen's University, 1995

Publications

Lin, R, Choi, YH, Zidar, DA, and Walker, JKL. "β-Arrestin-2-Dependent Signaling Promotes CCR4-mediated Chemotaxis of Murine T-Helper Type 2 Cells." American Journal of Respiratory Cell and Molecular Biology 58, no. 6 (June 2018): 745-755.

PMID
29361236
Full Text

Pastva, AM, and Walker, JKL. "Commentary: Central-acting therapeutics alleviate respiratory weakness caused by heart failure-induced ventilatory overdrive." Frontiers in Physiology 9 (January 2018): 554-null.

PMID
29875676
Full Text

Walker, JKL, Theriot, BS, Ghio, M, Trempus, CS, Wong, JE, McQuade, VL, Liang, J, Jiang, D, Noble, PW, Garantziotis, S, Kraft, M, and Ingram, JL. "Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease." American journal of respiratory cell and molecular biology 57, no. 6 (December 2017): 702-710.

PMID
28787175
Full Text

Forkuo, GS, Kim, H, Thanawala, VJ, Al-Sawalha, N, Valdez, D, Joshi, R, Parra, S, Pera, T, Gonnella, PA, Knoll, BJ, Walker, JKL, Penn, RB, and Bond, RA. "Phosphodiesterase 4 Inhibitors Attenuate the Asthma Phenotype Produced by β2-Adrenoceptor Agonists in Phenylethanolamine N-Methyltransferase-Knockout Mice." American Journal of Respiratory Cell and Molecular Biology 55, no. 2 (August 2016): 234-242.

PMID
26909542
Full Text

Pera, T, Hegde, A, Deshpande, DA, Morgan, SJ, Tiegs, BC, Theriot, BS, Choi, YH, Walker, JKL, and Penn, RB. "Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function." Faseb Journal : Official Publication of the Federation of American Societies for Experimental Biology 29, no. 10 (October 2015): 4227-4235.

PMID
26103985
Full Text

Chen, M, Hegde, A, Choi, YH, Theriot, BS, Premont, RT, Chen, W, and Walker, JKL. "Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model." American Journal of Respiratory Cell and Molecular Biology 53, no. 3 (September 2015): 346-354.

PMID
25569510
Full Text

Hegde, A, Strachan, RT, and Walker, JKL. "Quantification of beta adrenergic receptor subtypes in beta-arrestin knockout mouse airways." PloS one 10, no. 2 (January 2015): e0116458-.

PMID
25658948
Full Text

Walker, JKL, and DeFea, KA. "Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma." Current opinion in pharmacology 16 (June 5, 2014): 142-147. (Review)

PMID
24907413
Full Text

Walker, JKL, and Fisher, JT. "Editorial overview: Respiratory: GPCR signaling and the lung." Current opinion in pharmacology 16 (June 2, 2014): iv-vi.

PMID
24888515
Full Text

Penn, RB, Bond, RA, and Walker, JKL. GPCRs and arrestins in airways: implications for asthma. January 2014.

PMID
24292841
Full Text

Pages