Julia K. Walker, PhD

After receiving a Bachelor of Science degree in Chemistry from Mount Alison University, Dr. Walker pursued a B.Ed. from Ottawa University and was subsequently employed as a board-certified high school chemistry teacher. After teaching for two years she began graduate work focused on cardio-respiratory physiology at Queen’s University in Kingston, Ontario, Canada. Dr. Walker’s postdoctoral training in cell biology at Duke University focused on receptor signaling pathways; in particular those of G protein-coupled receptors (GPCRs). GPCRs are the largest family of cell surface receptors and more than half of all medically prescribed drugs target their function.
Dr. Walker’s research, which focuses on understanding the cellular pathophysiological mechanisms that underlie lung disease (in particular asthma) has been independently funded since 2004, and she currently holds the Duke University rank of Professor in Nursing and Pulmonary Medicine. Dr. Walker is an expert in GPCR regulation by beta-arrestin proteins and the application of this to the pathophysiology of asthma. Currently, Dr. Walker’s research focus includes the study of novel β-2-adrenoceptor ligands and biased signaling in the treatment of asthma. This research holds great potential to rapidly improve quality of life for asthmatics.
Dr. Walker has published 41 peer-reviewed basic research, 5 review or opinion articles and 2 book Chapters, and has been an invited speaker at numerous seminar forums both Nationally and Internationally. She has been recognized by her peers with ATS-sponsored awards such as the Ann Woolcock memorial and ATS Young Investigator awards.
Dr. Walker teaches Physiology to Nursing Students using a deep learning approach which asks students to comprehend concepts rather than memorize facts. This approach facilitates retention of information and development of critical thinking skills. Dr. Walker has received the Outstanding MSN Faculty and DUNAP Faculty of the Year awards.

Academic Program Affiliations
Education
  • Ph.D. - Queens University
  • M.Sc. - Queen's University
  • B.Ed. - University of Ottawa
  • B.Sc. - Mount Allison University
Awards and Honors
  • 2014 || Faculty of the Year, Duke University Nurse Anesthesia Program
  • 2014 || Outstanding MSN Faculty Award, Duke University School of Nursing
  • 2009 || ATS-Appointed Young Investigator to the 49th Annual Japanese Respiratory Society Meeting, American Thoracic Society
  • 2004 || Ann Woolcock Memorial Award, ATS - American Thoracic Society
  • 1999 || Fellowship, Medical Council of Canada
  • 1997 || Fellowship, Canadian Lung Association/Medical Research Council
  • 1996 || Abrahams’ Prize in Physiology, Queen’s University
  • 1995 || Ontario Graduate Student Award
  • 1995 || Queen's Graduate Award, Queen’s University
  • 1994 || Dean's Award, Queen's University
  • 1994 || Queen's Graduate Fellowship, Queen’s University
  • 1993 || Fellowship, Ontario Thoracic Society
  • 1992 || Ontario Graduate Student Award
  • 1991 || Dean's Award, Queen’s University
  • 1991 || Fellowship, Ontario Thoracic Society
  • 1987 || Murray Sears Memorial Prize in Chemistry, Mount Allison University
  • 1985 || Dean's Scholarship, Academic, Mount Allison University
  • 1985 || Dean's Scholarship, Athletic Achievement, Mount Allison University
  • 1984 || Ralph Pickard Bell Entrance Scholarship, Mount Allison University
  • 1983 || Carleton Board of Education Bursary for Gifted Students
Areas of Interest
Physiology, G protein-coupled receptor signaling, Beta-arrestin role in asthma pathogenesis, optimizing beta-2-adrenergic receptor biased signaling in asthma
Representative Publications
  • 2004 -- PubMed # : 14565944 -- Walker, J. K. and Gainetdinov, R. R. and Feldman, D. S. and McFawn, P. K. and Caron, M. G. and Lefkowitz, R. J. and Premont, R. T. and Fisher, J. T. G protein-coupled receptor kinase 5 regulates airway responses induced by muscarinic receptor activation. Am J Physiol Lung Cell Mol Physiol. February, 2004 286(2); L312-9.
  • 2003 -- PubMed # : 12925697 -- Walker, J. K. and Fong, A. M. and Lawson, B. L. and Savov, J. D. and Patel, D. D. and Schwartz, D. A. and Lefkowitz, R. J. Beta-arrestin-2 regulates the development of allergic asthma. J Clin Invest. August, 2003 112(4); 566-74. PMC171386
  • 2003 -- PubMed # : 12626335 -- Whitehead, G. S. and Walker, J. K. and Berman, K. G. and Foster, W. M. and Schwartz, D. A. Allergen-induced airway disease is mouse strain dependent. Am J Physiol Lung Cell Mol Physiol. July, 2003 285(1); L32-42.
  • 2002 -- PubMed # : 11978791 -- Shetzline, M. A. and Walker, J. K. and Valenzano, K. J. and Premont, R. T. Vasoactive intestinal polypeptide type-1 receptor regulation. Desensitization, phosphorylation, and sequestration. J Biol Chem. July, 2002 277(28); 25519-26.
  • 1999 -- PubMed # : 10531354 -- Walker, J. K. and Premont, R. T. and Barak, L. S. and Caron, M. G. and Shetzline, M. A. Properties of secretin receptor internalization differ from those of the beta(2)-adrenergic receptor. J Biol Chem. October, 1999 274(44); 31515-23.
  • 2005 -- PubMed # : 15917400 -- Raehal, K. M. and Walker, J. K. and Bohn, L. M. Morphine side effects in beta-arrestin 2 knockout mice. J Pharmacol Exp Ther. September, 2005 314(3); 1195-201.
  • 2006 -- PubMed # : 16474097 -- Walker, J. K. and Ahumada, A. and Frank, B. and Gaspard, R. and Berman, K. and Quackenbush, J. and Schwartz, D. A. Multistrain genetic comparisons reveal CCR5 as a receptor involved in airway hyperresponsiveness. Am J Respir Cell Mol Biol. June, 2006 34(6); 711-8.
  • 1999 -- PubMed # : 10624964 -- Gainetdinov, R. R. and Bohn, L. M. and Walker, J. K. and Laporte, S. A. and Macrae, A. D. and Caron, M. G. and Lefkowitz, R. J. and Premont, R. T. Muscarinic supersensitivity and impaired receptor desensitization in G protein-coupled receptor kinase 5-deficient mice. Neuron. December, 1999 24(4); 1029-36.
  • 2008 -- PubMed # : 18337459 -- Deshpande, D. A. and Theriot, B. S. and Penn, R. B. and Walker, J. K. Beta-arrestins specifically constrain beta2-adrenergic receptor signaling and function in airway smooth muscle. FASEB J. July, 2008 22(7); 2134-41. PMC3514410
  • 1998 -- PubMed # : 9506976 -- Shetzline, M. A. and Premont, R. T. and Walker, J. K. and Vigna, S. R. and Caron, M. G. A role for receptor kinases in the regulation of class II G protein-coupled receptors. Phosphorylation and desensitization of the secretin receptor. J Biol Chem. March, 1998 273(12); 6756-62.
  • 2004 -- PubMed # : 15020293 -- Hollingsworth 2nd, J. W. and Cook, D. N. and Brass, D. M. and Walker, J. K. and Morgan, D. L. and Foster, W. M. and Schwartz, D. A. The role of Toll-like receptor 4 in environmental airway injury in mice. Am J Respir Crit Care Med. July, 2004 170(2); 126-32.
  • 1999 -- PubMed # : 10198406 -- Walker, J. K. and Peppel, K. and Lefkowitz, R. J. and Caron, M. G. and Fisher, J. T. Altered airway and cardiac responses in mice lacking G protein-coupled receptor kinase 3. Am J Physiol. April, 1999 276(4 Pt 2); R1214-21.
  • 1997 -- PubMed # : 9128905 -- Walker, J. K. and Lawson, B. L. and Jennings, D. B. Breath timing, volume and drive to breathe in conscious rats: comparative aspects. Respir Physiol. March, 1997 107(3); 241-50.
  • 1999 -- PubMed # : 10030450 -- Walker, J. K. and Jennings, D. B. Respiratory effects of pressor and depressor agents in conscious rats. Can J Physiol Pharmacol. June, 1999 76(7-8); 707-14.
  • 1996 -- PubMed # : 9028585 -- Walker, J. K. and Jennings, D. B. Ventilatory effects of angiotensin and vasopressin in conscious rats. Can J Physiol Pharmacol. November, 1996 74(11); 1258-64.
  • 2012 -- PubMed # : 22013997 -- Lin, R. and Degan, S. and Theriot, B. S. and Fischer, B. M. and Strachan, R. T. and Liang, J. and Pierce, R. A. and Sunday, M. E. and Noble, P. W. and Kraft, M. and Brody, A. R. and Walker, J. K. Chronic treatment in vivo with β-adrenoceptor agonists induces dysfunction of airway β(2) -adrenoceptors and exacerbates lung inflammation in mice. Br J Pharmacol. April, 2012 165(7); 2365-77. PMC3413869
  • 2000 -- PubMed # : 10655494 -- Claing, A. and Perry, S. J. and Achiriloaie, M. and Walker, J. K. and Albanesi, J. P. and Lefkowitz, R. J. and Premont, R. T. Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proc Natl Acad Sci U S A. February, 2000 97(3); 1119-24. PMC15541
  • 1994 -- PubMed # : 7928878 -- Walker, J. K. and Jennings, D. B. Angiotensin mediates stimulation of ventilation after vasopressin V1 receptor blockade. J Appl Physiol (1985). June, 1994 76(6); 2517-26.
  • 2007 -- PubMed # : 17255472 -- Vincent, S. G. and Waddell, A. E. and Caron, M. G. and Walker, J. K. and Fisher, J. T. A murine model of hyperdopaminergic state displays altered respiratory control. FASEB J. May, 2007 21(7); 1463-71.
  • 1993 -- PubMed # : 8482661 -- Ohtake, P. J. and Walker, J. K. and Jennings, D. B. Renin-angiotensin system stimulates respiration during acute hypotension but not during hypercapnia. J Appl Physiol (1985). March, 1993 74(3); 1220-8.
  • 1996 -- PubMed # : 8964741 -- Overgaard, C. B. and Walker, J. K. and Jennings, D. B. Respiration during acute hypoxia: angiotensin- and vasopressin-receptor blocks. J Appl Physiol (1985). March, 1996 80(3); 810-7.
  • 2011 -- PubMed # : 21175591 -- Walker, J. K. and Penn, R. B. and Hanania, N. A. and Dickey, B. F. and Bond, R. A. New perspectives regarding β(2) -adrenoceptor ligands in the treatment of asthma. Br J Pharmacol. May, 2011 163(1); 18-28. PMC3085865
  • 2006 -- PubMed # : 16809636 -- Garantziotis, S. and Brass, D. M. and Savov, J. and Hollingsworth, J. W. and McElvania-TeKippe, E. and Berman, K. and Walker, J. K. and Schwartz, D. A. Leukocyte-derived IL-10 reduces subepithelial fibrosis associated with chronically inhaled endotoxin. Am J Respir Cell Mol Biol. December, 2006 35(6); 662-7. PMC2643294
  • 2005 -- PubMed # : 15833764 -- Savov, J. D. and Brass, D. M. and Lawson, B. L. and McElvania-Tekippe, E. and Walker, J. K. and Schwartz, D. A. Toll-like receptor 4 antagonist (E5564) prevents the chronic airway response to inhaled lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol. August, 2005 289(2); L329-37.
  • 2012 -- PubMed # : 23012429 -- Nichols, H. L. and Saffeddine, M. and Theriot, B. S. and Hegde, A. and Polley, D. and El-Mays, T. and Vliagoftis, H. and Hollenberg, M. D. and Wilson, E. H. and Walker, J. K. and DeFea, K. A. β-Arrestin-2 mediates the proinflammatory effects of proteinase-activated receptor-2 in the airway. Proc Natl Acad Sci U S A. October, 2012 109(41); 16660-5. PMC3478622
  • 2013 -- PubMed # : 23991664 -- Forkuo, G. S. and Thanawala, V. J. and Al-Sawalha, N. and Bond, R. A. and Walker, J. K. Reply: Adverse effects of long-acting beta-agonists on airway hyperresponsiveness. Am J Respir Cell Mol Biol. September, 2013 49(3); 502.
  • 2013 -- PubMed # : 23204390 -- Thanawala, V. J. and Forkuo, G. S. and Al-Sawalha, N. and Azzegagh, Z. and Nguyen, L. P. and Eriksen, J. L. and Tuvim, M. J. and Lowder, T. W. and Dickey, B. F. and Knoll, B. J. and Walker, J. K. and Bond, R. A. β2-Adrenoceptor agonists are required for development of the asthma phenotype in a murine model. Am J Respir Cell Mol Biol. February, 2013 48(2); 220-9.
  • 1995 -- PubMed # : 8567518 -- Walker, J. K. and Jennings, D. B. During acute hypercapnia vasopressin inhibits an angiotensin drive to ventilation in conscious dogs. J Appl Physiol (1985). September, 1995 79(3); 786-94.
  • 2010 -- PubMed # : 20399707 -- Dickey, B. F. and Walker, J. K. and Hanania, N. A. and Bond, R. A. beta-Adrenoceptor inverse agonists in asthma. Curr Opin Pharmacol. June, 2010 10(3); 254-9. PMC2905467
  • 2013 -- PubMed # : 23408785 -- Walker, J. K. and Kraft, M. and Fisher, J. T. Assessment of murine lung mechanics outcome measures: alignment with those made in asthmatics. Front Physiol. February, 2013 3(491); . PMC3569663
  • 2011 -- PubMed # : 20348208 -- Pastva, A. M. and Walker, J. K. and Maddox, L. A. and Mukherjee, S. and Giamberardino, C. and Hsia, B. and Potts, E. and Zhu, H. and Degan, S. and Sunday, M. E. and Lawson, B. L. and Korfhagen, T. R. and Schwartz, D. A. and Eu, J. P. and Foster, W. M. and McMahon, T. J. and Que, L. and Wright, J. R. Nitric oxide mediates relative airway hyporesponsiveness to lipopolysaccharide in surfactant protein A-deficient mice. Am J Respir Cell Mol Biol. February, 2011 44(2); 175-84. PMC3049231
  • 2010 -- PubMed # : 19805483 -- Hollingsworth, J. W. and Theriot, B. S. and Li, Z. and Lawson, B. L. and Sunday, M. and Schwartz, D. A. and Walker, J. K. Both hematopoietic-derived and non-hematopoietic-derived {beta}-arrestin-2 regulates murine allergic airway disease. Am J Respir Cell Mol Biol. September, 2010 43(3); 269-75. PMC2933545
  • 2008 -- PubMed # : 18587448 -- Ryu, H. and Walker, J. K. and Kim, S. and Koo, N. and Barak, L. S. and Noguchi, T. and Kang, B. Y. and Kim, K. Regulation of M2-type pyruvate kinase mediated by the high-affinity IgE receptors is required for mast cell degranulation. Br J Pharmacol. July, 2008 154(5); 1035-46. PMC2451040
  • 2007 -- PubMed # : 17969115 -- Driehuys, B. and Walker, J. and Pollaro, J. and Cofer, G. P. and Mistry, N. and Schwartz, D. and Johnson, G. A. 3He MRI in mouse models of asthma. Magn Reson Med. November, 2007 58(5); 893-900. PMC2746053
  • 2000 -- PubMed # : 10915639 -- Walker, J. K. and Gainetdinov, R. R. and Mangel, A. W. and Caron, M. G. and Shetzline, M. A. Mice lacking the dopamine transporter display altered regulation of distal colonic motility. Am J Physiol Gastrointest Liver Physiol. August, 2000 279(2); G311-8.
  • 1995 -- Jennings, D. B. and Walker, J. K. L., and Ohtake, P. J. Central effects and interactions of the renin-angiotensin system and vasopressin on ventilation and PaCO2 1995 203-224.
  • 1998 -- PubMed # : 9795743 -- Walker, J. K. and Jennings, D. B. Ventilatory and metabolic effects of hypercapnia in conscious rats: AVP V1 receptor block. Can J Physiol Pharmacol. April, 1998 76(4); 361-6.
  • 2014 -- PubMed # : 24292841 -- Penn, R. B. and Bond, R. A. and Walker, J. K. GPCRs and Arrestins in Airways: Implications for Asthma. Handb Exp Pharmacol. 2014 219 387-403.
  • 2014 -- PubMed # : 24907413 -- Walker, J. K. and DeFea, K. A. Role for β-arrestin in mediating paradoxical β2AR and PAR2 signaling in asthma. Curr Opin Pharmacol. 16C 142-147.
  • 2014 -- PubMed # : 24888515 -- Walker, J. K. and Fisher, J. T. Editorial overview: Respiratory: GPCR signaling and the lung. Curr Opin Pharmacol. 16 iv-vi.
  • 2015 -- PubMed # : 25658948 -- Hegde, A. and Strachan, R. T. and Walker, J. K. Quantification of Beta adrenergic receptor subtypes in Beta-arrestin knockout mouse airways. PLoS One. February 6, 2015 10(2); e0116458.
  • 2015 -- PubMed # : 25569510 -- Chen, M. and Hegde, A. and Choi, Y. H. and Theriot, B. S. and Premont, R. T. and Chen, W. and Walker, J. K. Genetic Deletion of β-Arrestin-2 and the Mitigation of Established Airway Hyperresponsiveness in a Murine Asthma Model. Am J Respir Cell Mol Biol. 53(3); 346-54. PMC4566063
  • 2015 -- PubMed # : 26103985 -- Pera, T. and Hegde, A. and Deshpande, D. A. and Morgan, S. J. and Tiegs, B. C. and Theriot, B. S. and Choi, Y. H. and Walker, J. K. and Penn, R. B. Specificity of arrestin subtypes in regulating airway smooth muscle G protein-coupled receptor signaling and function. FASEB J. October, 2015 29(10); 4227-35. PMC4566941
  • 2016 -- Forkuo, GS., Kim, H., Thanawala, VJ., Al-Sawalha, N., Valdez, D., Joshi, R., Knoll, BJ., Walker, J.K.L., Penn, RB. and RA. Bond Administration of PDE4 inhibitors in mice lacking epinephrine attenuates restoration of the asthma phenotype produced by beta-2-adrenoceptor agonists Am J Respir Cell Mol Biol. August, 2016 55(2); 234-42.
  • 2017 -- PubMed # : 28787175 -- Walker, J. K. and Theriot, B. S. and Ghio, M. and Trempus, C. S. and Wong, J. E. and McQuade, V. L. and Liang, J. and Jiang, D. and Noble, P. W. and Garantziotis, S. and Kraft, M. and Ingram, J. L. Targeted HAS2 Expression Lessens Airway Responsiveness in Chronic Murine Allergic Airway Disease. Am J Respir Cell Mol Biol. 57(6); 702-710.
Grant Funding (Selected)
  • Optimizing Beta-Adrenoceptor Signaling Bias in Asthma
    National Institutes of Health
    1R01-AI110007-01A1
    06/2014 to 05/2019
    Role: Principal Investigator
    Project Goals: We propose studies to solve the “beta-2 adrenoceptor paradox” in asthma by establishing the cell-specific role of beta-2 adrenoceptor signaling pathways in regulating the asthma phenotype, and identifying from among current and newly generated beta-2 adrenoceptor ligands or modulators those with biased signaling properties that are optimal in their ability to antagonize pathogenic beta-2 adrenoceptor signaling via arrestins, yet promote beneficial G protein signaling.
  • Host Factors in Regulation of Inflammatory and Fibroproliferative Lung Disease
    Cedars Sinai Medical Center
    001073456
    06/2014 to 05/2015
    Role: PI
  • Mechanisms of Beta-blocker Induced Improvements in Asthma
    NIH-NHLBI
    AI079236-03
    06/2013 to 05/2018
    Role: Co-Principal Investigator
    Project Goals: The primary goal of this project is to determine the mechanism of the proasthmatic effect of β2AR signaling.
  • Host factors in regulation of inflammatory and fibroproliferative lung disease
    NIH-NHLBI
    08/2012 to 07/2017
    Role: Animal Core Principal Investigator
    Project Goals: The primary goal of this project is to determine the mechanism by which host factors interact with lung injury or allergen exposure to promote lung inflammation and fibrosis.
  • Modeling beta2-adrenergic receptor desensitization in mouse airway smooth muscle
    Aerie Pharmaceuticals
    03/2012 to 02/2013
    Role: Principal Investigator
    Project Goals: The overall goal of this research is to evaluate the immediate and prophylactic effects of Aerie Pharmaceutical compounds (rho-kinase super inhibitors) on asthmatic inflammation and associated airway hyperresponsiveness in mice.
  • Arrestin selectivity for GPCRs in airway smooth muscle
    NIH-NHLBI
    R01-HL093103-01A2
    04/2010 to 03/2014
    Role: Co-Principal Investigator
    Project Goals: The primary goal of this project is to delineate the functional selectivity of β arrestin-mediated desensitization of pro-and anti-contractile GPCRs in airway smooth muscle.
  • T cell metabolism as a determinant of differentiation in allergic asthma
    NIH-NHLBI
    R01-HL108006-01
    04/2010 to 03/2015
    Role: Collaborator Investigator
    Project Goals: The primary goal of this project is to delineate the mechanism by which glucose transporter function influences T cell metabolism and function in allergic asthma.
  • T cell function in asthma depends on a novel signaling pathway
    NIH-NHLBI
    R01-HL084123
    02/2008 to 01/2013
    Role: Principal Investigator
    Project Goals: The primary goal of this project is to delineate the mechanism by which beta arrestin-2 regulates T cell chemotaxis in asthma.
  • Modeling beta2-adrenergic receptor desensitization in mouse airway smooth muscle
    Sepracor, Inc.
    10/2005 to 12/2007
    Role: Principal Investigator
    Project Goals: The overall goal of this research is to develop a mouse model of beta2-adrenergic receptor desensitization in airway smooth muscle and to test the effects of levalbuterol in this model. 2-adrenergic receptor dysfunction occurs in human asthmatics precipitating morbidity and mortality.
  • Mouse Models of Heart, Lung and Blood Diseases
    NIH-NHLBI
    U01 HL66611 renewal
    09/2004 to 08/2008
    Role: Principal Investigator (subcontract: David A. Schwartz)
    Project Goals: The overall goal of this research is to provide new resources for identifying the genes underlying lung disorders by examining the physiologic and biologic response of the lung to complementary challenges in ENU mutagenized mice.
  • The role for beta-arrestin-2 in regulating lung inflammatory disorders
    Veterans Administration Merit Review Entry Program
    07/2004 to 06/2007
    Role: Principal Investigator
    Project Goals: The overall goal of this project is to understand the mechanisms by which beta-arrestin-2 regulates the development of allergen induced airway disease
  • Modeling beta-2-adrenergic receptor desensitization in mouse airway smooth muscle
    Norak Biosciences
    07/2004 to 01/2005
    Role: Principal Investigator
    Project Goals: The overall goal of this research is to develop a mouse model of beta2-adrenergic receptor desensitization in airway smooth muscle. This phenomenon occurs in human asthmatics precipitating increased morbidity and mortality.
  • The Pathogenesis and Genetics of Environmental Asthma
    NIH/NIEHS
    5 U19 ES012496-05
    09/2003 to 06/2009
    Role: Administrative Core Consultant
    The overall theme of this PPG is to understand further the pathogenesis and genetics of asthma by studying environmental airway disease.
  • Mouse Models of Heart, Lung and Blood Diseases
    NIH-NHLBI
    U01 HL66611
    09/2000 to 09/2004
    Role: Consultant
    Project Goals: The overall goal of this research is to provide new resources for identifying the genes underlying lung disorders by examining the physiologic and biologic response of the lung to complementary challenges in ENU mutagenized mice
  • Role of GPCR regulatory mechanisms in the pathophysiology of asthma
    Sandler Program for Asthma Research
    07/2000 to 06/2004
    Role: Co-Principal Investigator
    Project Goals: The major goals of this project are to screen mice with a genetic deletion of a G protein-coupled receptor kinase or an arrestin protein for altered airway responsiveness or airway inflammation in the context of allergic or non-allergic asthma.
  • Mechanisms that Direct Airway Remodeling in Obese Asthma
    NIH-NHLBI
    HL213214
    09/2017 to 06/2021
    Role: Co-Investigator
    Obesity contributes to asthma pathobiology. The primary goal of this project is to define mechanisms whereby leptin and glucagon-like peptide-1 modulate fibrotic processes and IL-13 signaling in airway fibroblasts in early-onset, obese asthma.
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