Specialty Areas: asthma, sarcoidosis
Chronology: BA chemistry: University of North Carolina at Chapel Hill, 1988; MD: University of North Carolina School of Medicine,1992; Resident: Vanderbilt University, 1992-1995; Pulmonary and Critical Care Fellow: University of North Carolina Hospitals, 1995-1998; Teaching Fellow: Department of Medicine, UNC School of Medicine, 1998-2000; Instructor: Department of Medicine, UNC School of Medicine, 2000-2002; Assistant Professor, Department of Medicine, UNC School of Medicine, 2002-2009; Associate Professor, Department of Medicine, UNC School of Medicine, 2009-present
Our laboratory has focused on defining the role of mast cells and extracellular nucleotide (ATP) and nucleoside (adenosine) signaling in the pathogenesis of lung diseases. We have discovered roles for adenosine signaling through specific adenosine receptors in mast cell function, bronchoconstriction of the airways, and mucociliary clearance. The lab is presently investigating the contribution of ATP signaling to ozone-induced asthma exacerbation and is developing a project to test the hypothesis that ATP contributes to the pathogenesis of ventilator-induced lung injury in viral pneumonia secondary to SARS-CoV-2. Finally we collaborate with other investigators in academia and industry to identify new targets and test the safety and efficacy of novel therapies in lung disease models.
Arthur GK, Ehrhardt-Humbert LC, Snider DB, Jania C, Tilley SL, Metcalfe DD, Cruse G. The FcεRIβ homologue, MS4A4A, promotes FcεRI signal transduction and store-operated Ca2+ entry in human mast cells. Cellular Signaling. 2020 Jul;71:109617. doi: 10.1016/j.cellsig.2020.109617. Epub 2020 Mar 30
Hua X; Vijay R; Athmer J; Meyerholz D, Pagedar N, Tilley SL, Perlman S. Nasal priming by murine coronavirus enhances lung innate and adaptive immunity against lethal viral pneumonia. Journal of Clinical Investigation Insight. 2018 Jun 7;3(11). PMID: 29875310
Wu T, Huang J, Moore PJ, Little MS, Walton WG, Fellner RC, Alexis NE, Di Y, Peter, Redinbo MR, Tilley SL, Tarran R. Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor. Nature Communications. 2017 Feb 6;8:14118 PMID: 28165446
Hua X, Naselsky WC, Jania CM, Chason KD, Huang JJ. Doerschuk CM, Graham SM, Senior BA, Tilley SL. Mast cell deficiency limits the development of chronic rhinosinusitis in mice. Annals of Otology, Rhinology, and Laryngology. 2016. Apr; 125(4):290-6. PMID: 26681624
Sorrentino JA, Krishnamurthy J, Tilley SL, Alb JG Jr, Burd CE, Sharpless NE. p16INK4a reporter mice reveal age-promoting effects of environmental toxicants. Journal of Clinical Investigation. 2014 Jan; 124(1):169-73. PMID: 24334456
Hua X, Chason K, Jania C, Acosta T, Ledent C, Tilley SL. Gs-coupled adenosine receptors differentially limit antigen-induced mast cell activation. Journal of Pharmacology and Experimental Therapeutics. 2013 Feb; 344(2):426-35. PMID: 23149337
Hua X, Naselsky WC, Bennett WD, Ledent C, Senior BA, Tilley SL. Adenosine increases nasal mucociliary clearance rate in mice through A2A and A2B adenosine receptors. Laryngoscope. 2013 Feb; 123(2):306-10. PMID: 22965898
Allen IC, Jania CM, Wilson JE, Tekeppe EM, Hua X, Brickey WJ, Kwan M, Koller BH, Tilley SL, Ting JP. Analysis of NLRP3 in the development of allergic airway disease in mice. J Immunol. 2012 Mar 15;188(6):2884-93. PMID: 22279123
Hua X, Chason KD, Patel JY, Naselsky WC, Tilley SL. IL-4 amplifies the pro-inflammatory effect of adenosine in human mast cells by changing expression levels of adenosine receptors. PLoS One. 2011;6(9): e24947. PMID: 21966389
Kovarova M, Latour AM, Chason KD, Tilley SL, Koller BH. Human embryonic stem cells: a source of mast cells for the study of allergic and inflammatory diseases. Blood. 2010 May 6;115(18):3695-703. PMID: 20200352
Hua X, Chason KD, Fredholm BB, Deshpande DA, Penn RB, Tilley SL. Adenosine induces airway hyperresponsiveness through activation of A3 receptors on mast cells. Journal of Allergy and Clinical Immunology. 2008 Jul; 122(1):107-13, 113.e1-7. PMID: 18472152
Mall MA, Harkema JR, Trojanek JB, Treis D, Livraghi A, Schubert S, Zhou Z, Kreda SM, Tilley SL, Hudson EJ, O’Neal WK, Boucher RC. Development of chronic bronchitis and emphysema in βENaC overexpressing mice. American Journal of Respiratory and Critical Care Medicine. 2008 Apr 1;177(7):730-42. PMID: 18079494.
Hua X, Erikson CJ, Chason KD, Rosebrock CN, Deshpande DA, Penn RB, Tilley SL. Involvement of A1 adenosine receptors and neural pathways in adenosine induced bronchoconstriction in mice. American Journal of Physiology Lung Cellular and Molecular Physiology. 2007 Jul; 293(1):L25-32. PMID: 17468137
Hua, X, Kovarova M, Chason KD, Nguyen M, Koller BH, Tilley SL. Enhanced mast cellactivation in mice deficient in the A2B adenosine receptor. J Exp Med. 2007Jan 22; 204(1):117-28. Journal of Experimental Medicine. 2007 Apr 16:204(4):963. PMID: 17200408
Tilley SL, Jaradat M, Stapleton C, Dixon D, Hua X, Erikson CJ, McCaskill JG, Chason, KD, Liao G, Jania L, Koller BH, Jetten AM. Retinoid-related orphan receptor γ controls immunoglobulin production and Th1/Th2 cytokine balance in the adaptive immune response to allergen. Journal of Immunology. 2007 Mar 1; 178(5):3208-18. PMID: 17312169
Tilley SL, Boucher, RC. A1 antagonism in asthma: better than coffee? Journal of Clinical Investigation. 2005 Jan; 115(1):13-16. PMID: 15630434
Tilley SL, Tsai M, Williams CM, Wang ZS, Erikson CJ, Galli SJ, Koller BH. Identification of A3 receptor- and mast cell-dependent and -independent components of adenosine-mediated airway responsiveness in mice. Journal of Immunology. 2003 Jul 1; 171(1):331-7. PMID: 12817015
Tilley SL, Hartney JM, Erikson CJ, Jania C, Nguyen M, Stock J, McNeisch J, Valancius C, Panettieri RA Jr, Penn RB, Koller BH. Receptors and pathways mediating the effects of prostaglandin E2 on airway tone. American Journal of Physiology. 2003 Apr; 284:L599-L606. PMID: 12618422
Tilley SL, Coffman TM, Koller BH. Mixed messages: modulation of inflammation and immune response by prostaglandins and thromboxanes. Journal of Clinical Investigation. 2001 Oct; 108:15-23. PMID: 11435451
Tilley SL, Wagoner VA, Salvatore CA, Jacobson MA, Koller BH. Adenosine and inosine increase cutaneous vasopermeability by activating A3 receptors on mast cells. Journal of Clinical Investigation. 2000 Feb; 105(3):361-7. doi: 10.1172/JCI8253. PMID: 10675362
Tilley SL, Salvatore CA, Latour AM, Fletcher DS, Koller BH, Jacobson MA. Disruption of the A3 adenosine receptor gene in mice and its effect on stimulated inflammatory cells. Journal of Biological Chemistry. 2000 Feb 11; 275(6):4429-34. PMID: 10660615.