Robert Tarran, PhD

Associate Professor

Specialty Areas: Airway Epithelial Cell Biology and Airway Surface Liquid Homeostasis in CF and COPD

Research Focus: It has recently been shown that a critical component of airways innate defense is the thin (7 µm) liquid layer lining airway surfaces, the periciliary liquid (PCL), that provides a low viscosity solution for ciliary beating and acts a lubricant layer for mucus transport. Normal airways appear to be able to sense the PCL volume and adjust ion channel activity accordingly by unknown mechanisms. A proposed model for ASL volume regulation is shown in Figure 1.

Apical membrane ion channel activity controls the amount of salt (and water) on airway surfaces and hence, PCL volume and mucus hydration levels. It has recently been proposed that the initiating event in CF lung disease is depletion of the PCL due to abnormal ion channel activity (i.e. a lack of CFTR), which causes dehydrated mucus to adhere to airway surfaces, preventing it from being cleared (Fig. 2), causing increased bacterial infections.

The long term goal of this laboratory is to understand how homeostasis of PCL volume occurs in airway epithelia under normal and pathophysiological conditions. Currently, research in the Tarran lab is focused on three main areas, listed below, and we utilize cell biological and biochemical techniques coupled with in vivo translational approaches to address these questions:

  1. Regulation of epithelial cell function by the extracellular environment: We have hypothesized that nucleotides, proteases and other molecules contained in the ASL (ATP for example) can regulate airway ion transport. Fig. 3 depicts cystic fibrosis airway cells that have lost the ability to regulate ASL volume following infection with GFP-labeled viruses that inhibit intracellular Ca2+ signaling by depleting extracellular ATP.
  2. Gender differences in cystic fibrosis lung disease: Females suffer more severely with cystic fibrosis than their male counterparts, resulting in a significantly shorter lifespan. This gender difference becomes apparent after puberty. Accordingly, we are currently investigating whether estrogens affect Ca2+ signaling and ASL homeostasis. Figure 4 shows an example of simultaneous Fura-2 imaging (as a marker of intracellular Ca2+) and a fusion protein of Estrogen Receptor α (ER α) conjugated to orange fluorescent protein (mOr).
  3. The effects of cigarette smoke on epithelial airway ion transport: Similar to CF, long term tobacco exposure also results in chronic mucus accumulation. We have found that acute tobacco exposure causes a loss of CFTR from the plasma membrane (Fig. 5) and are currently investigating this phenomenon

Techniques Employed:

  • Ca2+ imaging
  • Confocal microscopy
  • Electrophysiology (In vivo nasal potential difference measurements, microelectrodes & Ussing chambers)
  • Fluorescence resonance energy transfer (FRET)
  • Mass Spectrometry
  • Molecular Biology & Real Time (q)PCR
  • Tissue culture
  • Western Blot

Selected Bibliography:

  1. Ghosh A, Coakley RC, Mascenik T, Rowell TR, Davis ES, Rogers K, Webster MJ, Dang H, Herring LE, Sassano MF, Livraghi-Butrico A, Van Buren SK, Graves LM, Herman MA, Randell SH, Alexis NE, Tarran R. Chronic e-cigarette exposure alters the human bronchial epithelial proteome. Am J Respir Crit Care Med. 2018 Jul 1;198(1):67-76. doi: 10.1164/rccm.201710-2033OC. PMID: 29481290. PMCID: PMC6034122.
  2. Moore PJ, Reidel B, Ghosh A, Sesma J, Kesimer M, Tarran R. Cigarette smoke modifies and inactivates SPLUNC1, leading to airway dehydration. FASEB J. 2018 Jun 11:fj201800345R. doi: 10.1096/fj.201800345R. [Epub ahead of print]. PMID: 29890087.
  3. Kim CS, Ahmad S, Wu T, Walton WG, Redinbo MR, Tarran R. SPLUNC1 is an allosteric modulator of the epithelial sodium channel. FASEB J. 2018 May;32(5):2478-2491. doi: 10.1096/fj.201701126R. PMID: 29295861. PMCID: PMC5901381.
  4. Sassano MF, Davis ES, Keating JE, Zorn BT, Kochar TK, Wolfgang MC, Glish GL, Tarran R. Evaluation of e-liquid toxicity using an open-source high-throughput screening assay. PLoS Biol. 2018 Mar 27;16(3):e2003904. doi: 10.1371/journal.pbio.2003904. PMID: 29584716. PMCID: PMC5870948.
  5. Abdullah LH, Coakley R, Webster MJ, Zhu Y, Tarran R, Radicioni G, Kesimer M, Boucher RC, Davis CW, Ribeiro CMP. Mucin production and hydration responses to mucopurulent materials in normal vs. CF airway epithelia. Am J Respir Crit Care Med. 2018 Feb 15;197(4):481-491. doi: 10.1164/rccm.201706-1139OC. PMID: 29099608. PMCID: PMC5821906.
  6. Terryah ST, Fellner RC, Ahmad S, Moore PJ, Reidel B, Sesma JI, Kim CS, Garland AL, Scott DW, Sabater JR, Carpenter J, Randell SH, Kesimer M, Abraham WM, Arendshorst WJ, Tarran R. Evaluation of a SPLUNC1-derived peptide for the treatment of cystic fibrosis lung disease. Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L192-L205. doi: 10.1152/ajplung.00546.2016. PMID: 28982737. PMCID: PMC5866433.
  7. Scott DW, Walker MP, Sesma J, Wu B, Stuhlmiller TJ, Sabater JR, Abraham WM, Crowder TM, Christensen DJ, Tarran R. SPX-101 is a novel epithelial sodium channel-targeted therapeutic for cystic fibrosis that restores mucus transport. Am J Respir Crit Care Med. 2017 Sep 15;196(6):734-744. doi: 10.1164/rccm.201612-2445OC. PMID: 28481660.
  8. Matson BC, Pierce SL, Espenschied ST, Holle E, Sweatt IH, Davis ES, Tarran R, Young SL, Kohout TA, van Duin M, Caron KM. Adrenomedullin improves fertility and promotes pinopodes and cell junctions in the peri-implantation endometrium. Biol Reprod. 2017 Sep 1;97(3):466-477. doi: 10.1093/biolre/iox101. PMID: 29025060.
  9. Schick SF, Blount BC, Jacob P Rd, Saliba NA, Bernert JT, El Hellani A, Jatlow P, Pappas RS, Wang L, Foulds J, Ghosh A, Hecht SS, Gomez JC, Martin JR, Mesaros C, Srivastava S, St Helen G, Tarran R, Lorkiewicz PK, Blair IA, Kimmel HL, Doerschuk CM, Benowitz NL, Bhatnagar A. Biomarkers of exposure to new and emerging tobacco delivery products. Am J Physiol Lung Cell Mol Physiol. 2017 Sep 1;313(3):L425-L452. doi: 10.1152/ajplung.00343.2016. PMID: 28522563. PMCID: PMC5626373.
  10. Davis ES, Sassano MF, Goodell H, Tarran R. E-liquid autofluorescence can be used as a marker of vaping deposition and third-hand vape exposure. Sci Rep. 2017 Aug 7;7(1):7459. doi: 10.1038/s41598-017-07862-w. PMID: 28785072. PMCID: PMC5547159.
  11. Rowell TR, Reeber SL, Lee SL, Harris RA, Nethery RC, Herring AH, Glish GL, Tarran R. Flavored e-cigarette liquids reduce proliferation and viability in the CALU3 airway epithelial cell line. Am J Physiol Lung Cell Mol Physiol. 2017 Jul 1;313(1):L52-L66. doi: 10.1152/ajplung.00392.2016. PMID: 28428175. PMCID: PMC5538872.
  12. Sassano MF, Ghosh A, Tarran R. Tobacco smoke constituents trigger cytoplasmic calcium release. Appl In Vitro Toxicol. 2017 Jun 1;3(2):193-198. doi: 10.1089/aivt.2016.0039. PMID: 28620626. PMCID: PMC5469188.
  13. Ghosh A, Abdelwahab SH, Reeber SL, Reidel B, Marklew AJ, Garrison AJ, Lee S, Dang H, Herring AH, Glish GL, Kesimer M, Tarran R. Little cigars are more toxic than cigarettes and uniquely change the airway gene and protein expression. Sci Rep. 2017 Apr 27;7:46239. doi: 10.1038/srep46239. PMID: 28447619. PMCID: PMC5406835.
  14. Ghosh A, Nethery RC, Herring AH, Tarran R. Flavored little cigar smoke induces cytotoxicity and apoptosis in airway epithelia. Cell Death Discov. 2017 Apr 24;3:17019. doi: 10.1038/cddiscovery.2017.19. PMID: 28496992. PMCID: PMC5402522.
  15. Wu T, Huang J, Moore PJ, Little MS, Walton WG, Fellner RC, Alexis NE, Peter Di Y, Redinbo MR, Tilley SL, Tarran R. Identification of BPIFA1/SPLUNC1 as an epithelium-derived smooth muscle relaxing factor. Nat Commun. 2017 Feb 6;8:14118. doi: 10.1038/ncomms14118. PMID: 28165446; PMCID: PMC5303822.
  16. Fellner RC, Terryah ST, Tarran R. Inhaled protein/peptide-based therapies for respiratory disease. Mol Cell Pediatr. 2016 Dec;3(1):16. doi: 10.1186/s40348-016-0044-8. PMID: 27098663. PMCID: PMC4839019.
  17. Garnett JP, Kalsi KK, Sobotta M, Bearham J, Carr G, Powell J, Brodlie M, Ward C, Tarran R, Baines DL. Hyperglycaemia and Pseudomonas aeruginosa acidify cystic fibrosis airway surface liquid by elevating epithelial monocarboxylate transporter 2 dependent lactate-H+ secretion. Sci Rep. 2016 Nov 29;6:37955. doi: 10.1038/srep37955. PMID: 27897253. PMCID: PMC5126573.
  18. Ahmad S, Tyrrell J, Walton WG, Tripathy A, Redinbo MR, Tarran R. Short palate, lung, and nasal epithelial clone 1 has antimicrobial and antibiofilm activities against the Burkholderia cepacia complex. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6003-12. doi: 10.1128/AAC.00975-16. PMID: 27458217. PMCID: PMC5038247.
  19. Sun Y, Hu W, Yu X, Liu Z, Tarran R, Ravid K, Huang P. Actinin-1 binds to the C-terminus of A2B adenosine receptor (A2BAR) and enhances A2BAR cell-surface expression. Biochem J. 2016 Jul 15;473(14):2179-86. doi: 10.1042/BCJ20160272. PMID: 27208173.
  20. Watson MJ, Lee SL, Marklew AJ, Gilmore RC, Gentzsch M, Sassano MF, Gray MA, Tarran R. The cystic fibrosis transmembrane conductance regulator (CFTR) uses its C-terminus to regulate the A2B adenosine receptor. Sci Rep. 2016 Jun 9;6:27390. doi: 10.1038/srep27390. PMID: 27278076. PMCID: PMC4899698.
  21. Walton WG, Ahmad S, Little MS, Kim CS, Tyrrell J, Lin Q, Di YP, Tarran R, Redinbo MR. Structural features essential to the antimicrobial functions of human SPLUNC1. Biochemistry. 2016 May 31;55(21):2979-91. doi: 10.1021/acs.biochem.6b00271. PMID: 27145151. PMCID: PMC4887393.
  22. Turner MJ, Saint-Criq V, Patel W, Ibrahim SH, Verdon B, Ward C, Garnett JP, Tarran R, Cann MJ, Gray MA. Hypercapnia modulates cAMP signalling and cystic fibrosis transmembrane conductance regulator-dependent anion and fluid secretion in airway epithelia. J Physiol. 2016 Mar 15;594(6):1643-61. doi: 10.1113/JP271309. PMID: 26574187. PMCID: PMC4799982.
  23. Behrsing H, Raabe H, Manuppello J, Bombick B, Curren R, Sullivan K, Sethi S, Phipps R, Tesfaigzi Y, Yan S, D’Ruiz C, Tarran R, Constant S, Phillips G, Gaça M, Hayden P, Cao X, Mathis C, Hoeng J, Braun A, Hill E. Assessment of in vitro COPD models for tobacco regulatory science: Workshop proceedings, conclusions and paths forward for in vitro model use. Altern Lab Anim. 2016 May;44(2):129-66. PMID: 27256455.
  24. Rowell TR, Tarran R. Will chronic e-cigarette use cause lung disease? Am J Physiol Lung Cell Mol Physiol. 2015 Dec 15;309(12):L1398-409. doi: 10.1152/ajplung.00272.2015. PMID: 26408554. PMCID: PMC4683316.
  25. Manzanares D, Krick S, Baumlin N, Dennis JS, Tyrrell J, Tarran R, Salathe M. Airway surface dehydration by transforming growth factor β (TGF-β) in cystic fibrosis is due to decreased function of a voltage-dependent potassium channel and can be rescued by the drug pirfenidone. J Biol Chem. 2015 Oct 16;290(42):25710-6. doi: 10.1074/jbc.M115.670885. PMID: 26338706. PMCID: PMC4646213.
  26. Choi HC, Kim CS, Tarran R. Automated acquisition and analysis of airway surface liquid height by confocal microscopy. Am J Physiol Lung Cell Mol Physiol. 2015 Jul 15;309(2):L109-18. doi: 10.1152/ajplung.00027.2015. PMID: 26001773. PMCID: PMC4504972.
  27. Xu X, Balsiger R, Tyrrell J, Boyaka PN, Tarran R, Cormet-Boyaka E. Cigarette smoke exposure reveals a novel role for the MEK/ERK1/2 MAPK pathway in regulation of CFTR. Biochim Biophys Acta. 2015 Jun;1850(6):1224-32. doi: 10.1016/j.bbagen.2015.02.004. PMID: 25697727. PMCID: PMC4398641.
  28. Tyrrell J, Qian X, Freire J, Tarran R. Roflumilast combined with adenosine increases mucosal hydration in human airway epithelial cultures after cigarette smoke exposure. Am J Physiol Lung Cell Mol Physiol. 2015 May 15;308(10):L1068-77. doi: 10.1152/ajplung.00395.2014. PMID: 25795727. PMCID: PMC4437008.
  29. Åstrand AB, Hemmerling M, Root J, Wingren C, Pesic J, Johansson E, Garland AL, Ghosh A, Tarran R. Linking increased airway hydration, ciliary beating, and mucociliary clearance through ENaC inhibition. Am J Physiol Lung Cell Mol Physiol. 2015 Jan 1;308(1):L22-32. doi: 10.1152/ajplung.00163.2014. PMID: 25361567. PMCID: PMC4281700.
  30. Ghosh A, Boucher RC, Tarran R. Airway hydration and COPD. Cell Mol Life Sci. 2015;72(19):3637-52. PMID: 26068443. PMCID: PMC4567929.
  31. Rasmussen JE, Sheridan JT, Polk W, Davies CM, Tarran R. Cigarette smoke-induced Ca2+ release leads to cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction. J Biol Chem. 2014 Mar 14;289(11):7671-81. doi: 10.1074/jbc.M113.545137. Epub 2014 Jan 21. PMID: 24448802; PMCID: PMC3953278.
  32. Garland AL, Walton WG, Coakley RD, Tan CD, Gilmore RC, Hobbs CA, Tripathy A, Clunes LA, Bencharit S, Stutts MJ, Betts L, Redinbo MR, Tarran R. Molecular basis for pH-dependent mucosal dehydration in cystic fibrosis airways. Proc Natl Acad Sci U S A. 2013 Oct 1;110(40):15973-8. doi: 10.1073/pnas.1311999110. Epub 2013 Sep 16. PMID: 24043776; PMCID: PMC3791714.
  33. Clunes LA, Davies CM, Coakley RD, Aleksandrov AA, Henderson AG, Zeman KL, Worthington EN, Gentzsch M, Kreda SM, Cholon D, Bennett WD, Riordan JR, Boucher RC, Tarran R. Cigarette smoke exposure induces CFTR internalization and insolubility, leading to airway surface liquid dehydration. FASEB J. 2012 Feb;26(2):533-45. doi: 10.1096/fj.11-192377. Epub 2011 Oct 11. PMID: 21990373; PMCID: PMC3290447.
  34. Garcia-Caballero A, Rasmussen JE, Gaillard E, Watson MJ, Olsen JC, Donaldson SH, Stutts MJ, Tarran R. SPLUNC1 regulates airway surface liquid volume by protecting ENaC from proteolytic cleavage. Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):11412-7. doi: 10.1073/pnas.0903609106. Epub 2009 Jun 18. PMID: 19541605; PMCID: PMC2708735. Erratum in: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):15091.
  35. Coakley RD, Sun H, Clunes LA, Rasmussen JE, Stackhouse JR, Okada SF, Fricks I, Young SL, Tarran R. 17beta-Estradiol inhibits Ca2+-dependent homeostasis of airway surface liquid volume in human cystic fibrosis airway epithelia. J Clin Invest. 2008 Dec;118(12):4025-35. doi: 10.1172/JCI33893. Epub 2008 Nov 20. PMID: 19033671; PMCID: PMC2582929.

Dr. Tarran has several open post-doctoral positions. Please contact him at

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Robert Tarran, PhD