Scott H Randell, PhD

Associate Professor

Specialty Areas

Airway Epithelial Stem Cells, Airway Innate Immunity and Response to Injury, mRNA regulation

Research Focus

Identification of airway epithelial stem cells. Dr. Randell’s goals are to identify and isolate airway epithelial stem cells and to understand molecular mechanisms regulating airway epithelial cell proliferation and fate decisions.Research in Dr. Randell’s laboratory is currently focused on five areas where a greater knowledge of basic cell biology can be applied towards overcoming clinical lung disease problems:

  • Micro RNA Regulation of Human Airway Epithelial Phenotype- ARRA Award. The Randell Laboratory comprehensively determines the miRNA repertoire of human airway epithelial cells will tests the ability of miRNAs to alter cell structure and function. These studies will create a valuable database and will suggest novel treatments for lung disease.
  • Innate immunity in the airway. Dr Randell aims to better understand molecular mechanisms regulating airway epithelial adaptation to injury and chronic infection and to understand the relationship of adaptation to the pathogenesis of airway disease.
  • Post-lung transplant ischemia reperfusion injury and bronchiolitis obliterans syndrome. The Randell Laboratory is also examining basic mechanisms of lung injury relevant to transplantation and bronchiolitis obliterans syndrome, the leading cause of lung allograft failure.
  • Dr. Scott Randell also directs the UNC CF Center Tissue Procurement and Cell Culture Core, which provides primary and passaged human airway and alveolar epithelial cells, lung microvascular endothelial cells, media and expertise to UNC CF Center investigators and collaborators. Our facility has become a nationally and internationally recognized resource whose services are sought for collaboration, contract research, and training by academics, non-profit organizations, biotech and the pharmaceutical industry.
Figure 1. X-Y plane confocal microscopy of cultured human airway epithelial cells expressing green and red fluorescent protein.
Figure 1. X-Y plane confocal microscopy of cultured human airway epithelial cells expressing green and red fluorescent protein.
Figure 2. Human bronchial epithelial cells in culture, fixed with perflurocarbon OsO4 and prepared for high resolution light microscopy.
Figure 2. Human bronchial epithelial cells in culture, fixed with perflurocarbon OsO4 and prepared for high resolution light microscopy.
Figure 3. Frozen section of a human cystic fibrosis airway excised during lung transplantation, stained for mucus. Note the adhesion between the mucus in the lumen and the airway wall.
Figure 3. Frozen section of a human cystic fibrosis airway excised during lung transplantation, stained for mucus. Note the adhesion between the mucus in the lumen and the airway wall.

Staff

Teresa Mascenik

Teresa Mascenik
Research Specialist

Tuong Nguyen

Tuong Nguyen
Research Technician

Rhianna Lee

Rhianna Lee
Graduate Student

Selected Bibliography

  1. Smeekens JM, Immormino RM, Balogh PA, Randell SH, Kulis MD, Moran TP. Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway. Clin Exp Allergy. 2019 Aug 24. doi: 10.1111/cea.13486. [Epub ahead of print]. PMID: 31444814.
  2. Marozkina N, Bosch J, Cotton C, Smith L, Seckler J, Zaman K, Rehman S, Periasamy A, Gaston H, Altawallbeh G, Davis M, Jones DR, Schilz R, Randell SH, Gaston B. Cyclic compression increases F508 Del CFTR expression in ciliated human airway epithelium. Am J Physiol Lung Cell Mol Physiol. 2019 Aug 1;317(2):L247-L258. doi: 10.1152/ajplung.00020.2019. PMID: 31116581.
  3. Parker MM, Hao Y, Guo F, Pham B, Chase R, Platig J, Cho MH, Hersh CP, Thannickal VJ, Crapo J, Washko G, Randell SH, Silverman EK, San José Estépar R, Zhou X, Castaldi PJ. Identification of an emphysema-associated genetic variant near TGFB2 with regulatory effects in lung fibroblasts. Elife. 2019 Jul 25;8. doi: 10.7554/eLife.42720. PMID: 31343404. PMCID: PMC6693893.
  4. Barrios J, Kho AT, Aven L, Mitchel JA, Park JA, Randell SH, Miller LA, Tantisira KG, Ai X. Pulmonary Neuroendocrine Cells Secrete GABA to Induce Goblet Cell Hyperplasia in Primate Models. Am J Respir Cell Mol Biol. 2019 Jun;60(6):687-694. doi: 10.1165/rcmb.2018-0179OC. PMID: 30571139. PMCID: PMC6543741.
  5. Chen G, Ribeiro CMP, Sun L, Okuda K, Kato T, Gilmore RC, Martino MB, Dang H, Abzhanova A, Lin JM, Hull-Ryde EA, Volmer AS, Randell SH, Livraghi-Butrico A, Deng Y, Scherer PE, Stripp BR, O’Neal WK, Boucher RC. XBP1S Regulates MUC5B in a Promoter Variant-Dependent Pathway in IPF Airway Epithelia. Am J Respir Crit Care Med. 2019 Apr 11. doi: 10.1164/rccm.201810-1972OC. [Epub ahead of print]. PMID: 30973754.
  6. Okuda K, Chen G, Subramani DB, Wolf M, Gilmore RC, Kato T, Radicioni G, Kesimer M, Chua M, Dang H, Livraghi-Butrico A, Ehre C, Doerschuk CM, Randell SH, Matsui H, Nagase T, O’Neal WK, Boucher RC. Localization of Secretory Mucins MUC5AC and MUC5B in Normal/Healthy Human Airways. Am J Respir Crit Care Med. 2019 Mar 15;199(6):715-727. doi: 10.1164/rccm.201804-0734OC. PMID: 30352166. PMCID: PMC6423099.
  7. Berical A, Lee RE, Randell SH, Hawkins F. Challenges Facing Airway Epithelial Cell-Based Therapy for Cystic Fibrosis. Front Pharmacol. 2019 Feb 8;10:74. doi: 10.3389/fphar.2019.00074. PMID: 30800069. PMCID: PMC6376457.
  8. Khatri A, Kraft BD, Tata PR, Randell SH, Piantadosi CA, Pendergast AM. ABL kinase inhibition promotes lung regeneration through expansion of an SCGB1A1+ SPC+ cell population following bacterial pneumonia. Proc Natl Acad Sci U S A. 2019 Jan 29;116(5):1603-1612. doi: 10.1073/pnas.1816030116. PMID: 30655340. PMCID: PMC6358689.
  9. Panganiban RA, Sun M, Dahlin A, Park HR, Kan M, Himes BE, Mitchel JA, Iribarren C, Jorgenson E, Randell SH, Israel E, Tantisira K, Shore S, Park JA, Weiss ST, Wu AC, Lu Q. A functional splice variant associated with decreased asthma risk abolishes the ability of gasdermin B to induce epithelial cell pyroptosis. J Allergy Clin Immunol. 2018 Nov;142(5):1469-1478.e2. doi: 10.1016/j.jaci.2017.11.040. PMID: 29330013. PMCID: PMC6037620.
  10. Gupta R, Radicioni G, Abdelwahab S, Dang H, Carpenter J, Chua M, Mieczkowski PA, Sheridan J, Randell SH, Kesimer M. Intercellular Communication between Airway Epithelial Cells is Mediated by Exosome-Like Vesicles. Am J Respir Cell Mol Biol. 2019 Feb;60(2):209-220. doi: 10.1165/rcmb.2018-0156OC. PMID: 30230353. PMCID: PMC6376407.
  11. 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.
  12. Gillen AE, Yang R, Cotton CU, Perez A, Randell SH, Leir SH, Harris A. Molecular characterization of gene regulatory networks in primary human tracheal and bronchial epithelial cells. J Cyst Fibros. 2018 Jul;17(4):444-453. doi: 10.1016/j.jcf.2018.01.009. PMID: 29459038. PMCID: PMC6026051.
  13. Porrello A, Leslie PL, Harrison EB, Gorentla BK, Kattula S, Ghosh SK, Azam SH, Holtzhausen A, Chao YL, Hayward MC, Waugh TA, Bae S, Godfrey V, Randell SH, Oderup C, Makowski L, Weiss J, Wilkerson MD, Hayes DN, Earp HS, Baldwin AS, Wolberg AS, Pecot CV. Factor XIIIA-expressing inflammatory monocytes promote lung squamous cancer through fibrin cross-linking. Nat Commun. 2018 May 18;9(1):1988. doi: 10.1038/s41467-018-04355-w. PMID: 29777108. PMCID: PMC5959879.
  14. 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.
  15. Yu D, Saini Y, Chen G, Ghio AJ, Dang H, Burns KA, Wang Y, Davis RM, Randell SH, Esther Jr CR, Paulsen F, Boucher RC. Loss of β epithelial sodium channel function in meibomian glands produces pseudohypoaldosteronism 1-like ocular disease in mice. Am J Pathol. 2018 Jan;188(1):95-110.doi: 10.1016/j.ajpath.2017.09.016. PMID: 29107074. PMCID: PMC5745530.
  16. Keating JE, Minges JT, Randell SH, Glish GL. Paper spray mass spectrometry for high-throughput quantification of nicotine and cotinine. Anal Methods. 2018;10(1):46-50. doi: 10.1039/C7AY02204B. PMID: 29568335. PMCID: PMC5858713.
  17. Randell SH, Zeldin DC. A slippery cause of a slimy problem: Mucin induction by an esterified lipid. Am J Respir Cell Mol Biol. 2017 Dec;57(6):633-634. doi: 10.1165/rcmb.2017-0275ED. PMID: 29192828. PMCID: PMC5800897.
  18. Snyder RJ, Hussain S, Tucker CJ, Randell SH, Garantziotis S. Impaired Ciliogenesis in differentiating human bronchial epithelia exposed to non-Cytotoxic doses of multi-walled carbon Nanotubes. Part Fibre Toxicol. 2017 Nov 13;14(1):44. doi: 10.1186/s12989-017-0225-1. PMID: 29132433. PMCID: PMC5683528.
  19. Venkataraman A, Blackwell JW, Funkhouser WK, Birchard KR, Beamer SE, Simmons WT, Randell SH, Egan TM. Beware cold agglutinins in organ donors! Ex vivo lung perfusion from an uncontrolled donation after circulatory-determination-of-death donor with a cold agglutinin: A case report. Transplant Proc. 2017 Sep;49(7):1678-1681. doi: 10.1016/j.transproceed.2017.04.004. PMID: 28838463. PMCID: PMC6034983.
  20. Fossum SL, Mutolo MJ, Tugores A, Ghosh S, Randell SH, Jones LC, Leir SH, Harris A. Ets homologous factor (EHF) has critical roles in epithelial dysfunction in airway disease. J Biol Chem. 2017 Jun 30;292(26):10938-10949. doi: 10.1074/jbc.M117.775304. PMID: 28461336. PMCID: PMC5491778.
  21. Xiang H, Yuan L, Gao X, Alexander PB, Lopez O, Lau C, Ding Y, Chong M, Sun T, Chen R, Liu SQ, Wu H, Wan Y, Randell SH, Li QJ, Wang XF. UHRF1 is required for basal stem cell proliferation in response to airway injury. Cell Discov. 2017 Jun 13;3:17019. doi: 10.1038/celldisc.2017.19. PMID: 28626588. PMCID: PMC5468773.
  22. Gentzsch M, Boyles SE, Cheluvaraju C, Chaudhry IG, Quinney NL, Cho C, Dang H, Liu X, Schlegel R, Randell SH. Pharmacological rescue of conditionally reprogrammed cystic fibrosis bronchial epithelial cells. Am J Respir Cell Mol Biol. 2017 May;56(5):568-574. doi: 10.1165/rcmb.2016-0276MA. PMID: 27983869. PMCID: PMC5449492.
  23. Anthony SJ, Gilardi K, Menachery VD, Goldstein T, Ssebide B, Mbabazi R, Navarrete-Macias I, Liang E, Wells H, Hicks A, Petrosov A, Byarugaba DK, Debbink K, Dinnon KH, Scobey T, Randell SH, Yount BL, Cranfield M, Johnson CK, Baric RS, Lipkin WI, Mazet JA. Further evidence for bats as the evolutionary source of Middle East respiratory syndrome coronavirus. MBio. 2017 Apr 4;8(2). doi: 10.1128/mBio.00373-17. PMID: 28377531. PMCID: PMC5380844.
  24. Liu X, Krawczyk E, Suprynowicz FA, Palechor-Ceron N, Yuan H, Dakic A, Simic V, Zheng YL, Sripadhan P, Chen C, Lu J, Hou TW, Choudhury S, Kallakury B, Tang DG, Darling T, Thangapazham R, Timofeeva O, Dritschilo A, Randell SH, Albanese C, Agarwal S, Schlegel R. Conditional reprogramming and long-term expansion of normal and tumor cells from human biospecimens. Nat Protoc. 2017 Feb;12(2):439-451. doi: 10.1038/nprot.2016.174. PMID: 28125105. PMCID: PMC6195120.
  25. Mitchel JA, Antoniak S, Lee JH, Kim SH, McGill M, Kasahara DI, Randell SH, Israel E, Shore SA, Mackman N, Park JA. IL-13 augments compressive stress-induced tissue factor expression in human airway epithelial cells. Am J Respir Cell Mol Biol. 2016 Apr;54(4):524-31. doi: 10.1165/rcmb.2015-0252OC. PMID: 26407210. PMCID: PMC4821058.
  26. Gentzsch M, Ren HY, Houck SA, Quinney NL, Cholon DM, Sopha P, Chaudhry IG, Das J, Dokholyan NV, Randell SH, Cyr DM. Restoration of R117H CFTR folding and function in human airway cells through combination treatment with VX-809 and VX-770. Am J Physiol Lung Cell Mol Physiol. 2016 Sep 1;311(3):L550-9. doi: 10.1152/ajplung.00186. PMID: 27402691. PMCID: PMC5142211.
  27. Wagner DE, Cardoso WV, Gilpin SE, Majka S, Ott H, Randell SH, Thébaud B, Waddell T, Weiss DJ; ATS Subcommittee on Stem Cells and Cell Therapies. An Official American Thoracic Society Workshop Report 2015. Stem cells and cell therapies in lung biology and diseases. Ann Am Thorac Soc. 2016 Aug;13(8):S259-78. doi: 10.1513/AnnalsATS.201606-466ST. PMID: 27509163.
  28. Yu D, Davis RM, Aita M, Burns KA, Clapp PW, Gilmore RC, Chua M, O’Neal WK, Schlegel R, Randell SH, C Boucher R. Characterization of rat meibomian gland ion and fluid transport. Invest Ophthalmol Vis Sci. 2016 Apr 1;57(4):2328-43. doi: 10.1167/iovs.15-17945. PMID: 27127933. PMCID: PMC4855829.
  29. Menachery VD, Yount BL Jr, Sims AC, Debbink K, Agnihothram SS, Gralinski LE, Graham RL, Scobey T, Plante JA, Royal SR, Swanstrom J, Sheahan TP, Pickles RJ, Corti D, Randell SH, Lanzavecchia A, Marasco WA, Baric RS. SARS-like WIV1-CoV poised for human emergence. Proc Natl Acad Sci U S A. 2016 Mar 15;113(11):3048-53. doi: 10.1073/pnas.1517719113. PMID: 26976607. PMCID: PMC4801244.
  30. Park JA, Mitchel JA, Qazvini NT, Kim JH, Park CY, Butler JP, Israel E, Randell SH, Shore SA, Drazen JM, Fredberg JJ. Compressive stress causes an unjamming transition and an epithelial-mesenchymal transition in the airway epithelium in asthma. Ann Am Thorac Soc. 2016 Mar;13 Suppl 1:S102. doi: 10.1513/AnnalsATS.201506-382MG. PMID: 27027941. PMCID: PMC5015726.
  31. Turner MJ, Matthes E, Billet A, Ferguson AJ, Thomas DY, Randell SH, Ostrowski LE, Abbott-Banner K, Hanrahan JW. The dual phosphodiesterase 3 and 4 inhibitor RPL554 stimulates CFTR and ciliary beating in primary cultures of bronchial epithelia. Am J Physiol Lung Cell Mol Physiol. 2016 Jan 1;310(1):L59-70. doi: 10.1152/ajplung.00324.2015. PMID: 26545902.
  32. Park JA, Kim JH, Bi D, Mitchel JA, Qazvini NT, Tantisira K, Park CY, McGill M, Kim SH, Gweon B, Notbohm J, Steward R Jr, Burger S, Randell SH, Kho AT, Tambe DT, Hardin C, Shore SA, Israel E, Weitz DA, Tschumperlin DJ, Henske EP, Weiss ST, Manning ML, Butler JP, Drazen JM, Fredberg JJ. Unjamming and cell shape in the asthmatic airway epithelium. Nat Mater. 2015 Oct;14(10):1040-8. doi: 10.1038/nmat4357. PMID: 26237129. PMCID: PMC4666305.
  33. Evans ES, Hackney AC, McMurray RG, Randell SH, Muss HB, Deal AM, Battaglini CL. Impact of acute intermittent exercise on natural killer cells in breast cancer survivors. Integr Cancer Ther. 2015 Sep;14(5):436-45. doi: 10.1177/1534735415580681. PMID: 25873292.
  34. Fritzsching B, Zhou-Suckow Z, Trojanek JB, Schubert SC, Schatterny J, Hirtz S, Agrawal R, Muley T, Kahn N, Sticht C, Gunkel N, Welte T, Randell SH, Länger F, Schnabel P, Herth FJ, Mall MA. Hypoxic epithelial necrosis triggers neutrophilic inflammation via IL-1 receptor signaling in cystic fibrosis lung disease. Am J Respir Crit Care Med. 2015 Apr 15;191(8):902-13. doi: 10.1164/rccm.201409-1610OC. PubMed PMID: 25607238; PubMed Central PMCID: PMC4435455.
  35. Chand HS, Montano G, Huang X, Randell SH, Mebratu Y, Petersen H, Tesfaigzi Y. A genetic variant of p53 restricts the mucous secretory phenotype by regulating SPDEF and Bcl-2 expression. Nat Commun. 2014 Nov 27;5:5567. doi: 10.1038/ncomms6567. PubMed PMID: 25429397; PubMed Central PMCID: PMC4247165.
  36. Hogan BL, Barkauskas CE, Chapman HA, Epstein JA, Jain R, Hsia CC, Niklason L, Calle E, Le A, Randell SH, Rock J, Snitow M, Krummel M, Stripp BR, Vu T, White ES, Whitsett JA, Morrisey EE. Repair and regeneration of the respiratory system: complexity, plasticity, and mechanisms of lung stem cell function. Cell Stem Cell. 2014 Aug 7;15(2):123-38. doi: 10.1016/j.stem.2014.07.012. Review. PubMed PMID: 25105578; PubMed Central PMCID: PMC4212493.
  37. Cholon DM, Quinney NL, Fulcher ML, Esther CR Jr, Das J, Dokholyan NV, Randell SH, Boucher RC, Gentzsch M. Potentiator ivacaftor abrogates pharmacological correction of ΔF508 CFTR in cystic fibrosis. Sci Transl Med. 2014 Jul 23;6(246):246ra96. doi: 10.1126/scitranslmed.3008680. PubMed PMID: 25101886; PubMed Central PMCID: PMC4272825.
  38. Chen G, Korfhagen TR, Karp CL, Impey S, Xu Y, Randell SH, Kitzmiller J, Maeda Y, Haitchi HM, Sridharan A, Senft AP, Whitsett JA. Foxa3 induces goblet cell metaplasia and inhibits innate antiviral immunity. Am J Respir Crit Care Med. 2014 Feb 1;189(3):301-13. doi: 10.1164/rccm.201306-1181OC. PubMed PMID: 24392884; PubMed Central PMCID: PMC3977731.
Scott H. Randell, PhD. Director