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Last Name

Matthew S Walters

InstitutionUniversity of Oklahoma Health Sciences Center
DepartmentMedicine Pulmonary
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    Collapse Biography 
    Collapse education and training
    University of Liverpool, Liverpool, UKBSc (1st Class Honors)2000Genetics
    University of Leeds, Leeds, UKPhD2004Molecular Virology

    Collapse Overview 
    Collapse overview
    The major focus of my laboratory is to understand the processes that regulate lung regeneration during health and in response to environmental insult, including cigarette smoke. Chronic obstructive pulmonary disease (COPD) is the 3rd leading cause of death in the US, with an estimated 90% of cases caused by cigarette smoking. Currently there is no cure for COPD and therapeutic options to treat the disease are limited. The earliest cigarette smoking-induced changes relevant to the pathogenesis of COPD occur in the airway epithelium, a multi-cellular tissue that covers the luminal surface of the conducting airways of the lung. The airway epithelium functions as a barrier to protect the lung from pathogens and harmful environmental factors via the action of specialized cells including basal, secretory and ciliated cells. Basal cells (BC) are the stem/progenitor population of the human airway epithelium that differentiate into secretory and ciliated cells during normal epithelial turnover and in response to injury. This process is highly coordinated and is regulated by multiple signaling pathways and cellular interactions between BC and other cell types in the lung microenvironment. Cigarette smoking alters the normal differentiation response of BC, resulting in epithelial remodeling which negatively impacts the overall function of the airway epithelium and health of the lung. Our goal is to identify key pathways and define critical cell interactions that regulate the stem/progenitor phenotype of BC within the lung microenvironment during health and disease. To achieve this goal, our lab uses different molecular and cellular approaches, including in vitro differentiation models to mimic the in vivo airway epithelium and targeting of specific genes/pathways via lentivirus-mediated gene transfer/knockdown and CRISPR-directed genome editing. Combined, these approaches will help identify pathways and cellular interactions that regulate differentiation of BC providing novel targets for developing new therapeutic and/or regenerative medicine approaches for the treatment of smoking-induced lung disease, including COPD.

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    Collapse selected publications
    Publications listed below are automatically derived from MEDLINE/PubMed and other sources, which might result in incorrect or missing publications. Faculty can login to make corrections and additions.
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    1. Zuo WL, Shenoy SA, Li S, O'Beirne SL, Strulovici-Barel Y, Leopold PL, Wang G, Staudt MR, Walters MS, Mason C, Kaner RJ, Mezey JG, Crystal RG. Ontogeny and Biology of Human Small Airway Epithelial Club Cells. Am J Respir Crit Care Med. 2018 Dec 01; 198(11):1375-1388. PMID: 29874100.
      View in: PubMed
    2. Zhang H, Yang J, Walters MS, Staudt MR, Strulovici-Barel Y, Salit J, Mezey JG, Leopold PL, Crystal RG. Mandatory role of HMGA1 in human airway epithelial normal differentiation and post-injury regeneration. Oncotarget. 2018 Mar 06; 9(18):14324-14337. PMID: 29581847.
      View in: PubMed
    3. Wang G, Zhou H, Strulovici-Barel Y, Al-Hijji M, Ou X, Salit J, Walters MS, Staudt MR, Kaner RJ, Crystal RG. Role of OSGIN1 in mediating smoking-induced autophagy in the human airway epithelium. Autophagy. 2017 Jul 03; 13(7):1205-1220. PMID: 28548877.
      View in: PubMed
    4. Gomi K, Tang Y, Arbelaez V, Crystal RG, Walters MS. Endothelial Cell Mediated Promotion of Ciliated Cell Differentiation of Human Airway Basal Cells via Insulin and Insulin-Like Growth Factor 1 Receptor Mediated Signaling. Stem Cell Rev. 2017 04; 13(2):309-317. PMID: 28050756.
      View in: PubMed
    5. Walters MS, Salit J, Ju JH, Staudt MR, Kaner RJ, Rogalski AM, Sodeinde TB, Rahim R, Strulovici-Barel Y, Mezey JG, Almulla AM, Sattar H, Mahmoud M, Crystal RG. Waterpipe smoking induces epigenetic changes in the small airway epithelium. PLoS One. 2017; 12(3):e0171112. PMID: 28273093.
      View in: PubMed
    6. Strulovici-Barel Y, Shaykhiev R, Salit J, Deeb RS, Krause A, Kaner RJ, Vincent TL, Agosto-Perez F, Wang G, Hollmann C, Shanmugam V, Almulla AM, Sattar H, Mahmoud M, Mezey JG, Gross SS, Staudt MR, Walters MS, Crystal RG. Pulmonary Abnormalities in Young, Light-Use Waterpipe (Hookah) Smokers. Am J Respir Crit Care Med. 2016 09 01; 194(5):587-95. PMID: 27007171.
      View in: PubMed
    7. Gomi K, Staudt MR, Salit J, Kaner RJ, Heldrich J, Rogalski AM, Arbelaez V, Crystal RG, Walters MS. JAG1-Mediated Notch Signaling Regulates Secretory Cell Differentiation of the Human Airway Epithelium. Stem Cell Rev. 2016 08; 12(4):454-63. PMID: 27216293.
      View in: PubMed
    8. Zhou H, Brekman A, Zuo WL, Ou X, Shaykhiev R, Agosto-Perez FJ, Wang R, Walters MS, Salit J, Strulovici-Barel Y, Staudt MR, Kaner RJ, Mezey JG, Crystal RG, Wang G. POU2AF1 Functions in the Human Airway Epithelium To Regulate Expression of Host Defense Genes. J Immunol. 2016 Apr 01; 196(7):3159-67. PMID: 26927796; PMCID: PMC4799774 [Available on 04/01/17].
    9. Deeb RS, Walters MS, Strulovici-Barel Y, Chen Q, Gross SS, Crystal RG. Smoking-Associated Disordering of the Airway Basal Stem/Progenitor Cell Metabotype. Am J Respir Cell Mol Biol. 2016 Feb; 54(2):231-40. PMID: 26161876; PMCID: PMC4821042 [Available on 02/01/17].
    10. Ding BS, Gomi K, Rafii S, Crystal RG, Walters MS. Endothelial MMP14 is required for endothelial-dependent growth support of human airway basal cells. J Cell Sci. 2015 Aug 15; 128(16):2983-8. PMID: 26116571; PMCID: PMC4541042.
    11. Gomi K, Arbelaez V, Crystal RG, Walters MS. Activation of NOTCH1 or NOTCH3 signaling skews human airway basal cell differentiation toward a secretory pathway. PLoS One. 2015; 10(2):e0116507. PMID: 25700162; PMCID: PMC4336283.
    12. Durgan J, Tao G, Walters MS, Florey O, Schmidt A, Arbelaez V, Rosen N, Crystal RG, Hall A. SOS1 and Ras regulate epithelial tight junction formation in the human airway through EMP1. EMBO Rep. 2015 Jan; 16(1):87-96. PMID: 25394671; PMCID: PMC4304732.
    13. Brekman A, Walters MS, Tilley AE, Crystal RG. FOXJ1 prevents cilia growth inhibition by cigarette smoke in human airway epithelium in vitro. Am J Respir Cell Mol Biol. 2014 Nov; 51(5):688-700. PMID: 24828273; PMCID: PMC4224080.
    14. Tilley AE, Walters MS, Shaykhiev R, Crystal RG. Cilia dysfunction in lung disease. Annu Rev Physiol. 2015; 77:379-406. PMID: 25386990.
      View in: PubMed
    15. Staudt MR, Buro-Auriemma LJ, Walters MS, Salit J, Vincent T, Shaykhiev R, Mezey JG, Tilley AE, Kaner RJ, Ho MW, Crystal RG. Airway Basal stem/progenitor cells have diminished capacity to regenerate airway epithelium in chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2014 Oct 15; 190(8):955-8. PMID: 25317467; PMCID: PMC4299582.
    16. Walters MS, De BP, Salit J, Buro-Auriemma LJ, Wilson T, Rogalski AM, Lief L, Hackett NR, Staudt MR, Tilley AE, Harvey BG, Kaner RJ, Mezey JG, Ashbridge B, Moore MA, Crystal RG. Smoking accelerates aging of the small airway epithelium. Respir Res. 2014 Sep 24; 15:94. PMID: 25248511; PMCID: PMC4189169.
    17. Feng B, Jiao P, Helou Y, Li Y, He Q, Walters MS, Salomon A, Xu H. Mitogen-activated protein kinase phosphatase 3 (MKP-3)-deficient mice are resistant to diet-induced obesity. Diabetes. 2014 Sep; 63(9):2924-34. PMID: 24722245; PMCID: PMC4141371.
    18. Ryan DM, Vincent TL, Salit J, Walters MS, Agosto-Perez F, Shaykhiev R, Strulovici-Barel Y, Downey RJ, Buro-Auriemma LJ, Staudt MR, Hackett NR, Mezey JG, Crystal RG. Smoking dysregulates the human airway basal cell transcriptome at COPD risk locus 19q13.2. PLoS One. 2014; 9(2):e88051. PMID: 24498427; PMCID: PMC3912203.
    19. Walters MS, Gomi K, Ashbridge B, Moore MA, Arbelaez V, Heldrich J, Ding BS, Rafii S, Staudt MR, Crystal RG. Generation of a human airway epithelium derived basal cell line with multipotent differentiation capacity. Respir Res. 2013 Dec 03; 14:135. PMID: 24298994; PMCID: PMC3907041.
    20. Buro-Auriemma LJ, Salit J, Hackett NR, Walters MS, Strulovici-Barel Y, Staudt MR, Fuller J, Mahmoud M, Stevenson CS, Hilton H, Ho MW, Crystal RG. Cigarette smoking induces small airway epithelial epigenetic changes with corresponding modulation of gene expression. Hum Mol Genet. 2013 Dec 01; 22(23):4726-38. PMID: 23842454; PMCID: PMC3888123.
    21. Didon L, Zwick RK, Chao IW, Walters MS, Wang R, Hackett NR, Crystal RG. RFX3 modulation of FOXJ1 regulation of cilia genes in the human airway epithelium. Respir Res. 2013 Jul 03; 14:70. PMID: 23822649; PMCID: PMC3710277.
    22. Curradi G, Walters MS, Ding BS, Rafii S, Hackett NR, Crystal RG. Airway basal cell vascular endothelial growth factor-mediated cross-talk regulates endothelial cell-dependent growth support of human airway basal cells. Cell Mol Life Sci. 2012 Jul; 69(13):2217-31. PMID: 22382924; PMCID: PMC3633460.
    23. Hackett NR, Shaykhiev R, Walters MS, Wang R, Zwick RK, Ferris B, Witover B, Salit J, Crystal RG. The human airway epithelial basal cell transcriptome. PLoS One. 2011 May 04; 6(5):e18378. PMID: 21572528; PMCID: PMC3087716.
    24. Walters MS, Kinchington PR, Banfield BW, Silverstein S. Hyperphosphorylation of histone deacetylase 2 by alphaherpesvirus US3 kinases. J Virol. 2010 Oct; 84(19):9666-76. PMID: 20660201; PMCID: PMC2937806.
    25. Walters MS, Kyratsous CA, Silverstein SJ. The RING finger domain of Varicella-Zoster virus ORF61p has E3 ubiquitin ligase activity that is essential for efficient autoubiquitination and dispersion of Sp100-containing nuclear bodies. J Virol. 2010 Jul; 84(13):6861-5. PMID: 20392849; PMCID: PMC2903287.
    26. Mueller NH, Walters MS, Marcus RA, Graf LL, Prenni J, Gilden D, Silverstein SJ, Cohrs RJ. Identification of phosphorylated residues on varicella-zoster virus immediate-early protein ORF63. J Gen Virol. 2010 May; 91(Pt 5):1133-7. PMID: 20089801; PMCID: PMC2888152.
    27. Walters MS, Erazo A, Kinchington PR, Silverstein S. Histone deacetylases 1 and 2 are phosphorylated at novel sites during varicella-zoster virus infection. J Virol. 2009 Nov; 83(22):11502-13. PMID: 19740981; PMCID: PMC2772673.
    28. Kyratsous CA, Walters MS, Panagiotidis CA, Silverstein SJ. Complementation of a herpes simplex virus ICP0 null mutant by varicella-zoster virus ORF61p. J Virol. 2009 Oct; 83(20):10637-43. PMID: 19656893; PMCID: PMC2753114.
    29. Walters MS, Kyratsous CA, Wan S, Silverstein S. Nuclear import of the varicella-zoster virus latency-associated protein ORF63 in primary neurons requires expression of the lytic protein ORF61 and occurs in a proteasome-dependent manner. J Virol. 2008 Sep; 82(17):8673-86. PMID: 18562514; PMCID: PMC2519623.
    30. Z├╝rcher T, Yates PJ, Daly J, Sahasrabudhe A, Walters M, Dash L, Tisdale M, McKimm-Breschkin JL. Mutations conferring zanamivir resistance in human influenza virus N2 neuraminidases compromise virus fitness and are not stably maintained in vitro. J Antimicrob Chemother. 2006 Oct; 58(4):723-32. PMID: 16891631.
      View in: PubMed
    31. Wakenshaw L, Walters MS, Whitehouse A. The Herpesvirus saimiri replication and transcription activator acts synergistically with CCAAT enhancer binding protein alpha to activate the DNA polymerase promoter. J Virol. 2005 Nov; 79(21):13548-60. PMID: 16227275; PMCID: PMC1262591.
    32. Walters MS, Hall KT, Whitehouse A. The herpesvirus saimiri Rta gene autostimulates via binding to a non-consensus response element. J Gen Virol. 2005 Mar; 86(Pt 3):581-7. PMID: 15722517.
      View in: PubMed
    33. Walters MS, Hall KT, Whitehouse A. The herpesvirus saimiri open reading frame (ORF) 50 (Rta) protein contains an at hook required for binding to the ORF 50 response element in delayed-early promoters. J Virol. 2004 May; 78(9):4936-42. PMID: 15078979; PMCID: PMC387665.
    34. Goodwin DJ, Walters MS, and Whitehouse A. Gene Regulation in the Prototype gamma-2 Herpesvirus. Current Topics in Virology. 2003; 3:33-52.
    35. Liloglou T, Walters M, Maloney P, Youngson J, Field JK. A T2517C polymorphism in the GSTM4 gene is associated with risk of developing lung cancer. Lung Cancer. 2002 Aug; 37(2):143-6. PMID: 12140136.
      View in: PubMed
    36. Goodwin DJ, Walters MS, Smith PG, Thurau M, Fickenscher H, Whitehouse A. Herpesvirus saimiri open reading frame 50 (Rta) protein reactivates the lytic replication cycle in a persistently infected A549 cell line. J Virol. 2001 Apr; 75(8):4008-13. PMID: 11264393; PMCID: PMC114895.
    37. Barnett JM, Cadman A, Gor D, Dempsey M, Walters M, Candlin A, Tisdale M, Morley PJ, Owens IJ, Fenton RJ, Lewis AP, Claas EC, Rimmelzwaan GF, De Groot R, Osterhaus AD. Zanamivir susceptibility monitoring and characterization of influenza virus clinical isolates obtained during phase II clinical efficacy studies. Antimicrob Agents Chemother. 2000 Jan; 44(1):78-87. PMID: 10602727; PMCID: PMC89632.
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