Information

Related Research Units

Respiratory Diseases Research

Research Overview

The major goal of the Park Laboratory is to understand how fundamental functions of extracellular matrix (ECM) components modulate the pathogenesis of infectious and inflammatory disease. Historically known for its structural roles, the ECM is now known to regulate many molecular and cellular mechanisms. The Park laboratory has found that microbial pathogens exploit the syndecan family of cell surface heparan sulfate proteoglycans to enhance their virulence in vivo. Several major bacterial pathogens induce syndecan shedding from the cell surface through specific virulence factors. Shed syndecan ectodomains inhibit several host defense mechanisms, shifting the balance of host-pathogen interaction to favor pathogenesis over eradication. The Park Laboratory has also found that syndecans modulate the progression and outcome of non-infectious inflammatory disease. Here, syndecans regulate inflammatory mediators and cells to confine, attenuate, or resolve inflammatory processes. These data suggest that syndecans assure the correct and adequate functioning of inflammation, but that certain pathogens have adapted or evolved to exploit these mechanisms to promote their pathogenesis.

Research Background

Pyong Woo Park received a PhD from Washington University in St. Louis, Missouri and completed a fellowship at Children’s Hospital Boston and Harvard Medical School.

Publications

  1. Sulfated motifs in heparan sulfate inhibit Streptococcus pneumoniae adhesion onto fibronectin and attenuate corneal infection. Proteoglycan Res. 2023 Jul 01; 1(3). View Abstract
  2. Coreceptor functions of cell surface heparan sulfate proteoglycans. Am J Physiol Cell Physiol. 2022 05 01; 322(5):C896-C912. View Abstract
  3. Role of HSPGs in Systemic Bacterial Infections. Methods Mol Biol. 2022; 2303:605-625. View Abstract
  4. CD138 expression is a molecular signature but not a developmental requirement for ROR?t+ NKT17 cells. JCI Insight. 2021 09 22; 6(18). View Abstract
  5. Syndecan-1 Promotes Streptococcus pneumoniae Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils. mBio. 2020 12 08; 11(6). View Abstract
  6. A stem cell reporter based platform to identify and target drug resistant stem cells in myeloid leukemia. Nat Commun. 2020 11 26; 11(1):5998. View Abstract
  7. Host syndecan-1 promotes listeriosis by inhibiting intravascular neutrophil extracellular traps. PLoS Pathog. 2020 05; 16(5):e1008497. View Abstract
  8. Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure. Sci Transl Med. 2020 03 18; 12(535). View Abstract
  9. Characterization of the zinc metalloprotease of Streptococcus suis serotype 2. Vet Res. 2018 Oct 29; 49(1):109. View Abstract
  10. Syndecan-1 Regulates Psoriasiform Dermatitis by Controlling Homeostasis of IL-17-Producing ?d T Cells. J Immunol. 2018 09 15; 201(6):1651-1661. View Abstract
  11. Introduction to the thematic mini-review series on "Matrix biology in lung health and disease". Matrix Biol. 2018 11; 73:1-5. View Abstract
  12. Glycobiology of syndecan-1 in bacterial infections. Biochem Soc Trans. 2018 04 17; 46(2):371-377. View Abstract
  13. Isolation and functional analysis of syndecans. Methods Cell Biol. 2018; 143:317-333. View Abstract
  14. Syndecan-1 limits the progression of liver injury and promotes liver repair in acetaminophen-induced liver injury in mice. Hepatology. 2017 11; 66(5):1601-1615. View Abstract
  15. Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock. Shock. 2017 09; 48(3):340-345. View Abstract
  16. CD138 mediates selection of mature plasma cells by regulating their survival. Blood. 2017 05 18; 129(20):2749-2759. View Abstract
  17. EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay. J Exp Med. 2017 03 06; 214(3):623-637. View Abstract
  18. Cell surface-anchored syndecan-1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis. J Cell Mol Med. 2017 01; 21(1):13-25. View Abstract
  19. Shedding of Syndecan-1/CXCL1 Complexes by Matrix Metalloproteinase 7 Functions as an Epithelial Checkpoint of Neutrophil Activation. Am J Respir Cell Mol Biol. 2016 08; 55(2):243-51. View Abstract
  20. Glycosaminoglycans and infection. Front Biosci (Landmark Ed). 2016 06 01; 21(6):1260-77. View Abstract
  21. Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice. Shock. 2015 Nov; 44(5):452-7. View Abstract
  22. Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels. J Cell Biol. 2015 Sep 28; 210(7):1199-211. View Abstract
  23. 2-O-Sulfated Domains in Syndecan-1 Heparan Sulfate Inhibit Neutrophil Cathelicidin and Promote Staphylococcus aureus Corneal Infection. J Biol Chem. 2015 Jun 26; 290(26):16157-67. View Abstract
  24. Role of glycosaminoglycans in infectious disease. Methods Mol Biol. 2015; 1229:567-85. View Abstract
  25. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013 Sep; 40(3):195-202. View Abstract
  26. Syndecan-1 and heparanase: potential markers for activity evaluation and differential diagnosis of Crohn's disease. Inflamm Bowel Dis. 2013 Apr; 19(5):1025-33. View Abstract
  27. The endothelial glycocalyx in syndecan-1 deficient mice. Microvasc Res. 2013 May; 87:83-91. View Abstract
  28. Syndecan 1 plays a novel role in enteral glutamine's gut-protective effects of the postischemic gut. Shock. 2012 Jul; 38(1):57-62. View Abstract
  29. Shedding of cell membrane-bound proteoglycans. Methods Mol Biol. 2012; 836:291-305. View Abstract
  30. Syndecan-1 displays a protective role in aortic aneurysm formation by modulating T cell-mediated responses. Arterioscler Thromb Vasc Biol. 2012 Feb; 32(2):386-96. View Abstract
  31. Molecular functions of syndecan-1 in disease. Matrix Biol. 2012 Jan; 31(1):3-16. View Abstract
  32. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6(8):e23530. View Abstract
  33. Dual protective mechanisms of matrix metalloproteinases 2 and 9 in immune defense against Streptococcus pneumoniae. J Immunol. 2011 Jun 01; 186(11):6427-36. View Abstract
  34. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011 Jun; 112(6):1289-95. View Abstract
  35. Syndecan-1 promotes Staphylococcus aureus corneal infection by counteracting neutrophil-mediated host defense. J Biol Chem. 2011 Feb 04; 286(5):3288-97. View Abstract
  36. Molecular and cellular mechanisms of ectodomain shedding. Anat Rec (Hoboken). 2010 Jun; 293(6):925-37. View Abstract
  37. Proteoglycans in host-pathogen interactions: molecular mechanisms and therapeutic implications. Expert Rev Mol Med. 2010 Feb 01; 12:e5. View Abstract
  38. Diverse functions of glycosaminoglycans in infectious diseases. Prog Mol Biol Transl Sci. 2010; 93:373-94. View Abstract
  39. Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines. Blood. 2009 Oct 01; 114(14):3033-43. View Abstract
  40. Staphylococcus aureus beta-toxin induces lung injury through syndecan-1. Am J Pathol. 2009 Feb; 174(2):509-18. View Abstract
  41. Microbial subversion of heparan sulfate proteoglycans. Mol Cells. 2008 Nov 30; 26(5):415-26. View Abstract
  42. Alpha-toxin facilitates the generation of CXC chemokine gradients and stimulates neutrophil homing in Staphylococcus aureus pneumonia. J Infect Dis. 2008 Nov 15; 198(10):1529-35. View Abstract
  43. Syndecan-1 ectodomain shedding is regulated by the small GTPase Rab5. J Biol Chem. 2008 Dec 19; 283(51):35435-44. View Abstract
  44. Syndecan-1 is an in vivo suppressor of Gram-positive toxic shock. J Biol Chem. 2008 Jul 18; 283(29):19895-903. View Abstract
  45. Stimulus-dependent impairment of the neutrophil oxidative burst response in lactoferrin-deficient mice. Am J Pathol. 2008 Apr; 172(4):1019-29. View Abstract
  46. Heparan sulfate and syndecan-1 are essential in maintaining murine and human intestinal epithelial barrier function. J Clin Invest. 2008 Jan; 118(1):229-38. View Abstract
  47. Molecular and cellular mechanisms of syndecans in tissue injury and inflammation. Mol Cells. 2007 Oct 31; 24(2):153-66. View Abstract
  48. Increase in soluble CD138 in bronchoalveolar lavage fluid of multicentric Castleman's disease. Respirology. 2007 Jan; 12(1):140-3. View Abstract
  49. Streptococcus pneumoniae sheds syndecan-1 ectodomains through ZmpC, a metalloproteinase virulence factor. J Biol Chem. 2007 Jan 05; 282(1):159-67. View Abstract
  50. Syndecan-1 expression in epithelial cells is induced by transforming growth factor beta through a PKA-dependent pathway. J Biol Chem. 2006 Aug 25; 281(34):24365-74. View Abstract
  51. Synthesis of syndecan-1 by skeletal muscle cells is an early response to infection with Trichinella spiralis but is not essential for nurse cell development. Infect Immun. 2006 Mar; 74(3):1941-3. View Abstract
  52. Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis. Infect Immun. 2005 Dec; 73(12):7914-21. View Abstract
  53. Blocking of monocyte chemoattractant protein-1 during tubulointerstitial nephritis resulted in delayed neutrophil clearance. Am J Pathol. 2005 Sep; 167(3):637-49. View Abstract
  54. Endogenous attenuation of allergic lung inflammation by syndecan-1. J Immunol. 2005 May 01; 174(9):5758-65. View Abstract
  55. Protamine sulfate reduces the susceptibility of thermally injured mice to Pseudomonas aeruginosa infection. J Surg Res. 2005 Jan; 123(1):109-17. View Abstract
  56. Syndecan-1 in Microbial Pathogenesis, Host Defense, and Inflammation. Trends in Glycoscience and Glycotechnology. 2005; 17(98):271-284. View Abstract
  57. The N-terminal A domain of fibronectin-binding proteins A and B promotes adhesion of Staphylococcus aureus to elastin. J Biol Chem. 2004 Sep 10; 279(37):38433-40. View Abstract
  58. Activation of syndecan-1 ectodomain shedding by Staphylococcus aureus alpha-toxin and beta-toxin. J Biol Chem. 2004 Jan 02; 279(1):251-8. View Abstract
  59. Matrilysin shedding of syndecan-1 regulates chemokine mobilization and transepithelial efflux of neutrophils in acute lung injury. Cell. 2002 Nov 27; 111(5):635-46. View Abstract
  60. Unlocking the secrets of syndecans: transgenic organisms as a potential key. Glycoconj J. 2002 May-Jun; 19(4-5):295-304. View Abstract
  61. The elastin-binding protein of Staphylococcus aureus (EbpS) is expressed at the cell surface as an integral membrane protein and not as a cell wall-associated protein. J Biol Chem. 2002 Jan 04; 277(1):243-50. View Abstract
  62. Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence. Nature. 2001 May 03; 411(6833):98-102. View Abstract
  63. Cell surface heparan sulfate proteoglycans: selective regulators of ligand-receptor encounters. J Biol Chem. 2000 Sep 29; 275(39):29923-6. View Abstract
  64. Shedding of syndecan-1 and -4 ectodomains is regulated by multiple signaling pathways and mediated by a TIMP-3-sensitive metalloproteinase. J Cell Biol. 2000 Feb 21; 148(4):811-24. View Abstract
  65. Syndecan-1 shedding is enhanced by LasA, a secreted virulence factor of Pseudomonas aeruginosa. J Biol Chem. 2000 Feb 04; 275(5):3057-64. View Abstract
  66. Characterization of the elastin binding domain in the cell-surface 25-kDa elastin-binding protein of staphylococcus aureus (EbpS). J Biol Chem. 1999 Jan 29; 274(5):2845-50. View Abstract
  67. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999; 68:729-77. View Abstract
  68. Molecular cloning and expression of the gene for elastin-binding protein (ebpS) in Staphylococcus aureus. J Biol Chem. 1996 Jun 28; 271(26):15803-9. View Abstract
  69. Lysozyme binds to elastin and protects elastin from elastase-mediated degradation. J Invest Dermatol. 1996 May; 106(5):1075-80. View Abstract
  70. Binding and degradation of elastin by the staphylolytic enzyme lysostaphin. Int J Biochem Cell Biol. 1995 Feb; 27(2):139-46. View Abstract
  71. Binding of elastin to Staphylococcus aureus. J Biol Chem. 1991 Dec 05; 266(34):23399-406. View Abstract
  72. Characterization of a putative clone for the 67-kilodalton elastin/laminin receptor suggests that it encodes a cytoplasmic protein rather than a cell surface receptor. Biochemistry. 1991 Apr 02; 30(13):3346-50. View Abstract
  73. Polyclonal antibodies to tropoelastin and the specific detection and measurement of tropoelastin in vitro. Connect Tissue Res. 1991; 25(3-4):265-79. View Abstract
  74. Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival. Surgery. 1989 Feb; 105(2 Pt 1):218-23. View Abstract

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