ABOUT THE RESEARCHER

OVERVIEW

The major goal of the Park Laboratory is to understand how components of the extracellular matrix (ECM) modulate the pathogenesis of infectious and non-infectious inflammatory diseases, with a particular focus on the role of proteoglycans, glycosaminoglycans, and elastin in these processes. Historically known for its structural roles, the ECM is now known to regulate many cellular and physiological processes.

Dr. Park and his colleagues have found that several major bacterial pathogens (e.g., Pseudomonas aeruginosa, Staphylococcus aureus, Streptococcus pneumoniae) subvert the syndecan family of cell surface heparan sulfate proteoglycans to enhance their virulence in vivo. These bacterial pathogens stimulate syndecan shedding from the cell surface through specific virulence factors. Syndecan ectodomains bind to and inhibit several host defense factors and immune cells, modulating the host environment to favor pathogenesis over eradication. These findings indicate that exploitation of syndecan shedding is an important pathogenic mechanism and suggest possible approaches to therapy.

The Park Laboratory has also found that syndecan shedding is activated in non-infectious inflammatory diseases. Here, syndecan ectodomains modulate inflammatory mediators and cells to attenuate inflammatory tissue injury. In sum, these data suggest that syndecan shedding is an important mechanism that assures the correct and adequate functioning of inflammation, but that certain pathogens have adapted or evolved to exploit this mechanism to promote their pathogenesis. On-going projects are focused on defining the molecular and cellular details of these mechanisms.

BACKGROUND

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

PUBLICATIONS

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  1. Syndecan-1 Promotes Streptococcus pneumoniae Corneal Infection by Facilitating the Assembly of Adhesive Fibronectin Fibrils. mBio. 2020 12 08; 11(6). View abstract
  2. 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
  3. Host syndecan-1 promotes listeriosis by inhibiting intravascular neutrophil extracellular traps. PLoS Pathog. 2020 05; 16(5):e1008497. View abstract
  4. Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure. Sci Transl Med. 2020 03 18; 12(535). View abstract
  5. Characterization of the zinc metalloprotease of Streptococcus suis serotype 2. Vet Res. 2018 Oct 29; 49(1):109. View abstract
  6. 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
  7. Introduction to the thematic mini-review series on "Matrix biology in lung health and disease". Matrix Biol. 2018 11; 73:1-5. View abstract
  8. Glycobiology of syndecan-1 in bacterial infections. Biochem Soc Trans. 2018 04 17; 46(2):371-377. View abstract
  9. Isolation and functional analysis of syndecans. Methods Cell Biol. 2018; 143:317-333. View abstract
  10. 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
  11. Loss of Syndecan-1 Abrogates the Pulmonary Protective Phenotype Induced by Plasma After Hemorrhagic Shock. Shock. 2017 09; 48(3):340-345. View abstract
  12. CD138 mediates selection of mature plasma cells by regulating their survival. Blood. 2017 05 18; 129(20):2749-2759. View abstract
  13. EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay. J Exp Med. 2017 03 06; 214(3):623-637. View abstract
  14. 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
  15. 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
  16. Glycosaminoglycans and infection. Front Biosci (Landmark Ed). 2016 06 01; 21:1260-77. View abstract
  17. Plasma-Mediated Gut Protection After Hemorrhagic Shock is Lessened in Syndecan-1-/- Mice. Shock. 2015 Nov; 44(5):452-7. View abstract
  18. Transmembrane proteoglycans control stretch-activated channels to set cytosolic calcium levels. J Cell Biol. 2015 Sep 28; 210(7):1199-211. View abstract
  19. 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
  20. Role of glycosaminoglycans in infectious disease. Methods Mol Biol. 2015; 1229:567-85. View abstract
  21. 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
  22. 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
  23. The endothelial glycocalyx in syndecan-1 deficient mice. Microvasc Res. 2013 May; 87:83-91. View abstract
  24. 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
  25. Shedding of cell membrane-bound proteoglycans. Methods Mol Biol. 2012; 836:291-305. View abstract
  26. 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
  27. Molecular functions of syndecan-1 in disease. Matrix Biol. 2012 Jan; 31(1):3-16. View abstract
  28. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6(8):e23530. View abstract
  29. 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
  30. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth Analg. 2011 Jun; 112(6):1289-95. View abstract
  31. 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
  32. Molecular and cellular mechanisms of ectodomain shedding. Anat Rec (Hoboken). 2010 Jun; 293(6):925-37. View abstract
  33. Proteoglycans in host-pathogen interactions: molecular mechanisms and therapeutic implications. Expert Rev Mol Med. 2010 Feb 01; 12:e5. View abstract
  34. Diverse functions of glycosaminoglycans in infectious diseases. Prog Mol Biol Transl Sci. 2010; 93:373-94. View abstract
  35. Syndecan-1 shedding facilitates the resolution of neutrophilic inflammation by removing sequestered CXC chemokines. Blood. 2009 Oct 01; 114(14):3033-43. View abstract
  36. Staphylococcus aureus beta-toxin induces lung injury through syndecan-1. Am J Pathol. 2009 Feb; 174(2):509-18. View abstract
  37. Microbial subversion of heparan sulfate proteoglycans. Mol Cells. 2008 Nov 30; 26(5):415-26. View abstract
  38. 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
  39. Syndecan-1 ectodomain shedding is regulated by the small GTPase Rab5. J Biol Chem. 2008 Dec 19; 283(51):35435-44. View abstract
  40. Syndecan-1 is an in vivo suppressor of Gram-positive toxic shock. J Biol Chem. 2008 Jul 18; 283(29):19895-903. View abstract
  41. Stimulus-dependent impairment of the neutrophil oxidative burst response in lactoferrin-deficient mice. Am J Pathol. 2008 Apr; 172(4):1019-29. View abstract
  42. 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
  43. Molecular and cellular mechanisms of syndecans in tissue injury and inflammation. Mol Cells. 2007 Oct 31; 24(2):153-66. View abstract
  44. Increase in soluble CD138 in bronchoalveolar lavage fluid of multicentric Castleman's disease. Respirology. 2007 Jan; 12(1):140-3. View abstract
  45. Streptococcus pneumoniae sheds syndecan-1 ectodomains through ZmpC, a metalloproteinase virulence factor. J Biol Chem. 2007 Jan 05; 282(1):159-67. View abstract
  46. 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
  47. 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
  48. Syndecan 1 shedding contributes to Pseudomonas aeruginosa sepsis. Infect Immun. 2005 Dec; 73(12):7914-21. View abstract
  49. 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
  50. Endogenous attenuation of allergic lung inflammation by syndecan-1. J Immunol. 2005 May 01; 174(9):5758-65. View abstract
  51. Protamine sulfate reduces the susceptibility of thermally injured mice to Pseudomonas aeruginosa infection. J Surg Res. 2005 Jan; 123(1):109-17. View abstract
  52. Syndecan-1 in Microbial Pathogenesis, Host Defense, and Inflammation. Trends in Glycoscience and Glycotechnology. 2005; 17(98):271-284. View abstract
  53. 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
  54. 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
  55. 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
  56. Unlocking the secrets of syndecans: transgenic organisms as a potential key. Glycoconj J. 2002 May-Jun; 19(4-5):295-304. View abstract
  57. 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
  58. Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence. Nature. 2001 May 03; 411(6833):98-102. View abstract
  59. Cell surface heparan sulfate proteoglycans: selective regulators of ligand-receptor encounters. J Biol Chem. 2000 Sep 29; 275(39):29923-6. View abstract
  60. 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
  61. 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
  62. 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
  63. Functions of cell surface heparan sulfate proteoglycans. Annu Rev Biochem. 1999; 68:729-77. View abstract
  64. 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
  65. Lysozyme binds to elastin and protects elastin from elastase-mediated degradation. J Invest Dermatol. 1996 May; 106(5):1075-80. View abstract
  66. Binding and degradation of elastin by the staphylolytic enzyme lysostaphin. Int J Biochem Cell Biol. 1995 Feb; 27(2):139-46. View abstract
  67. Binding of elastin to Staphylococcus aureus. J Biol Chem. 1991 Dec 05; 266(34):23399-406. View abstract
  68. 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
  69. 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
  70. Trophic factors from pancreatic islets in combined hepatocyte-islet allografts enhance hepatocellular survival. Surgery. 1989 Feb; 105(2 Pt 1):218-23. View abstract