We are investigating the impact of cigarette smoking on human health. Cigarette smoke compromises lung epithelium integrity and causes lung inflammation, which eventually leads to chronic lung diseases such as emphysema and bronchitis. It has been known for many years that chronic inflammation is associated with epithelial carcinogenesis. Smokers with airway inflammation have a higher risk of lung cancer compared with smokers without chronic inflammation. Targeting the inflammatory mediators has been investigated as a therapeutic strategy for decreasing the incidence and spread of cancers. Prostasin is an epithelial glycosylphosphatidylinositol-anchored membrane serine protease. Prostasin has been implicated for mechanistic roles in maintaining the integrity of the epithelium via regulating the tight junctions at the cell-cell contacts, in taming innate epithelial inflammation via attenuating the expression of inducible nitric oxide synthase, and in inhibiting tumor cell invasion and metastasis. Our research is focused on elucidating the mechanisms of prostasin’s roles during inflammation and cancer development and progression.

Recent Publications

  1. Chen L-M, Chang M, Dai Y, Chai KX, Dyrskjøt L, Sanchez-Cabayo M, Szarvas T, Zwarthoff EC, Lokeswhar V, Jeronimo C, Parker AS, Ross S, Borre M, Orntoft TF, Jaeger T, Beukers W, Lopez LE, Henrique R, Young PR, Urquidi V, Goodison S, Rosser CJ. (2014) External Validation of a Multiplex Urinary Protein Panel for the Detection of Bladder Cancer in a Multicenter Cohort. Cancer Epidemiol Biomarkers Prev. Jun 11 [Epub ahead of print]
  2. Wood MP, Cole AL, Eade CR, Chen L-M, Chai KX, Cole AM. (2014) The HIV-1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2. Immunology 142(3):474-83.
  3. Chen L-M, Nergard JC, Ni L, Rosser CJ, Chai KX. (2013) Long-term exposure to cigarette smoke extract induces hypomethylation at the RUNX3 and IGF2-H19 loci in immortalized human urothelial cells. PLoS One 8(5):e65513.
  4. Fu YY, Nergard JC, Barnette NK, Wang YL, Chai KX, and Chen L-M. (2012) Effect of cigarette smoke extract on the expression of granulocyte-macrophage colony-stimulating factor expression in a normal human trophoblast cell line. PLoS One 7(8):e43042.
  5. Xu Z, Chen YW, Battu A, Wilder P, Weber D, Yu W, Mackerell AD, Chen L-M, Chai KX, Johnson MD, Lin CY. (2011). Targeting zymogen activation to control the matriptase-prostasin proteolytic cascade. J Med Chem 2011 Nov 10;54(21):7567-78. Epub 2011 Oct 12. PMID: 21966950
  6. Martellini JA, Cole AL, Svoboda P, Stuchlik O, Chen L-M, Chai KX, Gangrade BK, Sørensen OE, Pohl J, Cole AM (2011). HIV-1 Enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma. PLoS One 6(1):e16285.
  7. Chen YW, Chou FP, Chen CY, Rorke EA, Wang JK, Chen L-M, Chai KX, Eckert RL, Johnson MD, and Lin CY. (2010). Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation. J Biol Chem 285(41):31755-62.
  8. Gao L, Smith RS, Chen L-M, Chai KX, Chao L. Chao J. (2010) Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway. Biol Chem. 391(7):803-12.
  9. Wang C, Ma L, Chen L-M, Chai KX, and Su M. (2010) Scanning calorimetric detections of multiple DNA biomarkers contained in complex fluids. Anal Chem. 82(5):1838-43.
  10. Fu YY, Gao WL, Chen M, Chai KX, Wang YL, and Chen L-M. (2010) Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway. Hum Reprod. 25(3):623-32.
  11. Chen M, Chen L-M, Lin CY, and Chai KX. (2010) Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor. Mol. Cell. Biochem. 337(1-2):259-66.
  12. Chen L-M, Verity NJ, and Chai KX. (2009) Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT). BMC Cancer. 9:377.
  13. Ma XJ, Fu YY, Li YX, Chen L-M, Chai KX, Wang YL. (2009) Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells. Histochem. Cell Biol. 132(6):639-46.
  14. Chen L-M, Hatfield ML, Fu YY, and Chai KX. (2009) Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostate 69(16):1790-801.

Book Chapters

  1. Chao J, Chen L-M, Chai KX. (2013) Prostasin. In The Handbook of Proteolytic Enzymes, 3rd edition. Edited by: Rawlings, N.D. and Guy, S. Elsevier., pp3011-3014
  2. Chao J, Chen L-M, Chai KX. (2013) Human kallikrein-related peptidase 2. In The Handbook of Proteolytic Enzymes, 3rd edition. Edited by: Rawlings, N.D. and Guy, S. Elsevier., pp2762-2765
  3. Chao J, Chai KX, Chen L-M. (2013) Human kallikrein-related peptidase 3, the prostate-specific antigen. In The Handbook of Proteolytic Enzymes, 3rd edition. Edited by: Rawlings, N.D. and Guy, S. Elsevier., pp2765-2768
  4. Chen L-M, Chai KX. (2012) PRSS8 (protease, serine, 8). Atlas Genet Cytogenet Oncol Haematol. 16(9):658-664.

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