The main research focus in the Chai laboratory is a novel “extracellular membrane-associated serine protease proteolytic activation and action network”, involving the glycosylphosphatidylinositol (GPI)-anchored prostasin (PRSS8), the type-II transmembrane hepsin (TMPRSS1) and matriptase (PRSS14), and the urokinase-type plasminogen activator (uPA) with its GPI-anchored plasma membrane receptor uPAR. This novel serine protease activation and action network has direct impacts on the cellular signals mediated by two major classes of membrane receptors, the receptor tyrosine kinases (RTKs) represented by the epidermal growth factor receptor (EGFR/ErbB1/Her-1) and the G-protein-coupled receptors (GPCRs) such as the protease-activated receptor 2 (PAR-2). Ultimately, this extracellular membrane-associated serine protease activation and action network is essential for maintaining epithelial homeostasis but is also implicated in the pathophysiology of many epithelial cancers. Currently we are investigating the proteolytic actions of these extracellular membrane-associated serine proteases on all members of the ErbB family RTKs using breast cancer cells as the study subject.
- Chen LM, Chang M, Dai Y, Chai KX, Dyrskjøt L, Sanchez-Carbayo M, Szarvas T, Zwarthoff EC, Lokeshwar 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. External Validation of a Multiplex Urinary Protein Panel for the Detection of Bladder Cancer in a Multicenter Cohort. Cancer Epidemiol Biomarkers Prev. 2014 Jun 11. [Epub ahead of print]
- Gomes-Giacoia E, Miyake M, Goodison S, Sriharan A, Zhang G, You L, Egan JO, Rhode PR, Parker AS, Chai KX, Wong HC, Rosser CJ. Intravesical ALT-803 and BCG treatment reduces tumor burden in a carcinogen induced bladder cancer rat model; a role for cytokine production and NK cell expansion. PLoS One. 2014 Jun 4;9(6):e96705.
- D’Angelo RC, Liu XW, Najy AJ, Jung YS, Won J, Chai KX, Fridman R, Kim HR. TIMP-1 via TWIST1 Induces EMT Phenotypes in Human Breast Epithelial Cells. Mol Cancer Res. 2014 Jun 3. [Epub ahead of print]
- Wood MP, Cole AL, Eade CR, Chen LM, Chai KX, Cole AM. The HIV-1 gp41 ectodomain is cleaved by matriptase to produce a chemotactic peptide that acts through FPR2. Immunology. 2014 Jul;142(3):474-83.
- Chen LM, Nergard JC, Ni L, Rosser CJ, Chai KX. Long-term exposure to cigarette smoke extract induces hypomethylation at the RUNX3 and IGF2-H19 loci in immortalized human urothelial cells. PLoS One. 2013 May 28;8(5):e65513.
- Fu YY, Nergard JC, Barnette NK, Wang YL, Chai KX, Chen LM. Proteasome inhibition augments cigarette smoke-induced GM-CSF expression in trophoblast cells via the epidermal growth factor receptor. PLoS One. 2012;7(8):e43042.
- Xu Z, Chen YW, Battu A, Wilder P, Weber D, Yu W, Mackerell AD, Chen LM, Chai KX, Johnson MD, Lin CY. Targeting zymogen activation to control the matriptase-prostasin proteolytic cascade. J Med Chem. 2011 Nov 10;54(21):7567-78. PMID: 21966950
- Martellini JA, Cole AL, Svoboda P, Stuchlik O, Chen LM, Chai KX, Gangrade BK, Sørensen OE, Pohl J, Cole AM. HIV-1 enhancing effect of prostatic acid phosphatase peptides is reduced in human seminal plasma. PLoS One. 2011 Jan 20;6(1):e16285. PMID: 21283773
- Chen YW, Wang JK, Chou FP, Chen CY, Rorke EA, Chen LM, Chai KX, Eckert RL, Johnson MD, Lin CY. Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 (HAI-1) during epidermal differentiation. J Biol Chem. 2010 Oct 8;285(41):31755-62. PMID: 20696767
- Gao L, Smith RS, Chen LM, Chai KX, Chao L, Chao J. Tissue kallikrein promotes prostate cancer cell migration and invasion via a protease-activated receptor-1-dependent signaling pathway. Biol Chem. 2010 Jul;391(7):803-12. PMID: 20482314
- Chen M, Chen LM, Lin CY, Chai KX. Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor. Mol Cell Biochem. 2010 Apr;337(1-2):259-66. PMID: 19911255
- Fu YY, Gao WL, Chen M, Chai KX, Wang YL, Chen LM. Prostasin regulates human placental trophoblast cell proliferation via the epidermal growth factor receptor signaling pathway. Hum Reprod. 2010 Mar;25(3):623-32. PMID: 20089521
- Wang C, Ma L, Chen LM, Chai KX, Su M. Scanning calorimetric detections of multiple DNA biomarkers contained in complex fluids. Anal Chem. 2010 Mar 1;82(5):1838-43. PMID: 20146470
- Ma XJ, Fu YY, Li YX, Chen LM, Chai K, Wang YL. Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells. Histochem Cell Biol. 2009 Dec;132(6):639-46. PMID: 19847458
- Chen LM, Hatfield ML, Fu YY, Chai KX. Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells. Prostate. 2009 Dec 1;69(16):1790-801. PMID: 19670249
- Chen LM, Verity NJ, Chai KX. Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT). BMC Cancer. 2009 Oct 22;9:377. PMID: 19849847