NTUBST2023EN

1.    Regulatory mechanism of inflammation and drug development for immunomodulation

Microbial infections and tissue injury can trigger Inflammatory responses, which plays important functions in removing microbes and injured cells, as well as promoting tissue repair. However, uncontrolled inflammation may result in excessive infiltration of immune cells which produce enormous amount of cytokines, leading to cytokine storm, tissue injury and organ dysfunction, such as the acute respiratory distress syndrome (ARDS) in COVID-19. In allergic and autoimmune diseases, continuous inflammation may cause irreversible tissue damages including fibrosis. In addition, inflammatory responses activated in the tumor microenvironment may promote tumorigenesis and suppress antitumor immune responses. 

Research in my lab is focused on elucidating how inflammation is regulated, such as how inflammatory leukocytes (neutrophil, eosinophils, monocytes, etc.) can degrade the extracellular matrix and migrate to the inflamed tissue. We aim to identify key molecules regulating inflammation, which may serve as targets for developing new drugs to regulate inflammation associated with infection, injury, cancer, allergy, and autoimmune diseases. 

2.    Mucosal vaccine development

Most pathogens enter the body via mucosal surfaces, where specialized lymphoid tissues can mount immune responses against the invading microbes, for example, by secreting IgA antibodies to bind and neutralize microorganisms. When designing vaccines, it is desirable to deliver antigens and elicit immune responses at mucosal tissues on the respiratory or gastrointestinal tracts, where infectious agents can be cleared more effectively early during infection. We are aiming to develop novel adjuvants and delivery systems for mucosal vaccines.

1. Lu HY, Huang PH, Lee TW, Chang HW, Chen NY, Zhuang YJ, Yuan TT, Chen CJ*. Enolase-1 is essential for neutrophil recruitment during acute inflammation. 2024; bioRxiv 2024.12.26.630451; doi: https://doi.org/10.1101/2024.12.26.630451
2. Yang JY, Chen KL, Lin YC, Chiu HC, Hsieh HT, Chen CJ*. Ganoderma formosanum polysaccharides enhance antitumor immune responses by downregulating the differentiation of myeloid-derived suppressor cells and tumor-associated macrophages. 2024; bioRxiv 2024.12.23.630057; doi: https://doi.org/10.1101/2024.12.23.630057
3. Huang WC, Chuang CF, Huang YT, Chung IC, Chen ML, Chuang TY, Yang XL, Chou YY, Liu CH, Chen NY, Chen CJ, Yuan TT*. Monoclonal enolase-1 blocking antibody ameliorates pulmonary inflammation and fibrosis. 2023; Respir Res. 24(1):280.
4. Lee HY, Chen CC, Pi CC, Chen CJ. Aspergillus oryzae Fermentation Extract Alleviates Inflammation in Mycoplasma pneumoniae Pneumonia. Molecules 2023; 28(3): 1127.
5. Li CJ, Jiang CL, Chao TL, Lin SY, Tsai YM, Chao CS, Su YT, Chen CJ, Chang SY, Lin FJ, Chang SC. Elicitation of potent neutralizing antibodies in obese mice by ISA 51-adjuvanted SARS-CoV-2 spike RBD-Fc vaccine. Appl Microbiol Biotechnol 2023; 107(9): 2983-95.
6. Huang TR, Jou SB, Chou YJ, Yi PL, Chen CJ, Chang FC*. Interleukin-1 receptor (IL-1R) mediates epilepsy-induced sleep disruption. BMC Neurosci. 2016; 17: 74.
7. Chen CL, Tsai WH, Chen CJ, Pan TM*. Centella asiatica extract protects against amyloid β_1-40-induced neurotoxicity in neuronal cells by activating the antioxidative defence system. J Tradit Complement Med. 2016; 6(4): 362-9.
8. Pi CC, Wang HY, Lu CY, Lu FL, Chen CJ*. Ganoderma  formosanum polysaccharides attenuate Th2 inflammation and airway hyperresponsiveness in a murine model of allergic asthma. SpringerPlus 2014; 3: 297. 
9. Chang YL, Chen TH, Wu YH, Chen GA, Weng TH, Tseng PH, Hsieh SL, Fu SL, Lin CH, Chen CJ, Chu CL, Chio IIC, Mak TW, Chen NJ*. A novel TLR2-triggered signaling crosstalk synergistically intensifies TNF-mediated IL-6 induction. J Cell Mol Med. 2014; 18(7): 1344-57.
10. Pi CC, Chu CL, Lu CY, Zhuang YJ, Wang CL, Yu YH, Wang HY, Lin CC, Chen CJ*. Ganoderma formosanum polysaccharides function as a Th1 adjuvant and stimulate cytotoxic T cell responses in vivo. Vaccine 2014; 32(3): 401-8.
11. Wang JT, Chang LS, Chen CJ, Doong SL, Chang CW, Chen MR*. Glycogen synthase kinase 3 negatively regulates interferon regulatory factor 3 transactivation through phosphorylation at its linker region. Innate Immun. 2014; 20(1): 78-87. 
12. Tzeng HT, Tsai HF, Chyuan IT, Liao HJ, Chen CJ, Chen PJ, Hsu PN*. Tumor necrosis factor-alpha induced by hepatitis B virus core mediating the immune response for hepatitis B viral clearance in mice model. PLoS One 2014; 9(7): e103008.
13. Wang CL, Lu CY, Hsueh YC, Liu WH, Chen CJ*. Activation of antitumor immune responses by Ganoderma formosanum polysaccharides in tumor-bearing mice. Appl Microbiol Biotechnol. 2014; 98(22): 9389-98.
14. Chung CH, Yeh SC, Chen CJ*, Lee KT*. Coenzyme Q0 from Antrodia cinnamomea in submerged cultures induces reactive oxygen species-mediated apoptosis in A549 human lung cancer cells. Evid Based Complement Alternat Med. 2014; 2014: 246748.
15. Wang CL, Lu CY, Pi CC, Zhuang YJ, Chu CL, Liu WH, Chen CJ*. Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors. BMC Complement Altern Med. 2012; 12(1): 119.
16. Wang CL, Pi CC, Kuo CW, Zhuang YJ, Khoo KH, Liu WH, Chen CJ*. Polysaccharides purified from the submerged culture of Ganoderma formosanum stimulate macrophage activation and protect mice against Listeria monocytogenes infection. Biotechnol Lett. 2011; 33(11): 2271-8.
17. Kono H, Chen CJ, Ontiveros F, Rock KL*. Uric acid promotes an acute inflammatory response to sterile cell death in mice. J Clin Invest. 2010; 120(6): 1939-49.
18. Chen CJ, Kono H, Golenbock D, Reed G, Akira S, Rock KL*. Identification of a key pathway required for the sterile inflammatory response triggered by dying cells. Nat Med. 2007; 13(7): 851-6.
19. Chen CJ, Shi Y, Hearn A, Fitzgerald K, Golenbock D, Reed G, Akira S, Rock KL*. MyD88-dependent IL-1 receptor signaling is essential for gouty inflammation stimulated by monosodium urate crystals. J Clin Invest. 2006; 116(8): 2262-71.
20. Rock KL*, Hearn A, Chen CJ, Shi Y. Natural endogenous adjuvants. Springer Semin Immunopathol. 2005; 26(3): 231-46.
21. Chen CJ, Sugiyama K, Kubo H, Huang C, Makino S*. Murine coronavirus nonstructural protein p28 arrests cell cycle in G0/G1 phase. J Virol. 2004; 78(19): 10410-9.
22. Chen CJ, Makino S*. Murine coronavirus replication induces cell cycle arrest in G0/G1 phase. J Virol. 2004; 78(11): 5658-69.
23. Narayanan K, Chen CJ, Maeda J, Makino S*. Nucleocapsid-independent specific viral RNA packaging via viral envelope protein and viral RNA signal. J Virol. 2003; 77(5): 2922-7.
24. Chen CJ, Makino S*. Murine coronavirus-induced apoptosis in 17Cl-1 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and bid cleavage. Virology. 2002; 302(2): 321-32.
25. Chen CJ, An S, Makino S*. Induction of apoptosis in murine coronavirus-infected 17Cl-1 cells. Adv Exp Med Biol. 2001; 494: 615-20.
26. An S^†, Chen CJ^†, Yu X, Leibowitz JL, Makino S*. Induction of apoptosis in murine coronavirus-infected cultured cells and demonstration of E protein as an apoptosis inducer. J Virol. 1999; 73(9): 7853-9.  (^†equal contribution)
27. Huang JH*, Chen CJ, and Su YC. Production of chitinolytic enzymes from a novel species of Aeromonas. J Ind Microbiol. 1996; 17: 89-95.