DSC09565 複製

 

聯絡方式

  • 辦公室: 第一教學大樓N1023室
  • 實驗室: 第一教學大樓N1020室
  • 電話: (07) 3121101 ext. 2676
  • 傳真: (07) 3125339
  • 電子郵件: bhchen@kmu.edu.tw
  • 其他個人網頁:


學經歷

  • 中山醫學大學 醫事技術學系 學士 (1990)
  • 美國 維吉尼亞聯邦州立大學 臨床實驗科學研究所 碩士 (1995)
  • 美國 維吉尼亞聯邦州立大學 微生物與免疫學研究所 博士 (2001)
  • 美國 維吉尼亞聯邦州立大學 微生物與免疫學研究所 博士後研究 (2001-2002)
  • 國立清華大學 生命科學院 博士後研究 (2002-2003)
  • 高雄醫學大學 蛋白質體中心 學術合作組 組長 (2004-2006)
  • 高雄醫學大學 生物科技學系 系主任(2012/08 - 2015/07)


主負責授課科目

  • 生物科技導論
  • 生物科技實驗
  • 微生物學
  • 免疫學
  • 書報討論
  • 專題研究

研究興趣

  • 過敏與非過敏性發炎反應的分子生物學與細胞學的調控機制
  • 抗過敏與抗發炎藥物之篩選與開發
  • 肥大細胞與巨噬細胞之訊息傳遞機制研究
  • 細胞脫顆粒作用調控

 

Mechanistic Regulation of Allergic Inflammatory Responses in Mast Cells

由於工業化以及飲食西化的影響,第一型即發型過敏性疾病的罹患率有逐年增加的趨勢。此類過敏反應的成因,主要是由過敏原(: 花粉、塵蟎、花生、甲殼類海鮮、寵物皮屑等)所誘發B淋巴球製造的免疫球蛋白E (IgE),結合與促進肥大細胞或嗜鹼性球活化所造成的免疫疾病。研究發現,經由活化Th2 淋巴細胞或是其他發炎細胞(: 巨噬細胞)所分泌的細胞激素亦能直接或間接地造成過敏反應症狀的惡化。目前臨床上常用的治療過敏方法,包括給予病患症狀舒緩藥劑(: 抗組織胺)、類固醇、以及新開發的抗IgE 單株抗體,然而這些療法都各有其侷限或不足之處。因此,本實驗室之主要研究方向為了解肥大細胞的活化機制,期望可以探索與開發具有抑制過敏性發炎的新型製劑。

        

 

 

實驗室研究方向

  • 調控過敏與發炎性免疫反應的分子生物學與細胞學機制
  • 抗過敏與抗發炎藥物之篩選與開發
  • 白血球訊息傳遞機制研究
  • 設計與開發具醫療潛力的融合蛋白質

 

Mechanistic Regulation of Allergic Inflammatory Responses in Mast Cells

由於工業化以及飲食西化的影響,第一型即發型過敏性疾病的罹患率有逐年增加的趨勢。此類過敏反應的成因,主要是由過敏原(如: 花粉、塵蟎、花生、甲殼類海鮮、寵物皮屑等)所誘發B淋巴球製造的免疫球蛋白E (IgE),結合與促進肥大細胞或嗜鹼性球活化所造成的免疫疾病。研究發現,經由活化Th2 淋巴細胞或是其他發炎細胞(如: 巨噬細胞)所分泌的細胞激素亦能直接或間接地造成過敏反應症狀的惡化。目前臨床上常用的治療過
敏方法,包括給予病患症狀舒緩藥劑(如: 抗組織胺)、類固醇、以及新開發的抗IgE 單株抗體,然而這些療法都各有其侷限或不足之處。因此,本實驗室之主要研究方向為了解肥大細胞的活化機制,期望可以探索與開發具有抑制過敏性發炎的新型製劑。

allergy overview mast cell activation

 

 

  • 篩選新的抗過敏成份:

近年來,從天然食用與藥用植物中開發新的抗過敏成分已IMG_20160428_161214經逐漸受到重視。我們利用囓齒類RBL-2H3與人類KU812肥大細胞株為篩選平台,分析不同的植物萃取物是否可以抑制這些細胞株因過敏原/IgE刺激所造成的活化現象 (如: 去顆粒化作用、胞內鈣離子變化、細胞激素基因表現等),以用來當做評估其抗過敏潛力的指標。

  • 研究肥大細胞去顆粒作用的分子調控機制:

肥大細胞受到過敏原與IgE的刺激後,會將細胞質內的分泌型顆粒(secretory granules, SGs)經由胞吐作用(exocytosis),將其中的各類型致敏性媒介物(例如: TNFalpha, MCP-1, IL-4)排放到胞外,因而導致過敏症狀的發生。肥大細胞的胞吐作用又稱為去顆粒作用(degranulation)。目前研究顯示,影響去顆粒作用的關鍵因子,包括了胞內鈣離子濃度以及分泌型顆粒能否與細胞膜進行融合。此融合過程中,需要SGs與細胞膜上的不同蛋白質分子共同組成SNARE複合體(如: VAMP, SNAP, syntaxin);此外,SGs上的鈣離子偵測蛋白(如: synaptotagmin)在促進融合的過程也扮演著重要的調控角色。目前,我們有興趣研究人類與小鼠的肥大細胞株在去顆粒過程中,SNARE複合物的形成與調控上的差異、參與肥大細胞去顆粒作用的SNARE複合物形成之分子調控機制。

 

IMG_20160428_161732

IMG_20160428_211746

IMG_20160505_103432

IMG_20160505_103432_1

 

期刊論文 [近期發表論文(隨時更新)Google 學術搜尋]

  • Production of a chimeric form of CD23 that is oligomeric and blocks IgE binding to the Fc epsilonRI. Kelly AE, Chen BH, Woodward EC, Conrad DH. J. Immunol. 1998; 161:6696-6704. (PMID: 9862699)
  • Necessity of the stalk region for immunoglobulin E interaction with CD23. Chen BH, Ma C, Caven TH, Chan-Li Y, Beavil A, Beavil R, Gould H, Conrad DH. Immunology 2002; 107:373-381. (PMID: 12423314)
  • Temperature effect on IgE binding to CD23 versus Fc epsilon RI. Chen BH, Kilmon MA, Ma C, Caven TH, Chan-Li Y, Shelburne AE, Tombes RM, Roush E, Conrad DH. J. Immunol. 2003; 170:1839-1845. (PMID: 12574349)
  • Properties of human and rabbit cytosolic serine hydroxymethyltransferase are changed by single nucleotide polymorphic mutations. Fu TF, Hunt S, Schirch V, Safo MK, and Chen BH. Arch. Biochem. Biophys. 2005; 442:92-101. (PMID: 16137637)
  • Cloning, expression, purification, and characterization of zebrafish cytosolic serine hydroxymethyltransferase. Chang WN, Tsai JN, Chen BH, Fu TF. Protein Expr. Purif. 2006; 46:212-220. (PMID: 16242955)
  • Characterization of chondroitin sulfate and its interpenetrating polymer network hydrogels for sustained-drug release. Wang SC, Chen BH, Wang LF, Chen JS. Int. J. Pharm. 2007; 329:103-109. (PMID: 16996709)
  • Serine hydroxymethyltransferase isoforms are differentially inhibited by leucovorin: characterization and comparison of recombinant zebrafish serine hydroxymethyltransferases. Chang WN, Tsai JN, Chen BH, Huang HS, Fu TF. Drug Metab. Dispos. 2007; 35(11):2127-2137. (PMID: 17664250)
  • Type I IFN induced IL1-Ra expression in hepatocytes is mediated by activating STAT6 through the formation of STAT2 : STAT6 heterodimer. Wan L, Lin CW, Lin YJ, Sheu JJ, Chen BH, Liao CC, Tsai Y, Lin WY, Lai CH, Tsai FJ. J. Cell Mol. Med. 2008; 12(3):876-888. (PMID: 18494930)
  • Characterization and comparative studies of zebrafish and human recombinant dihydrofolate reductases --- Inhibition by folic acid and polyphenols. Kao TT, Wang KC, Chang WN, Lin CY, Chen BH, Wu HL, Shi GY, Tsai JN, Fu TF. Drug Metab. Dispos. 2008; 36(3): 508-516. (PMID: 18056255)
  • Poly(ethylene imine)-g-chitosan using EX-810 as a spacer for nonviral gene delivery vectors. Lou YL, Peng YS, Chen BH, Wang LF, Leong KW. J. Biomed Mater Res A. 2009; 15;88(4):1058-68. (PMID: 18404706)
  • Synthesis of calcium phosphates and porous hydroxyapatite beads prepared by emulsion method. Chen BH, Chen KI, Ho ML, Chen HN, Wang CK. Materials Chemistry and Physics 2009; 113: 365-371.
  • Puerariae radix isoflavones and their metabolites inhibit growth and induce apoptosis in breast cancer cells. Lin YJ, Hou YC, Lin CH, Hsu YA, Sheu JJ, Lai CH, Chen BH, Lee Chao PD, Wan L, Tsai FJ. Biochem. Biophys. Res. Commun. 2009; 378(4):683-8. (PMID: 19013426)
  • Antiallergic potential on RBL-2H3 cells of some phenolic constituents of Zingiber officinale (Ginger).Chen BH, Wu PY, Chen KM, Fu TF, Wang HM, Chen CY. J. Nat. Prod. 2009; 72, 950-53. (PMID: 19271742)
  • Association of the Lumican gene functional 3' UTR polymorphism with high myopia. Lin HJ, Kung YJ, Lin YJ, Sheu JJ, Chen BH, Lan YC, Lai CH, Shu YA, Wan L, Tsai FJ. Invest. Ophthalmol. Vis. Sci. 2010; 51(1):96-102. (PMID: 19643966)
  • Grape seed extract inhibits the growth and pathogenicity of Staphylococcus aureus by interfering with dihydrofolate reductase activity and folate-mediated one-carbon metabolism. Kao TT, Tu HC, Chang WN, Chen BH, Shi YY, Chang TC, Fu TF. Int. J. Food Microbiol. 2010; 30, 141(1-2):17-27. (PMID: 20483185)
  • p38 MAPK and NF-kappaB pathways are involved in naphtho[1,2-b] furan-4,5-dioone induced anti-proliferation and apoptosis of human hepatoma cells. Chiu CC, Chen JY, Lin KL, Huang CJ, Lee JC, Chen BH, Chen WY, Lo YH, Chen YL, Tseng CH, Chen YL, Lin SY. Cancer Lett. 2010; 295(1):92-99. (PMID: 20350781)
  • Additive effects of C(2)-ceramide on paclitaxel-induced premature senescence of human lung cancer cells. Chen JY, Hwang CC, Chen WY, Lee JC, Fu TF, Fang K, Chu YC, Huang YL, Lin JC, Tsai WH, Chang HW, Chen BH*, Chiu CC*. Life Sci. 2010; 87(11-12):350-7.
  • Betel quid extract promotes oral cancer cell migration by activating a muscarinic M4 receptor-mediated signaling cascade involving SFKs and ERK1/2. Chiu CC*, Chen BH*, Hour TC, Chiang WF, Wu YJ, Chen CY, Chen HR, Chan PT, Liu SY, Chen JY. Biochem Biophys Res Commun. 2010; 399(1):60-5.
  • Versatile phosphoramidation reactions for nucleic acid conjugations with peptides, proteins, chromophores, and biotin derivatives. Wang TP, Chiou YJ, Chen Y, Wang EC, Hwang LC, Chen BH, Chen YH, Ko CH. Bioconjug Chem. 2010; 21(9):1642-55.
  • CD23 sheddase A Disintegrin And Metallo-proteinase 10 (ADAM10) is also required for CD23 sorting into B cell derived exosomes. Mathews J, Gibb D, Chen BH, Scherle P, Conrad DH. J. Biological Chem. 2010; 285(48):37531-41.
  • Zebrafish Sp1-like protein is structurally and functionally comparable to human Sp1. Lin CJ, Hsiao TH, Chung YS, Chang WN, Yeh TM, Chen BH, Tu TF. Protein Expr. Purif. 2011; 76(1):36-43.
  • A novel targeting modality for renal cell carcinoma: human osteocalcin promoter-mediated gene therapy synergistically induced by vitamin C and vitamin D3. Johnson NA*, Chen BH*, Sung SY, Liao CH, Liao CH, Hsiao WC, Chung WK, Hsieh CL. J. Gene Med. 2010; 12(11):892-903.
  • (-)-Anonaine induces DNA damage and inhibits growth and migration of human lung carcinoma H1299 cells. Chen BH, Chang HW, Huang HM, Chong IW, Chen JS, Chen CY, Wang HM. J. Agric. Food Chem. 2011; 59(6):2284-90.
  • A Novel Interaction Between Interferon-Inducible Protein p56 and Ribosomal Protein L15 in Gastric Cancer Cells. Hsu YA, Lin HJ, Sheu JJ, Shieh FK, Chen SY, Lai CH, Tsai FJ, Wan L*, Chen BH*. DNA Cell Biology 2011; 30(9):671-9.
  • Anti-allergic activity of grapeseed extract (GSE) on RBL-2H3 mast cells. Chen BH*, Hung MH, Chen YF, Chang HW, Yu ML, Wan L, Tsai FJ, Wang TP, Fu TF, Chiu CC*. Food Chem. 2012; 132(2), 968-74. (WOS:000300475800041)
  • Biological properties of acidic cosmetic water from seawater. Liao WT, Huang TS, Chiu CC, Pan JL, Liang SS, Chen BH, Chen SH, Liu PL, Wang HC, Wen ZH, Wang HM, Hsiao SW. Int J Mol Sci. 2012;13(5):5952-71.

  • Methotrexate-induced decrease in embryonic 5-methyl-tetrahydrofolate is irreversible with leucovorin supplementation. Kao TT, Lee GH, Fu CC, Chen BH, Chen LT, Fu TF. Zebrafish. 2013; 10(3):326-37.

  • Folate deficiency-induced oxidative stress contributes to neuropathy in young and aged zebrafish--implication in neural tube defects and Alzheimer's diseases. Kao TT, Chu CY, Lee GH, Hsiao TH, Cheng NW, Chang NS, Chen BH, Fu TF. Neurobiol Dis. 2014;71:234-44. PMID: 25131448

  • Knocking down 10-Formyltetrahydrofolate dehydrogenase increased oxidative stress and impeded zebrafish embryogenesis by obstructing morphogenetic movement. Chang WN, Lee GH, Kao TT, Lin CY, Hsiao TH, Tsai JN, Chen BH, Chen YH, Wu HR, Tsai HJ, Fu TF. Biochim Biophys Acta. 2014 Jul;1840(7):2340-50. PMID: 28445049

  • Ethanol-induced upregulation of 10-formyltetrahydrofolate dehydrogenase helps relieve ethanol-induced oxidative stress. Hsiao TH, Lin CJ, Chung YS, Lee GH, Kao TT, Chang WN, Chen BH, Hung JJ, Fu TF. Mol Cell Biol. 2014;34(3):498-509. PMID: 

  • BPIQ, a novel synthetic quinoline derivative, inhibits growth and induces mitochondrial apoptosis of lung cancer cells in vitro and in zebrafish xenograft model. Chiu CC, Chou HL, Chen BH, Chang KF, Tseng CH, Fong Y, Fu TF, Chang HW, Wu CY, Tsai EM, Lin SR, Chen YL. BMC Cancer. 2015; 15:962. PMID: 26672745

  • Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. Yen CY, Hou MF, Yang ZW, Tang JY, Li KT, Huang HW, Huang YH, Lee SY, Fu TF, Hsieh CY, Chen BH*, Chang HW*. BMC Complement Altern Med. 2015; 15:94. PMID: 25880412

  • Antiallergic Phorbol Ester from the Seeds of Aquilaria malaccensis. Korinek M, Wagh VD, Lo IW, Hsu YM, Hsu HY, Hwang TL, Wu YC, Cheng YB, Chen BH*, Chang FR*. Int J Mol Sci. 2016;17(3). PMID: 27007372

  • Inhibitory effect of trans-ferulic acid on proliferation and migration of human lung cancer cells accompanied with increased endogenous reactive oxygen species and β-catenin instability.
    Fong Y, Tang CC, Hu HT, Fang HY, Chen BH, Wu CY, Yuan SS, Wang HD, Chen YC, Teng YN, Chiu CC.
    Chin Med. 2016 Oct 1;11:45. PMID: 27733866

  • Anti-allergic potential of Typhonium blumei: Inhibition of degranulation via suppression of PI3K/PLCγ2 phosphorylation and calcium influx. Korinek M, Chen KM, Jiang YH, El-Shazly M, Stocker J, Chou CK, Hwang TL, Wu YC, Chen BH*, Chang FR*. Phytomedicine. 2016 Dec 15;23(14):1706-1715. doi: 10.1016/j.phymed.2016.10.011. PMID: 27912872

  • Grape Seed Extract Attenuates Hepatitis C Virus Replication and Virus-Induced Inflammation. Chen WC, Tseng CK, Chen BH, Lin CK, Lee JC. Front Pharmacol. 2016 Dec 21;7:490. doi: 10.3389/fphar.2016.00490. PMID: 28066241

  • Dual roles of extracellular signal-regulated kinase (ERK) in quinoline compound BPIQ-induced apoptosis and anti-migration of human non-small cell lung cancer cells. Fong Y, Wu CY, Chang KF, Chen BH, Chou WJ, Tseng CH, Chen YC, Wang HD, Chen YL, Chiu CC. Cancer Cell Int. 2017 Mar 7;17:37. doi: 10.1186/s12935-017-0403-0. PMID: 28286419

  • The Transgenic Zebrafish Display Fluorescence Reflecting the Expressional Dynamics of Dihydrofolate Reductase. Chang WN, Chi WY, Kao TT, Tsai JN, Liu W, Liang SS, Chiu CC, Chen BH*, Fu TF*. Zebrafish 2017 doi: 10.1089/zeb.2016.1381. PMID: 28350247

  • Inflammation Modulatory Phorbol Esters from the Seed of Aquilaria malaccensis. Wagh VD, Korinek M, Lo IW, Hsu YM, Chen SL, Hsu HY, Hwang TL, Wu YC, Chen BH*, Cheng YB*, Chang FR*. J. Nat. Prod. 2017 doi: 10.1021/acs.jnatprod.6b01096. [Epub ahead of print] PMID: 28445049
  • A 4-Phenoxyphenol Derivative Exerts Inhibitory Effects on Human Hepatocellular Carcinoma Cells through Regulating Autophagy and Apoptosis Accompanied by Downregulating α-Tubulin Expression. Chang WT, Liu W, Chiu YH, Chen BH, Chuang SC, Chen YC, Hsu YT, Liu MJ, Chiou SJ, Chou CK, Chiu CC. Molecules 22(5): 854, 2017. doi:10.3390/molecules22050854

 

研討會論文

  • Serum metalloprotease inhibitors can inhibit CD23 cleavage and IgE production by B lymphocytes. Chen BH, Kilmon MA, Conrad DH. The 25th Mid-Atlantic Immunobiology Conference, Philadelphia, PA, USA, 1997.

  • Chimeric CD23 that demonstrates IgE binding capacity comparable to membrane CD23. Chen BH, Kelly AE, Conrad DH. FASEB Experimental Biology 1999, Washington, DC, USA, 1999.

  • Searching for the Cure to Allergy: Construction and Analysis of Chimeric CD23 Trimers. Chen BH, Conrad DH. The 28th Mid-Atlantic Immunobiology Conference, State College, PA, USA, 2000.

  • Structural and Functional Analysis of Murine Chimeric CD23 Stalk Deletion Mutants in Mediating IgE-binding Activity. Chen BH, Conrad DH. FASEB Experimental Biology 2001, Orlando, FL, USA, 2001.

  • Temperature effect on IgE binding to CD23 vs FcepsilonRI. Ma C, Chen BH, Kilmon MA, Chan-Li Y, Conrad DH. FASEB Experimental Biology 2002, New Orleans, LO, USA, 2002.

  • Surface plasmon resonance analysis of the CD23-IgE interaction. Roush ED, Ma C, Chen BH, and Conrad DH. FASEB Experimental Biology 2002, New Orleans, LO, USA, 2002.

  • Therapeutic approaches targeting IgE and mIgE-expressing B cells. Chang TW, Chen HY, Huang JS, and Chen BH. The 17th World Allergy Congress, St. Petersburg, Russia, 2003.

  • Cloning, expression, purification and characterization of zebrafish 10-formyltetrahydrofolate dehydrogenase. Lin HC, Chang WN, Chen BH and Fu TF. The 22th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan, 2007.

  • Cloning and characterization of zebrafish serine hydroxymethyltransferases. Chang WN, Tsai JN, Chen BH and Fu TF. The 21th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan, 2007.

  • Studies on the Anti-folate Potential of Grape Seed Extract. Kao TT, Want KC, Chang TC, Wu JJ, Chen BH, Fu TF. The 23th Joint Annual Conference of Biomedical Sciences, Taipei, Taiwan, 2008.

  • 10-formyltetrahydrofolate dehydrogenase is required for normal development of circulation system and neuronal morphogenesis in zebrafish embryos.    Fu TF, Lin HC, Lin CY, Chang WN, Chen BH. The 11th Annual MipTec Conference, Basel, Switzerland, 2009.

  • The interplay of CD23 and ADAM10 and its role in IgE synthesis. Mathews J, Chen BH, Conrad DH. The 96th Annual Meeting of The American Association of Immunologists, Seattle, Washington, 2009.

 

 

專利

  • COMPOSITIONS AND METHODS OF ANTIALLERGIC PHORBOL ESTER AND PHORBOL DERIVATIVES AS THE MAIN ACTIVE INGREDIENTS FROM THE SEEDS OF AQUILARIA MALACCENSIS. (發明者: Fang-rong Chang, Bing-hung Chen, Hsue-yin Hsu, Chen Hsieh, Hui-ping Hsieh; 發佈日期: 2017/9/21; 專利局: US; 專利編號: 20170266250)

文章瀏覽點擊數
548022
Go to top