江伯倫 教授

學歷:

台大醫學院醫學士

美國加州大學戴維斯分校博士

 

研究興趣及方向

 

一.過敏性疾病的機轉研究和治療研發:

1) 我們研究室在過敏疾病的機轉和研發上一直都有著相當不錯的研究成果,其中包括過去幾年來在異位性皮膚炎的研究也發現金黃色葡萄球菌的腸毒素在異位性皮膚炎的致病機轉扮演著重要的角色。同時,這些腸毒素對第一型和第二型輔助細胞的細胞凋亡誘發的能力又有不同,這項發現可能解釋為何在異位性皮膚炎的小朋友在皮膚的表現會愈來愈嚴重的原因。此篇論文也已經為【免疫學雜誌(Journal of Immunology)】所接受發表,顯示其重要性。同時,一篇研究導致過敏免疫反應的基因及分子研究,我們發現一個與免疫反應有關的分子,decoy receptor 3 (DcR3)在過敏的患者也較高,此一研究結果也已經發表在2004年的Journal of Allergy and Clinical Immunology2007年的Allergy期刊。而最近的研究目標則是著重於想改善異位性皮膚炎患童的睡眠,以進一步改善小朋友的睡覺,而可以減少在睡覺時不自主的抓癢而導致抓傷,讓異位性皮膚炎的症狀惡化。此外,研究室在未來幾年也將針對神經傳導物質與免疫發炎物質在過敏疾病中所扮演的角色作更深入的研究。

 

2) 過敏疾病的基因療法:由於基因體醫學的進步,我們努力於研發過敏疾病相關的分子和細胞療法。由於過敏疾病是由第二型T輔助細胞所主導的免疫發炎反應,所以我們便計畫將一些能夠調控第二型 T輔助細胞的細胞激素基因應用到這方面的治療。首先我們先為了將介白質-12(IL-12)的基因應用在DNA疫苗上,我們更以分子生物學的方法合成能夠表現介白質-12的載體。這些研究成果於1998年便發表於【人類基因療法(Human Gene Therapy)】期刊。2001年,我們更利用IL-12基因的質體直接由氣管給予,結果發現可以有效地抑制肺部的嗜伊紅性白血球浸潤,並能夠有效地降低過敏疾病動物模式的發炎反應,這些成果再度發表於【人類基因療法】,是目前國際上有關基因療法最好的一本期刊之一,顯示我們這些研究成果已經受到國際的重視。接續的研究結果也發現其他的細胞激素基因如介白質-10和轉形生長因子的基因療法,在過敏性氣喘的治療上也得到相當好的效果,也投稿到基因醫學雜誌(Journal of Genes Medicine)。另外,我們也利用IL-1ra的基因來治療氣喘,也發現有相當好的治療效果,此一研究成果發表在2006年的Gene Therapy期刊。

除了將這些細胞激素基因應用在過敏疾病的治療上,我們研究利用樹突細胞為主的細胞療法應用在過敏疾病治療上。我們最近的研究成果,利用經過CpG motifribavirin處理過的樹突細胞再注射入小鼠體內,也可以抑制呼吸道的發炎反應。由這些結果,也經接受發表於呼吸學排名第一的American Journal of respiratory and Critical Care Medicine。而接下來的結果我們也陸續發表於過敏疾病排名第一的Journal of Allergy and Clinical Immunology及基因療法的著名期刊Gene Therapy。同時,我們也利用會誘發細胞凋亡的基因FasL,合併樹突細胞的治療,應用到氣喘的治療上,此一研究成果發表在J Mol Med。這幾年來,siRNA的技術應用在各種疾病治療上也受到大家的重視。我們研究分別研究GATA-3IL-5IL-4IL-13eotaxin等基因的siRNA序列,並且應用到過敏疾病的治療上。目前有關這方面的研究成果已經有四篇論文分別發表在Mol TherapyGene TherapyJ Mol MedJ Gene Med,這方面的研究成果可以說是具有重要的地位。也因為在這分面的研究成果,我們也接受Current Gene Therapy的邀請,目前已經有兩篇綜論性文章發表;而也分別有論文發表在Current Medicinal ChemistryCurrent Opinion in Molecular Therapeutics

此外,我們也建立了方法來篩選可以應用到氣喘治療的藥物。主要是利用樹突細胞來作為篩選藥物的平台。我們在建立此一平台的過程中,也分別發表了兩篇論文分別於J Leuko BiolMol Pharmacol等兩篇期刊。而目前有五種不同所篩選到的化合物,正在完成最後的研究而申請專利中。

 

二.我們研究室在過去幾年間於自體免疫疾病有著相當多的研究其中包括全身性紅斑狼瘡和過敏性紫斑:

1) 有關全身性紅斑狼瘡的研究方面,敝研究室在過去幾年間一直從事全身性紅斑狼瘡的致病機轉和治療的研發。我們最近的研究結果發現在誘發全身性紅斑狼瘡的自體抗原中,凋亡的細胞和核小體扮演著重要的角色。我們利用樹突細胞當成抗原呈現細胞,已經找出重要的抗原,並達到治療的目的,此一研究成果也已經發表在風溼病學排名第一的期刊”Arthritis & Rheumatism”Rheumatology的期刊。目前更進一步研究凋亡細胞的角色和找出其他的治療方法。

2) 同時,我們在風溼病的研究上,也包括過敏性紫斑(anaphylactoid purpura)。我們在過去幾年來,一直從事於其致病機轉的研究,有著相當好的研究成果。同時,這些研究成果也為風溼病學的教科書(Rheumatology, Mosby Publishing 2002, p1678)和孩童風溼病學(Pediatric Rheumatology)所引用,作者在文內一直強調這是非常有興趣的研究結果,對過敏性紫斑的致病機轉有著重要的突破。更重要的是,我們最近的研究已經將過敏性紫斑的自體抗原找出,這在兒童風溼病的研究上將是一個非常重要的突破發現。

 

三.病毒的研究:

1) 腸病毒:我們在過去幾年分別建立腸病毒的DNA疫苗和腸病毒VP-1基因轉殖番茄,分別來誘發抗腸病毒的免疫反應,達到避免感染的目的。而我們目前與國立清華大學及生物技術開發中心進行腸病毒的疫苗研發,目前也已經進入到在猴子體內注射而誘發有效的抗體,希望可以在未來幾年真正進入到臨床上。

2) B型肝炎病毒:我們最近的研究針對B型肝炎病毒的免疫研究,主要是著重在B型肝炎與自然免疫細胞和免疫反應之間的關係。

 

論文著作(五年內)

 

2004              Chen, C.-C., Yang, Y.-H., Lin, Y.-T., Hsieh, S.-L. and Chiang, B.-L. Increased soluble decoy receptor 3 level in atopic patients. J Allergy Clin Immunol 114:195-197.*

2004              Yang, Y.-H., Lai, H.-J., Kao, C.-K., Lin, Y.-T. and Chiang, B.-L. Transforming growth factor-b (TGF-b) gene promoter C-509T and tumor necrosis factor-a (TNF-a) gene promoter G-308A polymorphisms in Chinese children with Henoch-Scholein Purpura. Pediatr Nephrol 19:972-975.*

2004              Chen, Y.-S., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Risk of infection in children with systemic lupus erythematosus: A ten years follow-up. Clin Rheumatol 23: 235-238.*

2004              Hsu, C.-T., Lin, Y.-T., Yang, Y.-H. and Chiang, B.-L. Factors affecting the clinical and therapeutic outcomes of patients with juvenile rheumatoid arthritis. Scand J Rheumatol 33:312-317.*

2004              Ye, Y. -L., Lee, Y. -L., Chuang, Z. -J., Lai, H. -J., Chen, C. -C., Tao, M. -H. and Chiang, B. -L. Cytokine expressing adenoviruses modulated dendritic cells alleviate airway inflammation in allergen-sensitized mice. J Allergy Clin Immunol 114:88-96*

2004              Wang, L.-C., Yang, Y.-H., Lu, M.-Y. and Chiang, B.-L. Retrospective analysis of the renal outcome of pediatric lupus nephritis. Clin Rheumatol 23: 318-323.*

2004              Chang, W.-L., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Gastrointestinal manisfestations in Henoch-Scholein purpura: A review of 261 patients. Acta Paediatr 93: 1427-1431.*

2004                Hsu, P.-Y., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Serum eosinophil cationic protein level correlates with disease activity in childhood rhnitis. Asian Pacific J Allergy Immunol  22:19-24.*

2004              Wang, L.-J., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Immunological and clinical features in pediatric patients with primary hypogammaglobulinemia in Taiwan. Asian Pacific J Allergy Immunol 22:25-31.*

2004              Yang, Y.-H., Lai, H.-J., Huang, C.-M., Wang, L.-C., Lin, Y.-T. and Chiang, B.-L. Sera from children with active Henoch-Scholein purpura can enhance the production of interleukin-8 by human umbilical venous endothelial cells. Ann Rheum Dis 63:1511-1513.*

2004              Suen, J.-L., Chuang, Y.-H., Tsai, Y.-C., Yau, P.M. and Chiang, B.-L. Treatment of murine lupus using nucleosomal T cells epitopes identified by bone  marrow-derived dendritic cells. Arthritis Rheum 50:3250-3259.*

2004              Wang, I.-J., Chen, C.-L., Yang, Y.-H., Lin, Y.-T., Tsai, Y.-H., Chiang, B.-L. and Hwang, K.-C. The correlation of age and allergens in atopic dermatitis. Ann Allergy Asthma & Immunol  93:334-338.*

2004              Chuang, Y.-H., Fu., C.-L., Lo, Y.-C. and Chiang, B.-L. Adenovirus-expressing Fas ligand decreases airway hyperresponsiveness in a murine model of asthma. Gene Therapy 11:1497-1505.*

2005              Yang, M.-H., Suen, J.-L., Li, S.-L. and Chiang, B.-L. Identification of T-cell epitopes on U1A protein in MRL/lpr mice: Double negative T cells are the major responsive cells. Immunology 115:279-286.*

2005              Lin, Y.-L., Liang, Y.-C., Lee, S.-S. and Chiang, B.-L. Polysaccharide purified from Ganoderma lucidum induced activation and maturation of human monocyte-derived dendritic cells by the NF-kB and p38 mitogen-activated protein kinase pathways. J Leuko Biol 78:533-543.*

2005              Yang, Y.-H., Horng, C.-F., Hsu, C.-R., Wang, L.-C., Chuang, Y.-H., Lin, Y.-T. and Chiang, B.-L. The epidemiological characterisitics of childhood Henoch-Scholein purpura in Taiwan. Rheumatology 44:618-622.*

2005              Chang, W.-L., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Renal manisfestations in Henoch-Scholein purpura: A 10-year epidemiological and clinical study. Pediatr Nephrol 20: 1269-1272.*

2005              Liang, T.-C., Yang, Y.-H., Lin, Y.-T. and Chiang, B.-L. Analysis of childhood reactive arthritis and comparison with juvenile rheumatoid arthritis. Clin Rheumatol 24: 388-393.*

2005              Lee, C-C., Yang, Y.-H. and Chiang, B.-L. Calcinosis universalis complicating juvenile dermatomyositis. Arthritis & Rheum 52:1626.*

2005              Yang, Y.-H., Huang, Y.-H., Peng, C.-M., Chuang, Y.-H., Wang, L.-C., Lin, Y.-T., Chiang, B.-L. Autoantibodies against human epithelial cells and endothelial cells after severe acute respiratory syndrome (SARS)-associated coronary infection. J. Med Virol 77:1-7.*

2005              Lee. J.-H., Lin. Y.-T., Yang, Y.-H. and Chiang, B.-L. Increased Levels of Serum Specific immunoglobulin E to staphylococcal enterotoxin A and B in patients with allergic rhinitis and bronchial asthma. Int Arch Allergy Immunol 138:305-311.*

2006              Lee, J.-H., Wang, L.-C., Lin, Y.-T., Yang, Y.-H., Lin, D.-T. and Chiang, B.-L.  Inverse correlation between CD4+ regulatory T cells and autoantibody level in pediatric patients with systemic lupus erythematosus. Immunology 117: 280-286.*

2006              Wu, K.-H., Ho, M.-Y., Wu, W.-M., Lu, M.-Y. and Chiang, B.-L. Inhibitory effct of pooled human immunoglobulin on cytokine production of peripheral blood mononuclear cells. Ped Allergy Immunol 17: 60-68.*

2006              Chen H.-F., Chang, M.-F., Chiang, B.-L.and Jeng, S.-T. Immune responses of mice fed with tomato-derived VP1 from Enterovirus 71. Vaccine 24:2944-2951.*

2006              Chuang, Y.-H., Suen, J.-L. and Chiang, B.-L. Dendritic cell expressing Fas ligand decreases antigen-specific T cells and airway inflammation in murine model of asthma. J Mol Med 84:595-603.*

2006              Wang, C.-C., Fu, C.-L.,Yang, Y.-H., Lo, Y.-C., Chuang, Y.-H., Chang, D.-M. and Chiang, B.-L. Adenovirus-expressing interleukin-1 receptor antagonist alleviates airway inflammationa and eosinophilia in a murine model of asthma. Gene Therapy 13:1414-1421.*

2006              Fu C.-L., Lee Y.-L., Ye Y.-L., Chiang B.-L. Application of cytokine genes for the treatement of airway inflammation in animal model of asthma. Respiratory Research 7:72.*

2006              Fu, C.-L. and Chiang, B.-L. Adenovirus-expressing IL-10 gene alleviates airway inflammation in animal model of asthma. J Gene Med 8: 1393-1399.*

2006              Tzeng, T.-C., Suen, J.-L. and Chiang, B.-L. Dendritic cells pulsed with apoptotic body activate self-reactive T cells of lupus mice. Rheumatology 45:1230-1237.*

2006              Jou, S.-T., Chien, Y.-H., Yang, Y.-H., Shyur, S.-D., Chou, C.-C. and Chiang, B.-L. Variation in the human phosphoinositide 3-kinase p110d gene in children with primary B-cell immunodeficiency of unknown etiology. Int J Immunogenetics 33:361-369.*

2006              Yang, Y.-H., Huang, Y.-H., Wang, L.-C., Chuang, Y.-H, Lin, Y.-T. and Chiang, B.-L. Circulating IgA from children with Henoch-Scholein purpura can enhance endothelial interleukin-8 production through MEK/ERK signaling pathway. Clin Exp Immunol 144:247-253.*

2006              Lin, Y.-L., Lee, S.-S., Hou, S.-M. and Chiang, B.-L. Polysaccharide Purified from Ganoderma Lucidum Induce Gene Expression Changes in Human Dendritic Cells and Promote Th1 Immune Response in BALB/c Mice. Mol Pharmacol 70:637-644.*

2006              Yu, H.-H., Lee, J.-H., Wang, L.-C., Yang, Y.-H., and Chiang, B.-L.. Neuro-psychiatric manifestations in pediatric systemic lupus erythematosus: A twenty-year study. Lupus 15: 651-657.*

2006              Wu, J.-F., Yang, Y.-H., Wang, L,-C., Lee, J.-H., Shen, E.-Y. and Chiang, B.-L. Anti-nucleosome antibodies correlated with disease severity in children with systemic lupus erythematosus, J Autoimmunity 27:119-124.*

2006              Hsu, W.-T., Suen, J.-L. and Chiang, B.-L. The role of CD4+ CD25+ T cells in the autoantibody production in murine lupus. Clin Exp Immunol 145: 513-519.*

2006              Hung, S.-H., Lin, Y.-T., Yang, Y.-H. and Chiang, B.-L.  Clinical predictors of self-limited urinalysis abnormality in childhood Henoch-Schonlein purpura nephritis. Acta Pdeadtirica 95:306-311.*

2007              Lee, J.-H., Yang, Y.-H., Lin, Y.-T., Wang, L.-C. and Chiang, B.-L. Characterization of CD4+ regulatory T cells in pediatric allergic patients. Clin Exp Immunol 148:53-63.*

2007              Wu, J.-F., Yang, Y.-H., Wang, L.-J., Lee, J.-H., Shen, E.-Y. and Chiang, B.-L. Comparative usefulness of C-reactive protein and erythrocyte sedimeadation rate in patients with juvenile rheumatoid arthritis. Clin Exp Rheumatol 25:782-785.*

2007              Lin, Y.-T., Wang, C.-T., Lee, J.-H., Chu, C.-Y., Tsao, W.-C., Yang, Y.-H. and Chiang, B.-L. Higher Bcl-2 levels decrease Staphylococcal superantigen (SsAg)-induced apoptosis of CD4+ T cells in atopic dermatitis patients. Allergy 62:520526.*

2007              Lin, Y.-T., Wang, C.-T. and Chiang, B.-L. Role of bacterial pathogens in atopic dermatitis. Clin Rev Allergy Immunol 33:167-177.*

2007              Chieh, Y.-H., Hwu, W.-L. and Chiang, B.-L. The genetics of atopic dermatitis. Clin Rev Allergy Immunol 33:178-190.*

2007              Wang, L.-C. and Chiang, B.-L. Novel biological approaches in asthma- DNA-based therpapy. Current Med Chem 14: 1607-1618.*

2007              Hung, S.-H., Lin, Y.-T., Chu, C.-Y., Lee, Yang, Y.-H., Wang, L.-C. and Chiang, B.-L. Comparison with the change of colonization of Staphylococcus aureus after topical use of glucocorticoid, tarcolimus or antibiotics. Ann Allergy and Immunol 98:51-56.*

2007              Yu, H.-H., Wang, L.-C., Lee, J.-H., Lee, C.-C., Yang, Y.-H. and Chiang, B.-L. Lymphopenia is associated with neuropsychiatric manifestations, disease activity, organ damage, and in pediatric systemic lupus erythematosus patients. Rheumatology 46:1492-1494*

2007              Lin, Y.-L., Liang, Y.-C. and Chiang, B.-L. Plancental growth factor downregulates type 1 T helper immune response by modulating the function of dendritic cells. J Leuko Biol 82: 1473-1480.*

2008              Chen, C.-H., Wang, L.-C., Lee, J.-H., Lin, Y.-T., Yang, Y.-H., Kao, C.-L. and Chiang, B.-L. Ribavirin treatment reduced allergen sensitization and asthma development in high risk young children with respiratory syncythial virus bronchiolitis. Pediatr Allergy Immunol 19:166-172.*

2008              Lee, C.-C., Huang, H.-Y. and Chiang, B.-L. Lentiviral mediated RNAi against GATA-3 decreases allergic airway inflammation and hyperresponsiveness. Molecular Therapy 16: 60-65.*

2008              Yen, C.-H., Dai, T.-S., Yang, Y.-H., Wang, L.-C., Lee, J.-H. and Chiang, B.-L. Lower linolic acid metabolism and higher transepidermal water loss in children with atopic dermatitis. Ann Allergy & Immunology 100:66-73.*

2008              Huang, H.-Y., lee, C.-C. and Chiang, B.-L. Specific inhibition of interleukin-5 by small interfering RNA(siRNA) to decrease the eosinophilia and airway inflammation in a murine model of asthma. Gene Therapy 15:660-667.*

2008              Chen, L.-Y., Lin, Y.-L. and Chiang, B.-L. Levamisole enhances immune response through the effect on activation and maturation of human monocyte-derived dendritic cells. Clin Exp Immunology 151: 174-181.*

2008              Yang, M.-C., Lee, J.-H., Yang, Y.-H. and Chiang, B.-L. Improvement of juvenile dermatomyositis with calcinosis universalis after treatment with intravenous immunoglobulin. APLAR J Rheumatol (In press)*

2008              Jan, R.-H., Wen, S.-H., Shyr, M.-H. and Chiang, B.-L. Impact of maternal and neonatal factors on the CD34+, the total nucleated cells and the volume of cord blood units. Pediatr Transplantation (In press)*

2008              Fu, C.-L., Chuang, Y.-H., Huang, H.-Y. and Chiang, B.-L. Induction of IL-10-producing CD4+ T cells with regulatory activitied by stimulation with IL-10 gene-modified bone marrow derived DCs. Clin Exp Immunol 153: 258-268.*

2008              Yang, Y.-H., Chuang, Y.-H., Wang, L-C., Huang, H.-Y., Gershwin, M.E. and Chiang, B.-L. Immunobiology of Henoch-Scholein purpura. Autoimmunity Rev 7: 179-184.*

2008              Lee, C.-C. and Chiang, B.-L. RNA interfenerce: New therapeutics for allergic diseases. Current Gene Therapy 8:236-246.*

2008              Hung, J.-T., Yang, Y.-H., Hsiao, C.-H., Yu, H.-H., Lee, J.-H., Wang, l.-C. and Chiang, B.-L. Severe cardiac involvement in an infant with leukocytoclastic vasculitis: A case report. Clin Rheumatol 27:945-947.*

2009              Wang, L.-C., Lin, Y.-L., Yang, Y.-H., Lee, J.-H., Yu, S.-H., Wu, W.-M. Chiang, B.-L. Caffeic acid phenethyl ester inhibits dendritic cells activation through NF-kappa B signaling pathway but does not Inhibit the antigen presentation ability of dendritic cells. BMC Immunology (In press)*

2009              Tsai, B.-Y., Suen, C.-L and Chiang, B.-L. Lentiviral mediated Foxp-3 RNAi suppresses tumor growth of regulatory T cell-like leukemia in a murine tumor model. Gene Therapy (Revised)*

2009              Chen, C.-H., Lin, Y.-T., Wen, C.-Y., L-C Wang, L.-C., Lin, K.-H.,  Chiu, S.-H.,Yang, Y.-H.  Lee, J.-H. and Chiang, B.-L. Quantitative assessment of allergic shiners in children with allergic rhinitis. J Allergy Clin Immunol 123:665-671.*

2009              Lee, J.-H., Chen, S.-Y., Chu, S.-W., Wang, L.-F., Sun, C.-K. and Chiang, B.-L. Noninvasive in vivo assessment of skin lesions in atopic dermatitis. J Biomed Optics 14:014008.*

2009              Chuang, Y.-H. and Chiang, B.-L. Gene therapy for allergic diseases. Curr Gene Therapy (In press)*

2009              Lin, Y.-L., Liang, Y.-C., Chou, S.-Y., Hseu, R.-S., Huang, C.-T. and Chiang, B.-L. An immunomodulatory protein, Ling Zhi-8. Induced activation and maturation of human monocyte-derived dendritic cells through NF-kB and MAPK pathway. J. Leuko Biol (In press)*

2009              Huang, H.-Y., Lee, C.-C. and Chiang, B.-L. Small interfering RNA against eotaxin decreases airway eosinophilia and hyperresponsiveness. J Gene Med 11:112-118.*

2009              Huang, M.-T., Chou, Y.-B., Liu, C.-Y., Shieh, F.-J., Chen, P.-J. and Chiang, B.-L. Regulatory T cells inhibits airway airway angiogenic remodeling via notch pathway. J Immunol (Revised)*

2009              Tsai, B.-Y., Lin, Y.-L. and Chiang, B.-L. Application of interleukin-12 expressing dendritic cells for the treatment of animal model of leukemia. Exp Biol Med (In press)*

2009              Yang, Y.-H., Chang, C.-J., Chuang, Y.-H., Hsu, H.-Y., Chen, P.P. and Chiang, B.-L. Identification of anti-prothrombin antibodies in the antiphospholipid syndrome that display the peothrombinase activity. Ann Rheum Dis (Revised)*

2009              Tsai, B.-Y., Lin, Y.-L., and Chiang, B.-L. Autoimmune response induced by dendritic cells exerts anti-tumor effect in  murine model of leukemia.  J Autoimmuniity (Revised)*