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2017年11月22日 星期三 农历壬辰年
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何贤辉研究员
 

何贤辉,博士,研究员,生物化学与分子生物学博士研究生导师,免疫学硕士研究生导师。广东省免疫学会理事,Acta Biochimica et Biophysica Sinica编委。1986年毕业于厦门大学生物系生物化学专业,获理学学士学位;1990年于中国科学院上海生物化学研究所,获理学硕士学位;1999年于香港中文大学医学院获博士学位;1999年进入暨南大学临床医学博士后流动站从事免疫学相关研究工作,2001年出站并升任副研究员,留校工作;2004年升任研究员。早年通过基因突变与定点PEG修饰相结合改造天花粉蛋白,获得保留生物活性而过敏原性降低的衍生物,发表的相关论文被多次引用。近年来对源自于中草药的天然药物的抗炎和抗肿瘤作用机制进行了较多研究,并探索表观药物与天然产物联用的抗肿瘤效应和机制。目前的研究方向为:炎症与炎症免疫药理、分子免疫、肿瘤药理,主要研究抗原特异性CD8+ T细胞的特性、功能和记忆细胞的形成及其与病毒性疾病的相关性,探索炎症反应与细胞自噬的相互关系,以及抗炎药物的作用机制,并从细胞和分子水平分析天然药物的抗肿瘤作用机制,为肿瘤、病毒感染和炎症相关疾病的临床研究和治疗等提供实验依据。曾先后主持或参与“973”项目课题、国家自然科学基金项目以及重大新药创制十二五专项课题等项目,先后在AutophagyMol Cell ProteomicsJ ProteomicsClin ImmunolJ Cell BiochemJ Clin ImmunolTissue AntigensInt Immunopharmacol等国际专业期刊以及《免疫学杂志》等国内期刊发表研究论文100多篇。

主要研究课题:

(1)    国家自然科学基金面上项目:聚乙二醇修饰对天花粉蛋白生物活性与免疫活性的影响(39570822),1996.1-1998.12   负责人。已结题。

(2)    国家自然科学基金面上项目:CD40-FasL融合蛋白阻断T细胞活化信号及诱导靶向凋亡的免疫药理研究(30371651)19万,2004.12006.12,负责人。已结题。

(3)    国家“973”项目子课题,个体化机体衰老评价系统的研究,(“衰老机理及老年疾病防治的基础研究之第六子课题) (G2000057006)60万,2000.4-2005.3,负责人。已结题。

(4)    国家自然科学基金面上项目:B7-H1/B7-DCPD-1新型受体基因的克隆及其功能研究(30572199),30万,2006.12008.12,负责人。已结题。

(5)    “973”项目子课题,抗体抗原复合物的分子分布特征及功能识别基础 (2010CB833603) 2010.1-2014.1225万,负责人。

(6)    人类重大疾病灵长类动物模型资源平台的建设(2011ZX09307-303-03重大新药创制十二五专项子课题,2011.1-2013.1245万,负责人。

(7)    国家自然科学基金面上项目:葫芦素B通过持续激活cofilin干扰肌动蛋白细胞骨架动力学的抗肿瘤机制研究(81173604), 2012.1.1-2015.12.31,58万,欧阳东云(负责人),何贤辉(第二)。

发表论文(*为通讯作者):

[1]    Zhang YT, Ouyang DY, Xu LH, Zha QB, He XH*. Formation of cofilin-actin rods following cucurbitacin-B-induced actin aggregation depends on slingshot homolog 1-mediated cofilin hyperactivation. J Cell Biochem. 2013 May 20. doi: 10.1002/jcb.24587. [Epub ahead of print]

[2]    Ouyang DY, Xu LH, He XH*, Zhang YT, Zeng LH, Cai JY, Ren S. Autophagy is differentially induced in prostate cancer LNCaP, DU145 and PC-3 cells via distinct splicing profiles of ATG5. Autophagy. 2013; 9(1):20-32.

[3]    Qiao J, Xu LH, He J, Ouyang DY, He XH*. Cucurbitacin E exhibits anti-inflammatory effect in RAW 264.7 cells via suppression of NF-κB nuclear translocation. Inflamm Res. 2013; 62(5):461-469.

[4]    He J, Wang Y, Xu LH, Qiao J, Ouyang DY, He XH*. Cucurbitacin IIa induces caspase-3-dependent apoptosis and enhances autophagy in lipopolysaccharide-stimulated RAW 264.7 macrophages. Int Immunopharmacol. 2013; 16(1):27-34.

[5]    Ren S, Ouyang DY, Saltis M, Xu LH, Zha QB, Cai JY, He XH*. Anti-proliferative effect of 23,24-dihydrocucurbitacin F on human prostate cancer cells through induction of actin aggregation and cofilin-actin rod formation. Cancer Chemother Pharmacol. 2012; 70(3):415-424.

[6]    Zhu JS, Ouyang DY, Shi ZJ, Xu LH, Zhang YT, He XH. Cucurbitacin B Induces Cell Cycle Arrest, Apoptosis and Autophagy Associated with G Actin Reduction and Persistent Activation of Cofilin in Jurkat Cells. Pharmacology. 2012; 89(5-6):348-356.

[7]    Shi ZJ, Ouyang DY, Zhu JS, Xu LH, He XH. Histone deacetylase inhibitor suberoylanilide hydroxamic acid exhibits anti-inflammatory activities through induction of mitochondrial damage and apoptosis in activated lymphocytes. Int Immunopharmacol. 2012; 12(4):580-587.

[8]    Zhang Y, Ouyang D, Xu L, Ji Y, Zha Q, Cai J, He X*. Cucurbitacin B induces rapid depletion of the G-actin pool through reactive oxygen species-dependent actin aggregation in melanoma cells. Acta Biochim Biophys Sin. 2011; 43(7): 556-567.

[9]    Ouyang D, Zhang Y, Xu L, Li J, Zha Q, He X*. Histone deacetylase inhibitor valproic acid sensitizes B16F10 melanoma cells to cucurbitacin B treatment. Acta Biochim Biophys Sin. 2011; 43(6): 487-495.

[10]Ouyang DY, Ji YH, Saltis M, Xu LH, Zhang YT, Zha QB, Cai JY, He XH*. Valproic acid synergistically enhances the cytotoxicity of gossypol in DU145 prostate cancer cells: An iTRAQ-based quantitative proteomic analysis. J Proteomics. 2011, 74(10): 2180-2193.

[11]He D, Yau K, He X, Shi H, Zheng Y, Tam S. Conversion of trichosanthin-induced CD95 (Fas) type I into type II apoptotic signaling during Herpes simplex virus infection. Mol Immunol. 2011; 48(15-16):2000-2008.

[12]Chen Q, Ouyang DY, Geng M, Xu LH, Zhang YT, Wang FP, He XH. Valproic acid exhibits biphasic effects on apoptotic cell death of activated lymphocytes through differential modulation of multiple signaling pathways. J Immunotoxicol. 2011; 8(3):210-218.

[13]Ouyang D, He X*, Xu L, Wang X, Gao Q, Guo H. Differential cell surface expression of rhesus macaque's major histocompatibility complex class I alleles Mamu-B*1703 and Mamu-B*0101. Acta Biochim Biophys Sin. 2010; 42(4):281-287.

[14]Ji YH, Ji JL, Sun FY, Zeng YY, He XH, Zhao JX, Yu Y, Yu SH, Wu W. Quantitative proteomics analysis of chondrogenic differentiation of C3H10T1/2 mesenchymal stem cells by iTRAQ labeling coupled with on-line two-dimensional LC/MS/MS. Mol Cell Proteomics. 2010; 9(3):550-564.

[15]Ouyang D, Wang X, He X*, Xu L, Shi H, Gao Q, Guo H. Construction of soluble Mamu-b*1703, a class I major histocompatibility complex of Chinese rhesus macaques, monomer and tetramer loaded with a simian immunodeficiency virus peptide. Cell Mol Immunol. 2009; 6(2):117-122.

[16]Ouyang DY, Xu LH, Shi HJ, Zheng YT, He XH*. Eight novel MHC class I alleles identified in Chinese-origin rhesus macaques. Tissue Antigens. 2009; 73(3):285-287.

[17]Wu Y, Lu H, Cai J, He X, Hu Y, Zhao H, Wang X. Membrane Surface Nanostructures and Adhesion Property of T Lymphocytes Exploited by AFM. Nanoscale Res Lett. 2009; 4(8):942-7.

[18]Ouyang D, Xu L, Dai Z, Shi H, Zhang G, Zheng Y, He XH*. Identification of major histocompatibility complex class I alleles in Chinese rhesus macaques. Acta Biochim Biophys Sin. 2008; 40(11):919-927.

[19]He XH* Jia QT, Li FY, Saltis M, Liu Y, Xu LH, Zha QB. CD8+ T cells specific for both persistent and non-persistent viruses display distinct differentiation phenotypes but have similar level of PD-1 expression in healthy Chinese individuals. Clin Immunol. 2008; 126(2): 222-234.

[20]He XH*, Zha QB, Liu Y, Xu LH, Chi XY. High frequencies cytomegalovirus pp65495-503- specific CD8+ T cells in healthy young and elderly Chinese donors: characterization of their phenotypes and TCR Vb usage. J Clin Immunol, 2006, 26(5): 417-429.

[21]He XH*, Xu LH, Liu Y. Enhancement of binding activity of soluble human CD40 to CD40 ligand through incorporation of an isoleucine zipper motif. Acta Pharmacol Sin, 2006, 27(3): 333-338.

[22]Jia Q, Xu L, Zha Q, Chi X, Li F, He X*. High level expression of HLA-A*0203-BSP fusion protein in Escherichia coli and construction of soluble HLA-A*0203 monomer and tetramer loaded with Epstein-Barr virus peptide. Cell Mol Immunol. 2007; 4(4):301-308.

[23]Li F, Xu L, Zha Q, Chi X, Jia Q, He X*. Preparation and identification of HLA-A*1101 tetramer loading with human cytomegalovirus pp65 antigen peptide. Cell Mol Immunol. 2007; 4(2):141-146.

[24]Yue GP, Du LR, Xia T, He XH, Qiu H, Xu LH, Chen XD, Feng SQ, Yang ZQ. One in vitro model for visceral adipose-derived fibroblasts in chronic inflammation. Biochem Biophys Res Commun. 2005; 333(3):850-857.

[25]He XH*, Xu LH, Liu Y. Identification of a novel splice variant of human PD-L1 (B7-H1) mRNA encoding an isoform lacking IgV-like domain. Acta Pharmacol Sin, 2005, 26(4): 462-468.

[26]He XH*,Xu Lihui, Liu Yi, Zeng Yaoying. Identification of a novel HLA-F allele-HLA-F*010102. Tissue Antigens. 2004; 63(2):181-183.

[27]He XH*, Liu Yi, Xu Li-Hui, Zeng Yao-Ying. Cloning and Identification of Two Novel Splice Variants of Human PD-L2. Acta Bioch Biophys Sin. 2004; 36(4): 284-289.

[28]He XH*Pang-Chui Shaw, Lihui Xu, and Siu-Cheung Tam, Reducing the immunogenicity and improving the in vivo activity of trichosanthin by site-directed pegylation. Life Sciences. 1999; 65(4): 355-368.

[29]He XH*Pang-Chui Shaw and Siu-Cheung Tam, Site-directed polyethylene glycol modification of trichosanthin: effects on its biological activities, pharmacokinetics, and antigenicity. Life Sciences. 1999; 64(14): 1163-1175.

[30]Wah-Lun Chan, Pang-Chui Shaw, Xiao-Bing Li, Qiong-Fang Xu, Xian-Hui He, and Siu-Cheung Tam, Lowering of trichosanthin immunogenicity by site-specific coupling to dextran. Biochem Pharmacol. 1999; 57(8): 927-934.

[31]Nie Huiling, Cai Xinfa, He Xianhui, Xu Lihui, Ke Xingyong, Ke Yibao, and Tam Siu-Cheung. Position 120-123, a potential active site of trichosanthin. Life Sciences. 1998; 62(6): 491-500.

[32]Ke Yi-Bao, Chen Jen-Kan, Nie Hui-Ling, He Xian-Hui, Ke Xin-Yong, and Wang Ya-Hui. Structure-function relationship of trichosanthin. Life Sciences. 1997; 60(7): 465-472.

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