2012.5.18 韩家淮教授(厦门大学)学术报告

时间:2012年05月14日 访问次数:1013

报告题目:Public T Cell Response and Beyond

报告人:   韩家淮 博士

                 厦门大学生命科学学院教授、长江学者特聘教授

                 医学与生命科学学部(医学部)主任

                 细胞应激生物学国家重点实验室主任
主持人:  冯新华  教授

时   间:  2012年5月18日(星期五)下午4点

地   点:  医学院综合楼307室


报告人介绍: 

        韩家淮教授在世界上率先发现p38信号通路。细胞内存在多条信号通路以介导不同的生物学反应。p38信号通路是细胞内最重要的信号通路之一,它在许多生物学反应包括细胞周期调控、细胞增殖、发育、分化、衰老、凋亡、免疫反应及肿瘤发生中起重要作用。韩家淮教授领导的实验室在p38信号通路的研究领域一直保持世界领先地位。韩家淮教授的研究重点是在先天性免疫系统中细胞内信号的传导。研究方向包括:1.炎症反应及免疫性疾病的分子机制;2.应激(如辐射、许多化学致癌物、病原体感染、炎症因子与基因突变等)反应与癌症发生以及其它疾病的关系。 
迄今已在世界主流学术刊物上发表论文200余篇,其中9篇发表在Cell,Nature,Science上(6篇为通讯作者),14篇发表在Cell和Nature的姊妹杂志上(8篇为通讯作者),并获美国专利多项。截止至2012年1月,论文被他人引用20000余次,单篇最高引用率2000余次。韩家淮教授的研究成果将会有助于进一步了解传染及免疫性疾病、心血管疾病和癌症发生的分子机理,从而为预防治疗这些人类顽疾提供一些新的思路和方法。

       所获荣誉介绍:比利时Jean Stas奖 (1991),美国心脏协会成熟研究员奖 (1995),中国国家自然科学基金杰出青年奖(B类) (2001),“卢嘉锡优秀导师奖” (2009),“药明康德生命化学研究奖”一等奖 (2009),“长江学者成就奖” (2009),自然科学研究一等奖 (2011)。

Abstract:

Overlap of T-cell receptor (TCR) repertoires among individuals provides the molecular basis for public T-cell responses. By deep-sequencing the TCRβ repertoires of CD4+CD8+ (DP) thymocytes from three individual mice, we observed that a substantial degree of TCRβ overlap (~10-15% of all unique amino acid sequences and ~5%-10% of all unique nucleotide sequences across any two individuals) is already present in DP thymocytes. Supporting the results obtained from peripheral T cells, our statistical correlation studies demonstrated that convergent recombination is a driving force in the inter-individual sharing of TCRβ sequences in DP thymocytes. By comparing the overlaps of the simulated repertoires and the overlaps of the empirical repertoires, we showed that a large part of the inter-individual overlap of TCRβ sequences could be attributed to convergent recombination, and as expected convergent recombination contributes less to the overlap in nucleotide sequences than to the overlap in amino acid sequences. However, given the unevenness of expression of different Vβ and Jβgenes, sharing also differed between different Vβ-Jβ combinations, and may also be affected by locus-specific biases in nucleotide deletion and addition. These biases were present in both thymic and peripheral repertoires, suggesting an important role of recombinatorial biases in determining the degree of TCR sharing while the role of selection during intra-thymic development was negligible. Our data provided new insight for the mechanisms that lead to overlap of TCRβ repertoires among individuals, and confirmed that the nature of TCR gene recombination, not selection, determines clonotype sharing among individuals.

Publications:

1.    Zhang DW, Shao J, Lin J, Zhang N, Lu BJ, Lin SC, Dong MQ, Han J. RIP3, an energy metabolism regulator that switches TNF-induced cell death from apoptosis to necrosis. Science, 325 (5938):332-336, 2009.

 2.    Sun P, Yoshizuka N, New L, Moser BA, Li Y, Liao R, Xie C, Chen J, Deng Q, Yamout M, Dong MQ, Frangou CG, Yates JR, 3rd, Wright PE, Han J. PRAK is essential for ras-induced senescence and tumor suppression. Cell, 128 (2):295-308, 2007.

 3.    Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J, Di Padova F, Lin SC, Gram H, Han J. Involvement of microRNA in AU-rich element-mediated mRNA instability. Cell, 120 (5):623-634, 2005.

 4.    Ge B, Gram H, Di Padova F, Huang B, New L, Ulevitch RJ, Luo Y, Han J. MAPKK-independent activation of p38alpha mediated by TAB1-dependent autophosphorylation of p38alpha. Science, 295 (5558):1291-1294, 2002.

 5.    Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ. Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature, 386 (6622):296-299, 1997.

 6.    Han J, Lee JD, Bibbs L, Ulevitch RJ. A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science, 265 (5173):808-811, 1994.