Ralf Jauch
博士 研究员
所属大学: 中国科学院广州生物医药与健康研究院
所属学院: 未知
邮箱:
ralf@gibh.ac.cn
个人主页:
http://www.gibh.cas.cn/sourcedb_gibh_cas/zw/zjrc/201309/t20130903_3923159.html
个人简介
工作经历
2018年5月至今 客座研究员 中国科学院广州生物医药与健康研究院
2013年4月至2018年4月 研究员,中国科学院广州生物医药与健康研究院
2008年4月至2013年3月 副研究员, 新加坡基因组研究所
2006年1月至2008年3月 博士后,新加坡基因组研究所
2003年至2005年 博士,德国马克斯?普朗克研究所
2000年6月至10月 罗氏诊断试剂,德国
教育经历
2003-2005
博士研究生,分子与结构生物学,德国马克斯普朗克研究所,受指导于Herbert Jackle博士和Markus Wahl博士
2001-2003
硕士研究生,分子生物学,硕士/博士项目,德国
2000-2001
访问学生,分子生物学,曼彻斯特大学,英国
1998-2000
本科,生物学,弗里德理西-席勒?耶拿大学,耶拿,德国
Ralf Jauch博士是一名结构生化学家,并在基因组学、干细胞生物学和计算生物学等领域具有较强背 景,在德国和英国的大学和科学院受过严格的专业训练,对转录因子协同作用及其调控干细胞分化的分子机制,做出过原创性发现。近年来取得很多突破性成果,以第一作者或重要作者身份发表科研论文超过30篇,其多篇重要文章先后发表在Nature Cell Biol、Stem Cell、Nucleic Acid Res、EMBO等 国际知名学术刊物;
在Jauch博士的学术成果中,以阐明多能干细胞的早期分化原理尤为突出,得到了学术界的广泛认同。他发现Sox转录因子家族中的两个不同成员(Sox2,Sox17)均能结合控制细胞重编程的关键转录因子(Oct4),并形成二聚体复合物,但这两种复合物的生物功能完全不同。Sox2/Oct4调控体细胞重编程的发生和效率;Sox17/Oct4复合物调控多能干细胞往内胚层方向的分化。Sox2和Sox17之间只需要突变一个氨基酸,就会导致诱导体细胞重编程或多能干细胞往内胚层分化的功能互换。这个突破性发现为干细胞的应用、体外诱导肝细胞和胰腺细胞的分化,提供了充实的基础和技术支撑。
Jauch博士参与了研发衡量转录因子结合DNA能力的ω因子计算程序,该程序已经在转录因子研究领域被广泛应用。他以第一发明人的两项专利分别在欧洲和美国取得授权。
获奖及荣誉: “通过工程化改造SOX转录因子促进细胞重编程”这一重要成果在第4届国际SOX会议上获得Pevny杰出研究奖(2014年9月获奖);
专利
Jauchr R, Kolatkar PR, Aksoy I, Stanton LW. Mutant Sox Proteins and methods of inducing pluripotency. No. 61/272,793, filed on November 4, 2009
Jauch R, Wahl MC et al. Crystallographic Structure of Mnk2 and Mnk1.(EP 050198899.3). assignee: DeveloGen AG and Max-Planck-Gesellschaft. filing date 13.9.2005
研究领域
Jauch博士非常擅长独立管理多种基础型以及转化型的研究项目,其中包括转录因子的协作,基于结构的药物优化,重新设计多能性重编程因子,药物筛选和调控基因组学;
近期论文
1.Yong-Heng Huang, Aleksander Jankowski , Kathryn S.E. Cheah, Shyam Prabhakar &Ralf Jauch, (2015) SOXE transcription factors form selective dimers on non-compact DNA motifs through multifaceted interactions between dimerization and high-mobility group domains, Scientific Reports, 2015 May 27;5:10398.
2.Narasimhan K, Pillay S, Huang YH, Jayabal S, Udayasuryan B, Veerapandian V, Kolatkar P, Cojocaru V, Pervushin K, Jauch R.(2015) DNA-mediated cooperativity facilitates the co-selection of cryptic enhancer sequences by SOX2 and PAX6 transcription factors,Nucleic Acids Res. 2015 Feb 18;43(3):1513-28
3.Xiaoxiao Yang, Vikas Malik, Ralf Jauch. (2015) Reprogramming cells with synthetic proteins, Asian Journal of Andrology 2015 17, 1–9;
4.Merino, F., Ng, C.K.L., Veerapandian, V., Sch?ler,H.R., Jauch, R. (corresponding author)., Cojocaru V. (2014). Structural Basis for the SOX-Dependent Genomic Redistribution of OCT4 in Stem Cell Differentiation. Structure 2014. In press
5.Aksoy I, Giudice V, Delahaye E, Wianny F, Aubry M, Mure M, Chen J, Jauch R, Bogu GK, Nolden T et al: (2014). Klf4 and Klf5 differentially inhibit mesoderm and endoderm differentiation in embryonic stem cells. Nature communications 2014, 5:3719.
6.Aksoy I. *, Jauch R. *(* shared first author), Eras V., Bin AC., Chen J., Divakar U., Ng CK., Kolatkar PR., Stanton LW. (2013) Sox transcription factors require selective interactions with Oct4 and specific transactivation functions to mediate reprogramming. Stem Cells Dec;31(12):2632-46
7.Jauch, R. (corresponding author). and Kolatkar, P.R. (2013). What makes a pluripotency reprogramming factor? Curr Mol Med May 2
8.Aksoy, I., Jauch, R. (shared first author), Jiaxuan, C., Dyla, M., Bogu, G.K., Divakar, U., Ng, C.K., Yi, R.T., Hutchins, A.P., Kolatkar, P.R. et al. (2013) Oct4 switches partnering from Sox2 to Sox17 and reinterprets the enhancer code to specify primitive endoderm. EMBO J, Apr 3;32(7):938-53. – highlighted in “Have you seen section”
9.Esch, D., Vahokoski J., Goves, M.R., Pogenberg, V., Cojocaru V., Bruch, H., Han, D., Drexler, H.C.A., Arauzo-Bravo, M.J., Ng, C.K.L., Jauch, R., Wilmanns, M., Sch?ler,H.R. (2013) A unique Oct4 interface is crucial for reprogramming to pluripotency. Nature Cell Biol, 2013 Feb 3;15(3):295-301.
10.Sun, W., Hu, X., Lim, M.K., Ng, C.K., Choo, S.H., Kolatkar, P.R., Jauch, R. (corresponding author) and Prabhakar, S. (2013) Estimating protein-DNA binding energies from in vivo binding profiles. Nucl Acids Res, 2013 Apr 16
11.Jankowski, A., Szczurek, E., Jauch R., Tiuryn, J., Prabhakar, S.(2013) Comprehensive Prediction in 78 human cell lines reveals rigidity and compactness of transcription factor dimmers. Genome Research, 2013 Apr 3 Epub
12.Hutchins, A.P., Choo, S.H., Misri, T., Woon, C., Jauch, R. and Robson, P. (2012) Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells. Stem Cells, Feb;31(2):269-81.
13.Hutchins, A.P., Diez, Diego; Takahashi, Y; Ahmad, S,; Jauch, R.; Tremblay, M.; Miranda-Saavedra, D. Differential co-factor recruitment determines STAT3's cell type-independent and cell type-specific functions. Nucleic Acids Res, 2013 Feb 1;41(4):2155-70
14.Yu, L., Pugalenthi, G., Hong, F., Sizun, J., Jauch, R., Stanton, L.W. and Kolatkar, P.R. (2012) Structural Analysis and dimerization profile of the SCAN domain of the pluripotency factor Zfp206 Nucleic Acids Res, 2012 Sep 1;40(17):8721-32
15.Johnson, R., Richter, N., Bogu, G.K., Choo, S.H., Jauch, R. and Stanton, L.W. (2012) A Genome-Wide Screen for Genetic Variants That Modify the Recruitment of REST to Its Target Genes. PLoS Genet 2012 April; 8(4)
16.Ng, C.K.L., Prabhakar, S Kolatkar, P.R. Jauch, R. (corresponding author) (2012). Deciphering the Sox-Partner code by quantitative cooperativity measurements. Nucleic Acids Res 2012 Jun 1;40(11):4933-41
17.Jauch, R. (corresponding author) Ng, C.K.L., Narasimhan, K, Kolatkar, P.R.. (2011). Crystal structure of the Sox4 HMG/DNA complex suggests a mechanism for the positional interdependence in DNA recognition. Biochem J 443(1):39-47
18.Jauch, R. Hutchins, A., Aksoy, I., Ng, C.K.L., Xian, X.F., Palasingam, P., Robson, P., Stanton, W., and Kolatkar, P.R. (2011). Conversion of Sox17 into a Pluripotency Reprogramming Factor by Re-engineering its Association with Oct4 on DNA. Stem Cells Jun;29(6):940-51 Highlighted by Faculty1000
19.Baburajendran, N., Jauch, R, (shared first, corresponding author)., Tan, C and Kolatkar, P.R. (2011). Structural basis for DNA recognition by constitutive Smad4 MH1 dimers. Nucleic Acids Res. Oct;39(18):8213-22
20.Narasimhan, K., Pillay, S., Bin Ahmad, N.R., Bikadi, Z., Hazai, E., Yan, L., Kolatkar, P.R., Pervushin, K.and Jauch, R. (corresponding author) (2011) Identification of a Polyoxometalate Inhibitor of the DNA Binding Activity of Sox2. ACS Chem Biol. Jun 17;6(6):573-81
21.Jauch R (corresponding author), Choo SH, Ng CK, et al. Crystal structure of the dimeric Oct6 (POU3f1) POU domain bound to palindromic MORE DNA. Proteins. 2011. 79(2):674-7
22.Baburajendran, N., Palasingam, P., Narasimhan, K., Sun, W., Prabhakar, S., Jauch, R (corresponding author)., and Kolatkar, P.R. (2010). Structure of Smad1 MH1/DNA complex reveals distinctive rearrangements of BMP and TGF-{beta} effectors. Nucleic Acids Res. Jun;38(10):3477-88
23.Johnson, R., Richter, N., Jauch, R., Gaughwin, P.M., Zuccato, C., Cattaneo, E., and Stanton, L.W. (2010). The Human Accelerated Region 1 noncoding RNA is repressed by REST in Huntington's disease. Physiol Genomics.
24.Palasingam, P., Jauch, R.,(equal contribution, corresponding author), Ng, C.K. & Kolatkar, P.R. The structure of Sox17 bound to DNA reveals a conserved bending topology but selective protein interaction platforms. J Mol Biol. 2009 388, 619-30
25.ohnson, R., Samuel, J., Ng, C.K., Jauch, R., Stanton, L.W., and Wood, I.C. (2009). Evolution of the vertebrate gene regulatory network controlled by the transcriptional repressor REST. Mol Biol Evol 26, 1491-1507.
26.Baburajendran, N., Palasingam, P., Ng, C.K., Jauch, R. and Kolatkar, P.R. (2009) Crystal optimization and preliminary diffraction data analysis of the Smad1 MH1 domain bound to a palindromic SBE DNA element. Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 1105-1109.
27.Ng, C.K., Palasingam, P., Venkatachalam, R., Baburajendran, N., Cheng, J., Jauch, R. and Kolatkar, P.R. (2008) Purification, crystallization and preliminary X-ray diffraction analysis of the HMG domain of Sox17 in complex with DNA. Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 1184-1187.
28.Jauch R, Ng CKL, Saikatendu KS, Stevens RC, Kolatkar PR. Crystal Structure and DNA Binding of the Homeodomain of the Stem Cell Transcription Factor Nanog. J Mol Biol. 2008; 376(3): 758-70.
29.Jauch R, Yeo HC, Kolatkar PR, and Clarke ND. Assessment of CASP7 structure predictions for template free targets. Proteins. 2007; 69 Suppl 8:57-67
30.Jauch, R., Cho, MK, Jakel, S, Netter, C, Schreiter, K, Aicher, B, Zweckstetter, M, Jackle, H and Wahl, MC. Mitogen-activated Protein Kinases Interacting Kinases are Autoinhibited by a Reprogrammed Activation Segment. Embo J. 2006; 25, 4020-4032.
31.Jauch R, J?kel S, Netter C, Schreiter K, Aicher B, J?ckle H and Wahl MC. Structures of Mnk-2 Reveal an Inhibitory Conformation and a Zinc-Binding Site. Structure. 2005;(13): 1559-1568.
32.Jauch R, Humm A, Huber R, Wahl MC. Structures of E. coli NAD Synthetase with Substrates and Product Reveal Mechanistic Rearrangements. J Biol Chem. 2005; 280: 15131 – 15140
33.Jauch R, Bourenkov GP, Chung HR, Urlaub H, Reidt U, Jackle H, Wahl MC. The Zinc Finger-Associated Domain of the Drosophila Transcription Factor grauzone is a Novel Zinc-Coordinating Protein-Protein Interaction Module. Structure. 2003;(11):1393-402.