许田教授_生物行

许田博士简介(Tian Xu, Ph.D.)
Lab: http://info.med.yale.edu/genetics/xu/focus.html
1962年出生于浙江省嘉兴市。1978－1982年就读于复旦大学谈家祯教授主持的遗传学专业。毕业后留校任教于生物系和遗传学研究所。1983年带50美元来到纽约哈蓝姆穷人区艰苦奋斗。1984年获耶鲁大学奖学金读博士。从师于著名发育遗传学家S. Artavanis-Tsakonas教授研究神经发育分子遗传学机理。1990年获得博士，以其成绩在全美博士毕业生中获20人之一的美国海伦黑—慧特尼(Helen Hay Whitney) 博士后奖。于1990－1993年在加州大学伯克莱分校分子细胞生物系随著名遗传学家GeraldRubin(美国科学院院士)做博士后研究。1993年受聘于耶鲁大学医学院任遗传学、发育生物学、分子肿瘤学助理教授，并兼职于癌症研治中心和Boyer分子医学中心。1998年任副教授，2001年成为耶鲁大学终生教授。

研究主攻方向是用新的遗传学方法鉴别导致疾病基因(如癌症、神经系统功能减退、缺氧症)。建立动物疾病模型、通过研究果蝇、小鼠、人细胞中致病基因功能来寻找发育和疾病的遗传分子调控机理。曾为Nocth信号转导途径研究作出重大贡献。他发明了在全世界数千家果蝇实验室中广泛使用的镶嵌体分析技术，发表文章是在遗传学和发育生物学领域被引用最多的文献之一。他首先发明用镶嵌体技术筛选肿瘤抑制基因等疾病基因，并首创了肿瘤发生和缺氧反应等的果蝇模型。他找到了lats等肿瘤抑制基因家族，发现这些基因的发育生物学功能是调控器官及组织大小，并首先提出了肿瘤发生和器官大小调控有关的理论。近期用果蝇模型发现了结节性硬化综合征疾病基因TSC的功能并确定其参与调控胰岛素信号转导。为治疗结节性硬化和糖尿病提供了新的依据。他在动物疾病模型和器官大小调控理论研究中处于世界领先地位。1994年以来在哈佛、剑桥等众多大学、企业及国际会议应邀讲学80多次。研究成果在Science、Cell、Nature Genetics、Development等杂志发表。撰写学术专著2本。镶嵌遗传筛选法的发明人，拥有６项国际专利。1995年获PEW学者奖。1997年在全美竞争中成为著名休斯医学研究院成员。并获得美国肿瘤学会研究基金、Donaghue医学研究基金、路夕列P·马基托拉斯科研基金、和美国国家卫生总署颁发的研究基金。

在耶鲁大学教学函盖遗传分析、发育生物学、疾病模型、模式生物学、分子肿瘤学、人类遗传疾病学、分子细胞学等课程。其创办并主持的遗传分析课从1998年开创以来一直是耶鲁大学最受欢迎的研究生课。1994年以来在耶鲁大学先后指导13位博士研究生及10位博士后。毕业学生和博士后中已有4位在美国和中国大学任助理教授和副教授 (如明尼苏达大学)。曾任耶鲁大学Boyer分子医学中心、细胞学系、遗传系的多个教授招聘委员会成员，耶鲁大学遗传学系系主任招聘联系委员会成员，遗传学系研究生兼主任。现任耶鲁大学遗传学系研究生指导委员会委员，遗传学系及发育生物部研究生招生委员会主任，耶鲁大学小鼠基因组委员会成员。

1996年以来参加多个国际科学、学术及基金会委员会工作，包括美国科学院美中前沿科学交流委员会，HULL肿瘤研究评奖委员会委员，Leslie－Warner研究基金评委，安娜赫尔博士基金会委员。曾参加中国国家自然科学基金会、意大利Tele Thon科学基金会、加拿大医学研究基金会、以色列科学基金会、台湾中研院青年学者奖、英国Wellcome Trust基金会评审。现任吴瑞协会副会长，北美华人生物科学家学会财务部主任。

关心祖国科学、教育、医药发展。每年多次回国进行教学、研究工作，参加基金评审，主持学术会议。1996年起应谈家祯教授邀请在复旦大学展开工作任客座教授，每年讲授发育遗传学，将耶鲁大学课程移植到中国获得好评。2000年和韩珉教授一起在复旦大学建立发育生物学基地，从事发育和疾病研究，并获得中国国家自然科学基金会功能基因组重点基金。98年任中科院发育研究所客座研究员, 参加中国科学院研究生课教学(2000年分子生物学和细胞生物学，最受欢迎的教师)。2000年起任中国科学院海外评审专家和高等教育出版社《当代科学前沿论坛丛书》专家委员会委员。积极促进中美学术交流, 接受美国科学院院长Bruce Alberts委托组织美中前沿科学学术交流， 97-99任交流委员会成员, 99-00任主席。

The Xu laboratory is interested in utilizing model organisms to understand the molecular mechanisms of human diseases. We are developing and using new genetic approaches to identify genes that are involved in tumorigenesis, metastasis, neurodegeneration, and hypoxia response, and are exploring the developmental and biochemical functions of these genes in Drosophila, mice, and human cells.

BOOKS

Genetic Models in Cardiorespiratory Biology. Ed. Haddad, G. and Xu, T. , Marcel Dekker, Inc. (2001).

Stem Cells and Developmental Biology. Ed. Yi, J.S., Sun, P.F., Tung, X.F. and Xu, T. , M. M. S. Press. (2000).

MANUSCRIPTS

Pagliarini, R.A., and Xu, T. (2003). A genetic screen in Drosophila for metastatic behavior. Science, Oct. 9 Epub ahead of print.

Stewart, R.A., Li, D.M., Huang, H., and Xu, T. (2003). A genetic screen for modifiers of the lats tumor suppressor gene identifies C-terminal Src kinase as a regulator of cell proliferation in Drosophila. Oncogene, 22:6436-6444.

Chen Q, Behar KL, Xu T, Fan C, Haddad GG. (2003). Expression of Drosophila trehalose phosphate synthase in HEK-293 cells increases hypoxia tolerance. J. Biol. Chem., 10: 1074.

Inoki K, Li Y, Xu T, Guan KL. (2003). Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes & Dev. 17:1829-1834.

Pagliarini, R. Quiñones, A., and Xu, T. (2003). Analyzing functions of tumor suppressor genes using a Drosophila model. Methods Mol. Biol., 223:349-382.

Potter CJ, Pedraza LG, Huang H, Xu T. (2003). The tuberous sclerosis complex (TSC) pathway and mechanism of size control. Biochem Soc Trans., 31: 584-586.

Potter CJ, Pedraza LG, Xu T. (2002). Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol., 4: 658-665.

Xia H, Qi H, Li Y, Pei J, Barton J, Blackstad M, Xu T, Tao W. (2002). LATS1 tumor suppressor regulates G2/M transition and apoptosis. Oncogene, 21: 1233-1241.

Zhang S, Xu L, Lee J, Xu T. (2002). Drosophila atrophin homolog functions as a transcriptional corepressor in multiple developmental processes. Cell, 108: 45-56.

Chen Q, Ma E, Behar KL, Xu T, Haddad GG. (2002). Role of trehalose phosphate synthase in anoxia tolerance and development in Drosophila melanogaster. J Biol Chem., 277: 3274-3279.

Yang, X.L., Li, D.M., Chen, W.L., and Xu, T. (2001). Human homologue of Drosophila lats, LATS1, negatively regulate growth by inducing G(2)/M arrest or apoptosis. Oncogene, 20:6516-6523.
Turenchalk, G.S. and Xu, T. (2001). Lats in Cell-cycle Regulation and Tumorigenesis. Encyclopedic Reference of Cancer, pp 492-497. Springer.
Potter, C. J. and Xu, T. (2001).Mechanisms of Size Control. Current Opinions in Genetics & Development , 11:279-286.
Potter, C. J., Huang, H. and Xu, T. (2001). Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell, 105:357-368.
Ma, E., Gu, X.Q., Wu, X.H., Xu, T., and Haddad, G.G. (2001). Mutation in pre-mRNA adenosine deaminase markedly attenuates neuronal tolerance to O2 deprivation in Drosophila melanogaster. J Clin Invest 107:685-693.
Douglas, R.M., Xu, T., and Haddad, G.G. (2001). Cell cycle progression and cell division are sensitive to hypoxia in Drosophila melanogaster embryos. Am J Physiol Regul Integr Comp Physiol 280: R1555-R1563.
Turenchalk, G.S., Potter, C.J., Haddad, G. and Xu, T. (2001). Drosophila as a genetic model system for understanding human biology and disease. Genetic Models in Cardiorespiratory Biology Ed. Haddad, G. and Xu, T., Marcel Dekker, Inc.,
Potter, C.J., Turenchalk, G.S., and Xu, T. (2000). Drosophila in cancer research. An expanding role. Trends Genetics, 16:33-39. Tables for cancer-related genes in Drosophila
Rooke, J.E., Theodosiou, N.A. and Xu, T. (2000). Clonal analysis in the examination of gene function in Drosophila. Methods in Molecular Biology 137: Developmental Biology Protocols III, 15-22.
Xu. R., Cai, J., Xu, T., Zhou, W., Ying B., Deng, K. Zhao, S., and Li, C. (1999). Molecular Cloning and Mapping of A Novel ADAM Gene (ADAM24) to Human Chromosome 4. Genomics, 62:537-9.
Huang, H., Potter, C. J., Tao, W., Li, D.-M., Brogiolo, W., Hafen, E., Sun, H. and Xu, T. (1999). PTEN affects cell size, cell proliferation and apoptosis during Drosophila eye development. Development 126, 5365-5372.
Turenchalk, G.S., St. John, M.A.R., Tao, W., and Xu, T. (1999). The role of Lats in cell cycle regulation and tumorigenesis. Biochimica et Biophysica Acta 1424:M9-M16.
Tao, W., Zhang, S., Turenchalk, G.S., Stewart, R.A., Chang, W., St. John, M.A.R., and Xu, T. (1999). Human homolog of the Drosophila melanogaster lats tumor suppressor modulates CDC2 activity. Nature Genetics, 21:177-181.
St. John, M.A.R., Tao, W., Fei, X., Fukumoto, R., Carcangiu, M.L., Brownstein, D.G., A.F. Parlow, McGrath, J., and Xu, T. (1999). Mice deficient of Lats1 develop soft tissue sarcomas, ovarian tumors and pituitary dysfunction. Nature Genetics, 21:182-186.
Qi, H., Rand, M., Wu, X., Sestan, N., Wang, W., Rakic, P., Xu, T., and Artavanis-Tsakonas, S. (1999). Processing of the Notch ligand Delta by the Metalloprotease Kuzbanian. Science, 283:91-94.
Rooke, J.E. Wu, X.H. and Xu, T. (1999). Cell Interaction During Neural Development. Investigation on Cell Modulation: Signal Transduction, Apoptosis, and Gene Expression.Pp.30-35. Ed. Yi, J.S. et al. Military Medical Science Press (In Chinese).
Ma, E., Xu, T., and Haddad, G.G. (1999) Gene regulation by O2 deprivation: an anoxia-regulated novel gene in Drosophila melanogaster. Molecular Brain Research, 63:217-224.
Theodosiou, N. A., Zhang, S., Wang, W. Y., and Xu, T. (1998). slimb coordinates wg and dpp expression in the dorsal-ventral and anterior-posterior axes during limb development. Development, 125, 3411-3416.
Yavari, R, Adida, C., Brines, M., and Xu, T. (1998). Human Metalloprotease-disintegrin Kuzbanian Regulates Sympathoadrenal Cell Fate in Development and Neoplasia. Human Molecular Genetics, 7:1161-1167.
Theodosiou, N.A. and Xu, T. (1998). Use of the FLP-FRT system to study Drosophila development. Methods, 14,335-365.
Rooke, J.E. and Xu, T. (1998). Positive and negative signals between interacting cells for establishing neuronal fate. Bioessays, 20:209-214.
St. John, M.A.R. and Xu, T. (1997). Understanding Human Cancer In A Fly? American Journal of Human Genetics, 61:1006-1010.
Hu, G., Zhang, S., Vidal, M., Ber, J., Xu, T. and Fearon, E.R. (1997). Mammalian homologs of sina regulate DCC via the ubiquitin-proteasome pathway. Genes & Development, 11:2701-2714.
Haddad, G.G., Sun, Y.-A., Wyman, R.J. and Xu, T. (1997). Genetic basis of tolerance to O2 deprivation in Drosophila melanogaster. Proc. Natl. Acad. Sci. U.S.A., 94:10809-10812.
Rooke, J., Pan, D., Xu, T. and Rubin, G.M. (1996). KUZ, a conserved metalloprotease/disintegrin protein, plays two distinct roles during Drosophila neurogenesis. Science, 273: 1227-1231.
Xu, T., Wang, W., Zhang, S., Stewart, R.A., Yu, W. (1995). Identifying tumor suppressors in genetic mosaics: the Drosophila lats gene encodes a putative protein kinase. Development, 121: 1053-1063.
Xu, T. and Harrison, S. (1994). Mosaic analysis using FLP recombinase. Methods in Cell Biol., 44: 655-682.
Busseau. I., Diederich, R.J., Xu, T. and Artavanis-Tsakonas, S. (1994). A member of the Notch group of interacting loci, deltex encodes a cytoplasmic basic protein. Genetics, 136: 585-596.
Xu, T. and Rubin, G.M. (1993). Analysis of genetic mosaics in developing and adult Drosophila tissues. Development, 117: 1223-1237.
Xu, T., Caron, L. A., Fehon , R.G. and Artavanis-Tsakonas, S. (1992). The involvement of the notch locus in Drosophila oogenesis. Development, 115: 913-922.
Artavanis-Tsakonas, S., Delidakis, C., Fehon, R.G., Hartley, D.A., Herndon, V., Johansen, K.M., Markopoulou, K., Preiss, A., Rebay, I., Scottgale, T.N. and Xu, T. (1990). Notch and the molecular genetics of neuroblast segregation in Drosophila. Mol. Reproduction and Development, 27: 23-27.
Xu, T. and Artavanis-Tsakonas, S. (1990). deltex, a locus interacting with the neurogenic genes, Notch, Delta, and mastermind in Drosophila melanogaster. Genetics, 126: 665-677.
Fehon R.G., Kooh, P.J., Rebay, I., Regan, C.L., Xu, T., Muskavitch, M.A.T. and Artavanis-Tsakonas, S. (1990). Molecular interactions between the protein products of the neurogenic loci Notch and Delta, two EGF-homologous genes in Drosophila . Cell , 61: 523-534.
Xu, T., Rebay, I., Fleming, R.J., Scottgale, T.N. and Artavanis-Tsakonas, S. (1990) The Notch locus and the genetic circuitry involved in early Drosophila neurogenesis. Gen & Devel, 4: 464-475.
Hartley, D.A., Xu, T., Artavanis-Tsakonas, S. (1987). The embryonic expression of the Notch locus of Drosophila melanogaster and the implications of point mutations in the extracellular EGF-like domain of the predicted protein. EMBO J, 6: 3407-3417.
Wharton, K.A., Johansen, K.M., Xu, T., Artavanis-Tsakonas, S. (1985). Nucleotide sequence from the neurogenic locus Notch implies a gene product that shares homology with proteins containing EGF-repeats. Cell ,43: 567-581.
Lin, P.F., Liberman, H.B., Yeh, D.B., Xu, T., Zhao, S.Y., Ruddle, F.H. (1985). Molecular cloning and structural analysis of murine thymidine kinase genomic and cDNA sequences. Mol. Cell. Biol. , 5: 3149-3156.

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许田教授