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315 464-9887

Steven Hanes, PhD

4262 Weiskotten Hall
766 Irving Avenue
Syracuse, NY 13210
史蒂文·哈内斯的电子邮件地址生成了一张图片

CURRENT APPOINTMENTS

LANGUAGES

English

RESEARCH PROGRAMS AND AFFILIATIONS

Biochemistry and Molecular Biology
Biomedical Sciences Program

RESEARCH INTERESTS

发育和疾病中的基因表达,RNA pol II调控,同源异构体基因,脯氨酸异构酶

EDUCATION

Postdoctoral Fellow: Harvard Medical School, 1993
PhD: Brown University, 1988

RESEARCH ABSTRACT

Previous Research

Gene Regulation in Development and Disease我的实验室对细胞在胚胎早期发育和细胞周期中如何控制基因活动感兴趣. 调控的一个关键点是单个基因的RNA拷贝的合成. 这个过程是由RNA聚合酶II (RNA pol II)完成的。. 我们在两种不同的背景下研究RNA pol II(见下文). 我们的发现与理解发生在人类细胞中的类似机制有关, 它的破坏通常与疾病有关.

Homeobox genes一个项目研究了同源盒转录调控因子 Drosophila melanogaster (fruit fly). For example, the homeobox gene called bicoid 指导早期胚胎头部和胸部的发育. Bicoid的工作原理是将RNA pol II招募到选定的靶基因上, 它究竟是如何做到这一点的,是我们研究的主题. 我们的研究结果对于理解同型盒基因如何在正常细胞中起作用以及它们的破坏如何导致某些人类癌症具有重要意义.g. childhood leukemias). 我们还发现了与Bicoid相互作用的蛋白质(Sap18和Bin3). 这些蛋白质在人体中也有对应的蛋白质,我们正试图了解它们是如何起作用的.

Prolyl isomerases: A second project involved a gene called ESS1 in Saccharomyces cerevisiae (酵母),它编码一种被称为脯氨酸异构酶的酶. ESS1 是酵母和细胞生长所必需的吗 ESS1 arrest in mitosis. A counterpart of ESS1 is found in humans and is called PIN1. 我们发现Ess1通过控制RNA pol II的构象起作用. 这种认识可能会导致抗真菌药物的发展(见下文)。. Toward this goal, we isolated ESS1 from Candida albicans and Cryptococcus neoformans, the two major human fungal pathogens. 在这些生物体中,Ess1对毒力很重要, 因此,我们正朝着最终目标努力,以抑制Ess1作为潜在的抗真菌治疗方法.

Current Research

Antifungal Drug Development由于出现对现有抗真菌药物具有耐药性的致病性真菌,危及生命的真菌感染在世界范围内正在增加, 免疫抑制疗法的使用增加以及人口老龄化. 我们正在与业界合作开发新颖、安全、广谱的治疗方法.

阶段分离和对极端环境的进化适应相分离是一种生物物理过程,可能被生物体用来在极端环境中生存. 我们提出,进化力量作用于蛋白质,以调整相分离(集中生物分子),以应对极端温度和其他具有挑战性的环境条件. 这些知识将帮助我们了解微生物在其他不适宜生存的条件下(如南极洲)存活的机制。, 并且可能为如何在寒冷中保存组织提供潜在的见解.

Selected References:

  • Palumbo, R. J., Yang, Y., Feigon, J., and Hanes, S. (2024). Bin3/MePCE甲基转移酶结构域的催化活性对于7SK snRNP功能是必不可少的 Drosophila melanogaster. Genetics, Jan 3, DOI: 10.1093/genetics/iyad203, PMCID: PMC10763541
  • Palumbo, R. J., McKean, N., Leatherman, E., Namitz, K. E. W, Connell, L., Wolfe, A., Moody, K., Gostinčar, C., Gunde-Cimerman, N., Bah, A., and Hanes, S. D. (2022). 极性真菌Ess1-CTD轴的共同进化表明相分离在耐寒性中的作用. Sci Advances Vol 8, Issue 36, eabq3235, 7 Sept, DOI: 10.1126/sciadv.abq3235
  • Namitz, K. E. W. , Zheng, T., Canning, A. J., Alicea-Velazquez, N. L., Castañeda, C. A. and Cosgrove, M. C., and Hanes, S. D. (2021)结构分析表明,Ess1通过二价锚定机制使RNA聚合酶II的羧基端结构域异构化. Nat. Comms Biol. 4:398 http://doi.org/10.1038/s42003-021-01906-8
  • Hanes, S. D. (2015). Prolyl isomerases in gene transcription. (Review) BBA General Subjects (Open Access, published online Oct. 31, 2014).
  • Allepuz-Fuster, P., Martinez-Fernandez, V. Garrido-Godino, A.I, Alonso-Aquado, S. Hanes, S.D., Navarro, F. and Calvo, O. (2014). Rpb4/7促进RNA聚合酶II CTD去磷酸化. Nuc. Acids Res. 42: 13674-88.
  • Hanes, S. D. (2014). Ess1脯氨酸异构酶:RNA聚合酶II转录周期的交通警察. (Review) BBA Gene Regulatory Mechanisms 1839: 316-333.
  • Atencio, D., Barnes, C., Duncan, T. M., Willis, I. M, and Hanes S. D. (2014). 酵母Ess1脯氨酸异构酶控制Swi6和wh5的核定位. Genes, Genomes, Genetics 4: 523-537.
  • Samaranayake, D., Atencio, D., Morse, R., Wade, J.T., Chaturvedi, V., and Hanes, S.D. (2013). Ess1在植物生长、形态发生转换和RNA聚合酶II转录中的作用 Candida albicans. PLoS ONE, March 14, 8(3):e59094.
  • Ma, Z., Atencio D., Barnes, C., DeFiglio, H., and Hanes, S. D. (2012) Ess1脯氨酸异构酶在RNA聚合酶II转录周期中的多重作用. Mol. Cell. Biol. 32: 3594-3607.
  • Cosgrove, M., Ding, Y., Rennie, W. A., Lane, M. J., and Hanes, S. D. (2012). Bin3 RNA甲基转移酶(MePCE)靶向7SK RNA控制转录和翻译. WIRES-RNA (Review) (Wiley) July 12, PMID:22740346
  • Battaile, A. R., Jeronimo, C., Jacques P-E., Laramee, L., Fortin, M-E., Forest, A., Bergeron, M., Hanes, S. D., and Robert, F. (2012). 一个通用的RNA聚合酶II CTD周期是由激酶之间复杂的相互作用精心安排的, phosphatase, and isomerase enzymes along genes. Mol. Cell 45: 158-170.
  • Samaranayake, D. P., and Hanes, S. D. (2011). Milestones in Candida albicans gene manipulation. (Review) Fungal Genet & Biol. 48: 858-865.
  • Singh, N., Morlock, H. and Hanes, S. D. (2011). The Bin3 RNA methyltransferase is required for caudal repression in the Drosophila embryo. Devel. Biol. 352: 104-115.
  • Singh, N., Ma, Z., Gemmill, T., Wu, X., Rossettini, A., Rabeler, C., Beane, O., DeFiglio, H., Palumbo, M., Morse, R. and Hanes, S.D. (2009). Ess1脯氨酸异构酶是通过Nrd1途径终止小的非编码调控rna的转录所必需的. Mol. Cell, 36: 255-266.
  • Li, Z., Li, H-M., Devasahayam, G., Gemmill, T., Chaturvedi, V., Hanes, S. D., and Van Roey, P. (2005). Structure of the Candida albicans Ess1脯氨酸异构酶揭示了一个限制结构域迁移的有序连接区域. Biochemistry 44: 6180-6189.
  • Singh, N., Zhu, W. and Hanes, S. D. (2005). Sap18 is required for the maternal gene bicoid to direct anterior patterning in Drosophila melanogaster. Devel. Biol. 278; 242-254.
  • Lebrecht, D., Foehr, M., Smith, E., Lopes, F. J. P., Vanario-Alonso C. E., Reinitz, J., Burz, D. S., and Hanes, S. D. (2005). 双曲面DNA合作结合对胚胎模式发育至关重要 Drosophila. Proc. Natl. Acad. Sci. USA 102: 13176-13181.
  • Wu, X., Rossettini, A. and Hanes, S. D. (2003). The ESS1 prolyl isomerase and its suppressor BYE1 与RNA pol II相互作用抑制转录伸长 Saccharomyces cerevisiae. Genetics 165: 1687-1702.
  • Devasahayam, G., Chaturvedi, V. and Hanes, S. D., (2002). Ess1脯氨酸异构酶是水稻生长和形态发生转换所必需的 Candida albicans. Genetics 160: 37-48.
  • Zhu, W., Foehr, M., Jaynes, J. B., and Hanes, S. D. (2001). Drosophila SAP18, Sin3/Rpd3组蛋白去乙酰化酶复合体的一个成员与Bicoid相互作用并抑制其活性. Dev. Genes Evol. 211: 109 – 117.
  • Burz, D. S. and Hanes, S. D. (2001). 分离破坏协同DNA结合的突变 Drosophila Bicoid protein. J. Mol. Biol. 305: 219-230.
  • Wu, X., Wilcox, C. B., Devasahayam, G., Hackett, R.L., Arevalo-Rodriguez, M., Cardenas, M., Heitman, J., and Hanes, S. D. (2000). Ess1脯氨酸异构酶与染色质重塑复合体和一般转录机制有关. EMBO J. 19: 3727-3738. (selected for "Editor's Choice" section, Science, 289:833)
  • Burz, D.S., Rivera-Pomar, R., Jackle, H., and Hanes, S.D. (1998). Bicoid的协同DNA结合提供了一种阈值依赖性激活机制 Drosophila embryo. EMBO J. 17: 5998-6009.
  • Lu, K. P., Hanes, S. D., and Hunter, T. (1996). 有丝分裂调节所必需的人多肽-脯氨酸异构酶. Nature 380: 544-547.

 

PUBLICATIONS

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