Steven Hanes博士

研究抽象

先前的研究

发育与疾病中的基因调控: My laboratory is interested in how cells control the activity of genes during early development of the embryo and during the cell cycle. One key point of regulation is the synthesis of an RNA copy of individual genes. This process is carried out by RNA polymerase II (RNA pol II). We study RNA pol II in two distinct contexts (see below). Our findings are relevant to understanding similar mechanisms that occur in human cells, and whose disruption is often associated with disease.

同源框基因: One project investigated homeobox transcription regulators in 黑腹果蝇 (fruit fly). 例如，同型盒基因叫做 bicoid directs development of the head and thorax in early embryos. Bicoid works by recruiting RNA pol II to selected target genes, and how exactly it does this was the subject of our work. Our results have been important for understanding how homeobox genes function in normal cells and how their disruption causes certain human cancers (e.g. 儿童白血病). We also discovered proteins that interact with Bicoid (Sap18 and Bin3). These proteins have human counterparts and we are trying to understand how they function.

Prolyl异构酶第二个项目涉及一种名为 ESS1 in 酿酒酵母 (yeast), which encodes an enzyme known as a prolyl-isomerase. ESS1 is essential for growth in yeast and cells that lack ESS1 有丝分裂阻滞. 的对应物 ESS1 在人体中发现的，叫做 PIN1. We discovered that Ess1 works by controlling the conformation of RNA pol II. This understanding might lead to the development of antifungal drugs (see below). 为了这个目标，我们孤立了 ESS1 from 白色念珠菌 and 新型隐球菌两种主要的人类真菌病原体. Ess1 in these organisms is important for virulence, so we are working toward an eventual goal of targeting Ess1 for inhibition as a potential antifungal treatment.

目前的研究

抗真菌药物开发: Life-threatening fungal infections are increasing world-wide due to emergence of pathogenic fungi resistant to existing antifungal drugs, and the increased use of immunosuppressive therapies and aging populations. We are collaborating with industry to develop novel, safe, broad-spectrum therapeutics.

Phase separation and evolutionary adaptation to extreme environments: Phase separation is a biophysical process that might be used by organisms to survive in extreme environments. We proposed that evolutionary forces work on proteins to tune phase separation (which concentrates biomolecules) in response to temperature extremes and other challenging environmental conditions. This knowledge will help us understand mechanisms that enable microbial life in otherwise inhospitable conditions (such as Antarctica), and could potentially provide insight into how to preserve tissues in the cold.

选择引用:

• Palumbo, R. J., Yang, Y., Feigon, J.哈内斯，S. (2024). Catalytic activity of the Bin3/MePCE methyltransferase domain is dispensable for 7SK snRNP function in 黑腹果蝇. Genetics， 1月3日DOI: 10.1093/遗传学/iyad203, PMCID: PMC10763541
• Palumbo, R. J., McKean, N.莱瑟曼，E., Namitz, K. E. W，康奈尔，L., Wolfe, A., Moody, K.gostinar, C.纽约州冈德-西曼尔曼., Bah, A.哈内斯，S. D. (2022). Co-evolution of the Ess1-CTD axis in polar fungi suggests a role for phase separation in cold tolerance. 科学的进步 Vol 8，第36期，eabq3235, 9月7日 DOI: 10.1126 / sciadv.abq3235
• Namitz, K. E. W. , Zheng, T.坎宁，A. J.艾丽西亚-委拉斯开兹，n.n. L.， Castañeda, C. A. 和M .科斯格罗夫. C.哈内斯，S. D. (2021) Structure analysis suggests Ess1 isomerizes the carboxy-terminal domain of RNA polymerase II via a bivalent anchoring mechanism. Nat. Comms Biol. 4:398 http://doi.org/10.1038/s42003-021-01906-8
• Hanes, S. D. (2015). 基因转录中的脯氨酸异构酶. (Review) 工商管理学士通识科目 (开放获取，10月10日在线发布. 31, 2014).
• Allepuz-Fuster P.马丁内斯-费尔南德斯，V. Garrido-Godino,.我，阿隆索-阿奎多，S. Hanes, S.D.纳瓦罗，F. 卡尔沃，O. (2014). Rpb4/7 facilitates RNA polymerase II CTD dephosphorylation. Nuc. Acids Res. 42: 13674-88.
• Hanes, S. D. (2014). The Ess1 prolyl isomerase: Traffic cop of the RNA polymerase II transcription cycle. (Review) BBA基因调控机制 1839: 316-333.
• Atencio, D.巴恩斯，C.邓肯，T。. M.，威利斯，我. M，和S. D. (2014). The yeast Ess1 prolyl isomerase controls Swi6 and Whi5 nuclear localization. 基因，基因组，遗传学 4: 523-537.
• Samaranayake D.D . Atencio., Morse, R., Wade, J.T.查图维迪，V.哈内斯，S.D. (2013). Role of Ess1 in growth, morphogenetic switching, and RNA polymerase II transcription in 白色念珠菌. PLoS ONE[j] .浙江农业学报，2014,8(3):59094.
• Ma, Z., Atencio D.巴恩斯，C.DeFiglio, H.哈内斯，S. D. (2012) Multiple Roles for the Ess1 Prolyl Isomerase in the RNA Polymerase II Transcription Cycle. Mol. Cell. Biol. 32: 3594-3607.
• Cosgrove, M., Ding, Y., Rennie, W. A., Lane, M. J.哈内斯，S. D. (2012). The Bin3 RNA methyltransferase (MePCE) targets 7SK RNA to control transcription and translation. WIRES-RNA (回顾)(Wiley) 7月12日，PMID:22740346
• Battaile, A. R.杰罗尼莫，C.雅克·p·e.拉里米，L.福廷，M-E., Forest, A.Bergeron, M., Hanes, S. D.罗伯特，F. (2012). A universal RNA polymerase II CTD cycle is orchestrated by complex interplays between kinase, phosphatase, 以及基因上的异构酶. Mol. Cell 45: 158-170.
• Samaranayake D. P.哈内斯，S. D. (2011). 里程碑 白色念珠菌 基因操作. (Review) 真菌麝猫 & Biol. 48: 858-865.
• Singh, N.莫洛克. 哈内斯，S. D. (2011). Bin3 RNA甲基转移酶是 caudal 政府的镇压 Drosophila embryo. Devel. Biol. 352: 104-115.
• Singh, N., Ma, Z.吉米尔，T., Wu, X.罗塞蒂尼，A.拉贝勒，C., Beane, O.DeFiglio, H.帕伦坡，M., Morse, R. 哈内斯，S.D. (2009). The Ess1 prolyl isomerase is required for transcription termination of small non-coding regulatory RNAs via the Nrd1 pathway. Mol. Cell, 36: 255-266.
• Li, Z., Li, H-M.Devasahayam G.吉米尔，T.查图维迪，V., Hanes, S. D.Van Roey, P. (2005). 结构 白色念珠菌 Ess1 prolyl isomerase reveals a well-ordered linker region that restricts domain mobility. 生物化学 44: 6180-6189.
• Singh, N., Zhu, W. 哈内斯，S. D. (2005). Sap18 是母体基因所必需的 bicoid 引导向前的模式 黑腹果蝇. Devel. Biol. 278; 242-254.
• Lebrecht, D., Foehr, M., Smith, E., Lopes, F. J. P.Vanario-Alonso C. E.赖尼茨，J., Burz, D. S.哈内斯，S. D. (2005). Bicoid cooperative DNA binding is critical for embryonic patterning in Drosophila. Proc. Natl. Acad. Sci. USA 102: 13176-13181.
• Wu, X.罗塞蒂尼，A. 哈内斯，S. D. (2003). The ESS1 脯氨酸异构酶及其抑制因子 BYE1 interact with RNA pol II to inhibit transcription elongation in 酿酒酵母. Genetics 165: 1687-1702.
• Devasahayam G.查图维迪，V. 哈内斯，S. D., (2002). The Ess1 prolyl-isomerase is required for growth and morphogenetic switching in 白色念珠菌. Genetics 160: 37-48.
• Zhu, W., Foehr, M., Jaynes, J. B.哈内斯，S. D. (2001). Drosophila SAP18, a member of the Sin3/Rpd3 histone deacetylase complex interacts with Bicoid and inhibits its activity. Dev. Genes Evol. 211: 109 – 117.
• Burz, D. S. 哈内斯，S. D. (2001). Isolation of mutations that disrupt cooperative DNA binding by the Drosophila Bicoid蛋白质. J. Mol. Biol. 305: 219-230.
• Wu, X., Wilcox, C. B.Devasahayam G.哈克特，R.L.阿雷瓦洛-罗德里格斯，M.卡德纳斯，M.海特曼，J.哈内斯，S. D. (2000). The Ess1 prolyl-isomerase is linked to chromatin remodeling complexes and the general transcription machinery. EMBO J. 19: 3727-3738. (选择在“编辑选择”部分， Science, 289:833)
• Burz, D.S.R . Rivera-Pomar., Jackle, H.哈内斯，S.D. (1998). Cooperative DNA binding by Bicoid provides a mechanism for threshold-dependent activation in the Drosophila embryo. EMBO J. 17: 5998-6009.
• Lu, K. P., Hanes, S. D.亨特，T. (1996). A human peptidyl-prolyl isomerase essential for regulation of mitosis. Nature 380: 544-547.