个人简介

2001-2006: Postdoctoral Fellow, University of California, Berkeley Ph.D.: Imperial College, University of London (2000) M.Sc.: University College London (University of London) (1992) B.Sc.: Anglia Ruskin University, Cambridge (1991)

研究领域

Biological

The focus of my research lies with protein nucleic acid assemblies that participate in the replication and maintenance of eukaryotic chromosome ends, called telomeres. Telomeres protect chromosome ends from gradual length erosion, prevent end-to-end fusions and recombination, and promote proper chromosome partitioning during meiosis. Telomere length deregulation and telomerase activation are early and perhaps necessary steps in cancer cell evolution. Furthermore, telomerase and telomere dysfunction are thought to contribute to replicative senescence and programmed cell aging. Despite these fundamental roles in maintaining genome integrity and cell fate, surprisingly little is known about the molecular basis of telomere synthesis by telomerase. We are interested in elucidating the mechanism of telomere replication by telomerase and understand how telomere and telomerase binding proteins regulate telomerase activity and protect chromosome ends. The lab primarily uses structural methods coupled with biophysical and biochemical techniques to study the above systems.

近期论文

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LIMD2 is a small LIM-only protein overexpressed in metastatic lesions that regulates cell motility and tumor progression by directly binding to and activating the integrin-linked kinase. Peng H, Talebzadeh-Farrooji M, Osborne MJ, Prokop JW, McDonald PC, Karar J, Hou Z, He M, Kebebew E, Orntoft T, Herlyn M, Caton AJ, Fredericks W, Malkowicz B, Paterno CS, Carolin AS, Speicher DW, Skordalakes E, Huang Q, Dedhar S, Borden KL, Rauscher FJ 3rd. Cancer Res. 2014 Mar 1;74(5):1390-403. Michael Harkisheimer, Mark Mason, Elena Shuvaeva and Emmanuel Skordalakes. 2013. A Motif in the Vertebrate Telomerase N-terminal Linker of TERT Contributes to RNA Binding and Telomerase Activity and Processivity; Structure 21, 1–9, October 8, 2013 Newhart A, Rafalska-Metcalf IU, Yang T, Joo LM, Powers SL, Kossenkov AV, Lopez-Jones M, Singer RH, Showe LC, Skordalakes E, Janicki SM. Single-cell analysis of RNA-mediated histone H3.3 recruitment to a cytomegalovirus promoter-regulated transcription site. J Biol Chem. 2013 Jul 5;288(27):19882-99. PMCID: PMC3707690 Structure of the Human Telomeric Stn1-Ten1 Capping Complex; Bryan C, Rice C, Harkisheimer M, Schultz DC, Skordalakes E.; PLoS One. 2013 Jun 24;8(6). PMCID: PMC3691326 Mason M, Wanat JJ, Harper S, Schultz DC, Speicher DW, Johnson FB, Skordalakes E. Cdc13 OB2 Dimerization Required for Productive Stn1 Binding and Efficient Telomere Maintenance. Structure. 2013 Jan 8;21(1):109-20. PMCID: PMC3545062. Accompanying Review, Marita Cohn; OB Fold Contributes to Telomere Maintenance; Structure, Volume 21, Issue 1, 8 January 2013, Pages 3-4. Skordalakes, E. and Lue, N. F. TERT Structure, Function, and Molecular Mechanisms, in Telomerases: Chemistry, Biology, and Clinical Applications (eds N. F. Lue and C. Autexier), John Wiley & Sons, Inc., (2012), Hoboken, NJ, USA. doi: 10.1002/9781118268667.ch3 Schuller AP, Harkisheimer MJ, Skordalakes E. In vitro Reconstitution of the Active T. castaneum Telomerase. J Vis Exp. 2011 Jul 14;(53). PMCID: PMC3196162 Mason M, Schuller A, Skordalakes E. Telomerase structure function. Curr Opin Struct Biol. 2011 Feb;21(1):92-100. Epub 2010 Dec 17. Review. PubMed PMID: 21168327. Mitchell MT, Smith JS, Mason M, Harper S, Speicher DW, Johnson FB, Skordalakes E. Cdc13 N-terminal dimerization, DNA binding, and telomere length regulation. Mol Cell Biol. 2010 Nov;30(22):5325-34. Epub 2010 Sep 13. PMCID: PMC2976383. Song Y, Willer JR, Scherer PC, Panzer JA, Kugath A, Skordalakes E, Gregg RG, Willer GB, Balice-Gordon RJ. Neural and synaptic defects in slytherin, a zebrafish model for human congenital disorders of glycosylation. PLoS One. 2010 Oct 29;5(10):e13743. PMCID: PMC2966427. Mason M, Skordalakes E. Insights into Cdc13 dependent telomere length regulation. Aging (Albany NY). 2010 Oct;2(10):731-4. PMCID: PMC2993802. Mitchell M, Gillis A, Futahashi M, Fujiwara H, Skordalakes E. Structural basis for telomerase catalytic subunit TERT binding to RNA template and telomeric DNA. Nat Struct Mol Biol. 2010 Apr;17(4):513-8. Epub 2010 Mar 28. PubMed PMID: 20357774. McCray BA, Skordalakes E, Taylor JP. Disease mutations in Rab7 result in unregulated nucleotide exchange and inappropriate activation. Hum Mol Genet. 2010 Mar 15;19(6):1033-47. Epub 2009 Dec 22. PMCID: PMC2830827. Wang AY, Schulze JM, Skordalakes E, Gin JW, Berger JM, Rine J, Kobor MS. Asf1-like structure of the conserved Yaf9 YEATS domain and role in H2A.Z deposition and acetylation. Proc Natl Acad Sci U S A. 2009 Dec 22;106(51):21573-8. Epub 2009 Dec 4. PMCID: PMC2799888. Skordalakes E. Telomerase structure paves the way for new cancer therapies. Future Oncol. 2009 Mar;5(2):163-7. Review. PubMed PMID: 19284375. Skordalakes E. Telomerase and the benefits of healthy living. Lancet Oncol. 2008 Nov;9(11):1023-4. Gillis AJ, Schuller AP, Skordalakes E. Structure of the Tribolium castaneum telomerase catalytic subunit TERT. Nature. 2008 Oct 2;455(7213):633-7. Epub 2008 Aug 31. Carlson BL, Ballister ER, Skordalakes E, King DS, Breidenbach MA, Gilmore SA, Berger JM, Bertozzi CR. Function and structure of a prokaryotic formylglycine-generating enzyme. J Biol Chem. 2008 Jul 18;283(29):20117-25. Epub 2008 Apr 4. PMCID: PMC2459300. Rouda S, Skordalakes E. Structure of the RNA-binding domain of telomerase: implications for RNA recognition and binding. Structure. 2007 Nov;15(11):1403-12. Young TA, Skordalakes E, Marqusee S. Comparison of proteolytic susceptibility in phosphoglycerate kinases from yeast and E. coli: modulation of conformational ensembles without altering structure or stability. J Mol Biol. 2007 May 18;368(5):1438-47. Epub 2007 Mar 6. Skordalakes E, Berger JM. Structural insights into RNA-dependent ring closure and ATPase activation by the Rho termination factor. Cell. 2006 Nov 3;127(3):553-64. Skordalakes E, Brogan AP, Park BS, Kohn H, Berger JM. Structural mechanism of inhibition of the Rho transcription termination factor by the antibiotic bicyclomycin. Structure. 2005 Jan;13(1):99-109. Daganzo SM, Erzberger JP, Lam WM, Skordalakes E, Zhang R, Franco AA, Brill SJ, Adams PD, Berger JM, Kaufman PD. Structure and function of the conserved core of histone deposition protein Asf1. Curr Biol. 2003 Dec 16;13(24):2148-58. Skordalakes E, Berger JM. Structure of the Rho transcription terminator: mechanism of mRNA recognition and helicase loading. Cell. 2003 Jul 11;114(1):135-46. Hansen CL, Skordalakes E, Berger JM, Quake SR. A robust and scalable microfluidic metering method that allows protein crystal growth by free interface diffusion. Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16531-6. Epub 2002 Dec 16. PMCID: PMC139178.