Emmanuel Skordalakes, Ph.D.
The laboratory of Emmanuel Skordalakes studies the complex protein assemblies that participate in the replication and maintenance of chromosome ends, known as telomeres. Telomeres protect the chromosome ends from gradually eroding during DNA replication and they prevent chromosomes from fusing and recombining thus providing the genomic stability required for cell viability. Telomeres do, however, gradually become shorter, a process that is partly responsible for the aging process. Furthermore, telomere length deregulation is a hallmark—and perhaps necessary part—of the cancer cell evolution. The Skordalakes laboratory uses mostly structural, biochemical and cell-based assays to elucidate the function of telomerase, the enzyme that is mainly responsible for telomere replication, and its associated proteins. The laboratory is also interested in identifying small molecule modulators of telomerase activity as potential therapeutics for cancer and age-related diseases.
Skordalakes joined The Wistar Institute in 2006. As an undergraduate, he majored in chemistry at the Anglia Ruskin University in Cambridge, and earned a master's degree in chemical research at University College London of the University of London. In 2000, he received his Ph.D. from Imperial College, University of London, and obtained a postdoctoral fellowship in the Department of Molecular & Cell Biology at the University of California, Berkeley.
Since becoming a member of the Wistar faculty, Skordalakes has made great strides in the study of telomerase. In 2008, the Skordalakes laboratory published the structure of the active region of telomerase, an important milestone in the creation of therapeutics that could inhibit telomerase activity. Since then, Skordalakes and his colleagues have continued their structural studies on the accessory proteins associated with telomerase that help regulate the enzyme's activities. Structural and biochemical characterization of these factors, both in isolation and in complex with one another will facilitate our understanding of how the proper function of these factors impacts telomerase function and cell proliferation.
1. Michael Harkisheimer, Mark Mason, Elena Shuvaeva and Emmanuel Skordalakes. 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.
2. 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).
3. 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.
4. 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.
5. 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.
6. Gillis AJ, Schuller AP, Skordalakes E. Structure of the Tribolium castaneum telomerase catalytic subunit TERT. Nature. 2008 Oct 2;455(7213):633-7.