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Emmanuel Skordalakes

Emmanuel Skordalakes, Ph.D.

Laboratory

The Skordalakes Laboratory

Contact

215-495-6884
skorda@wistar.org

Associate Professor, Gene Expression & Regulation Program

About the Scientist

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 our understanding of the structure and function of this unique reverse transcriptase and in the creation of therapeutics that could inhibit telomerase activity required in more than 85 percent of cancers. 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 an understanding of how the proper function of these factors impacts telomerase function and cell proliferation.

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.

View Publications

The Skordalakes Laboratory

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.

Staff

Postdoctoral Fellows

Bradley Miller, Ph.D.
Sarah Plucinsky, Ph.D.

Graduate Students

Mallorie Fouch
Prashanth Shastrula

Lab Assistant

Vikas Bommineni

Research

Telomerase Function

Telomere replication is mediated by telomerase, an RNA dependent DNA polymerase structurally similar to retroviral reverse transcriptases and viral RNA polymerases. Biochemical studies on telomerase for more than two decades have provided a wealth of information regarding telomerase function and substrate specificity. Despite this information, the biophysical mechanisms underlying telomerase architecture and function are poorly understood. Our goal is to further elucidate the molecular basis of telomere replication by telomerase using structural and biochemical approaches. The information generated here should provide novel insights into the basic mechanisms of telomere replication and length homeostasis. It will further enrich our understanding of the mechanism of DNA replication by polymerases in general. It will provide a framework to design small molecule inhibitors of telomerase that may be of therapeutic value for cancer and other diseases associated with cellular aging.

Telomerase Regulation

In recent years, a number of factors essential for telomerase regulation and telomere maintenance have been identified. The method by which telomerase and associated regulatory factors physically interact and function with each other to maintain appropriate telomere length is poorly understood. 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.

Skordalakes Lab Structure Gallery