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Alexandra Mims Pike

Class 2011
Education BS, Indiana University
Email amims1@jhmi.edu
Mentor

Dr. Carol Greider

Research Interests

My project focuses on understanding how telomere length equilibrium is maintained in human cells. Telomeres are repetitive DNA and specialized proteins at the end of a chromosome and serve to protect the genome. Every time a cell divides, some telomere sequence is lost. Critically short telomeres elicit a DNA damage response and lead to cell senescence, apoptosis and aging phenotypes. The enzyme telomerase helps by adding telomere repeats back to short telomeres, but it can also be aberrantly activated in human cancers. Because of the relevance of telomere length maintenance in aging and cancer, I am particularly interested in understanding how telomere length is maintained in human cells.

The specialized telomere binding proteins known as the shelterin complex play an important role in both protecting the DNA ends and regulating telomerase activity. In a way that is not yet clear, these proteins communicate with telomerase to convey the status of the telomeres in a cell. In particular, my project aims to determine the role of shelterin component TIN2 in telomere length maintenance. Cells with TIN2 knocked down lose telomere protection and have shown to be elongated by telomerase. Surprisingly, missense mutations in an uncharacterized domain of TIN2 have been identified in patients with the severe short telomere disease Dyskeratosis Congenita. Through cell culture and molecular biology techniques I am using these patient mutations to better understand the role of TIN2 in telomere length maintenance.

Publications

Lee, S.S., Bohrson, C., Pike, A.M., Wheelan S.J., and Greider, C.W. ATM Kinase Is Required for Telomere Elongation in Mouse and Human Cells.Cell Rep. 2015 Nov 24;13(8):1623-32. PMID: 26586427

Waldman, V. M., Stanage, T. H., Mims, A., Norden, I. S. and Oakley, M. G. (2015), Structural mapping of the coiled-coil domain of a bacterial condensin and comparative analyses across all domains of life suggest conserved features of SMC proteins.Proteins, 83: 1027–1045. PMID 25664627

Harris, D. R., Mims, A., and Bunz, F. Genetic disruption of USP9X sensitizes colorectal cancer cells to 5-fluorouracil. Cancer Biol Ther. 2012 Nov;13(13):1319-24. PMID 22895071