Jeffrey L. Doering
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Professor |
RESEARCH INTERESTS
The currently available human genome sequence does not include the heterochromatic regions, although these sequences comprise 10-15% of the genome. Containing long domains of tandemly repetitious sequences, heterochromatic regions of the genome are important to the functioning of centromeres, telomeres and the control of gene expression in the interphase nucleus. We have constructed a detailed physical map of the centromere and short arm of human chromosome 21 (HC21p) as a model for understanding the organization of heterochromatic genomic regions. The map shows that the structure of HC21p is highly complex, with clusters of a large number of tandemly repeated sequences interspersed with “islands” of low copy number sequences.
Recent work has shown that the repetitive sequences found on HC21p are transcriptionally active in a variety of cancer cells, but inactive in normal tissue. We are trying to use this activity to develop cancer biomarkers for prostate cancer. In particular, we are determining which specific repetitive sequence families most commonly become active in the cancer cells and at which stages of tumor progression. The epigenetic marks of DNA methylation and histone modifications are being used to assay the repetitive sequences for their potential activity. Preliminary results indicate that several of the HC21p repetitive sequences reproducibly exhibit low levels of DNA methylation and thus activity potential in the tumor cells. Studies are ongoing to examine more of the repetitive sequences in a larger sample of cancer cells.
REPRESENTATIVE PUBLICATIONS
Ziccardi, William, Chongjian Zhao, Valery Shepelev, Lev Urlasky, Ivan Alexandrov, Tatyana Andreeva, Evgeny Rogaev, Christopher Bun, Emily Miller Catherine Putonti and Jeffrey Doering. 2016. Clusters of alpha satellite on human chromosome 21 are dispersed far onto the short arm and lack ancient layers. Chromosome Research 24(3): 421-436. doi:10.1007/s10577-016-9530-z
Baaj, S., Rafidi, G., Krueger, J., Chan, E., Vicker, E., Elfar, A. and Doering, J.L. 2014. 6 kb tandem repeat sequence in Homo sapiens. Repbase Reports 14(7):2086-2086.
Bun, Christopher, William Ziccardi, Jeffrey Doering and Catherine Putonti. 2012. MiIP: The monomer identification and isolation program. Evolutionary Bioinformatics 8: 293-300.
Ennesser, R.E. and Doering, J.L. 2011. Beta satellite core sequence in Homo sapiens. Repbase Reports 11(3):1123-1123.
Korenberg, J.R., J. Aaltonen, C. Brahe, D. Cabin, N. Creau, J.M. Delabar, J. Doering, K. Gardiner, R.S. Hubert, J. Ives, A. Kessling, J. Kudoh, R. Lafreniere, Y. Murakami, M. Ohira, M. Ohki, D. Patterson, M.C. Potier, J. Quackenbush, R.H. Reeves, Y. Sakaki, N. Shimizu, E. Soeda, C. Van Broeckhoven, and M.L. Yaspo. 1997. Report and abstracts of the Sixth International Workshop on Human Chromosome 21 Mapping 1996. Cytogenet. Cell Genet. 79:21-52.
