Department of Biology
Loyola University Maryland
4501 N. Charles Street
Baltimore, MD 21210
Office: DS 147
Office tel: 410-617-2590
Areas of Interest
Epigenetics in Stem Cells, Development, and Cancer
Epigenetics is an area of biology involving the study of how modifications to DNA or alterations in DNA structure without a change to the DNA sequence control cellular processes such as transcription, DNA replication, and repair. Epigenetic mechanisms include chromatin remodeling, DNA methylation, and histone modifications. If DNA has certain modifications or packaging to make it very compact, the cell machinery cannot access the DNA sequence to turn those genes on. If it is loosely packaged, then those genes are able to be activated and that protein product can be made. My research focuses on the role these epigenetic mechanisms have in controlling gene expression in normal differentiation and development, as well as the abnormal state of cancer. Stem cell genes, for example, are very highly active before cells specialize but then they need to be turned off in the differentiated cell because they are no longer needed. If, however, those stem cell genes fail to be sufficiently shut off, development can fail. Alternatively, the rapid growth, ability to change cellular properties, and mobility traits of stem cells could remain present in specialized cells. These stem cell properties in differentiated cells can sometimes give them cancer-like properties. I am particularly interested in the common traits and pathways found in normal stem cells and cancer cells.
In order to study these epigenetic mechanisms in mammals, I utilize molecular, biochemical, and cellular techniques in mouse embryonic stem cells, normal and mutant mice, and human or mouse cancer cell lines. In particular, my research focuses on taking these genes encoding proteins that alter the chromatin (called ‘epigenetic modifier’ genes) out of cells or mice to see what the effect of losing that epigenetic modification has for stem cells and/or the organism. These same epigenetic modifiers are involved in converting one cell type to another or taking a specialized cell all the way back to a stem cell state. Understanding those proteins responsible for controlling which genes are turned on at certain times in development and which ones are turned off is very important for understanding the maintenance of normal homeostasis for the cell and the organism. It is also essential to understanding what goes wrong in abnormal development and disease states like cancer.
Tao, Y., Xi, S., Shan, J., Maunakea, A., Che, A., Briones, V., Lee, E.Y., Geiman, T., Huang, J., Stephens, R., Leighty, R.M., Zhao, K., and Muegge, K. Lsh, chromatin remodeling family member, modulates genome-wide cytosine methylation patterns at non-repeat sequences. Proc. Natl. Acad. Sci. USA, 108:5626-31, 2011.
Zeng, W., Baumann, C., Schmidtmann, A., Honaramooz, A., Tang, L., Bondareva, A., Dores, C., Fan, T., Xi, S., Geiman, T., Rathi, R., de Rooij, D., De La Fuente, R., Muegge, K., Dabrinski, I. Lymphoid specific helicase (Hells) is essential for meiotic progression in mouse spermatocytes. Biol. Reprod., 84:1235-41, 2011.
Geiman, T.M., and Muegge, K.: DNA methylation in Early Development. Mol. Reprod. Dev., 77:105-113, 2010.
Xi, S., Geiman, T.M., Briones, I., Tao, Y., Xu, H., and Muegge, K. Lsh participates in transcriptional silencing of stem cell genes. Stem Cells, 27:2691-2702, 2009.
Zhu, H., Geiman, T.M., Xi, S., Jiang, Q., Schmidtmann, A., Chen, T., Li, E., Muegge, K. Lsh is involved in de novo methylation of DNA. EMBO J., 25:335-345, 2006.
Geiman, T.M., Robertson, A.K, Chen, Y., Mazumdar, M., Kim, W., Yokomori, K., Zhao, Y., and Robertson, K.D. Isolation and characterization of a novel DNA methyltransferase complex linking DNMT3B with components of the mitotic chromosome condensation machinery. Nucleic Acids Res., 32:2716-2729, 2004.
Geiman, T.M., Sankpal, U.T., Robertson, A.K., Zhao, Y., Zhao, Y., and Robertson, K.D. DNMT3B interacts with hSNF2H chromatin remodeling enzyme, HDACs 1 and 2, and components of the histone methylation system. Biochem. Biophys. Res. Commun. 318:544-555, 2004.
Geiman, T.M., Tessarollo, L., Anver, M., Kopp, J.B., Ward, J.M., and Muegge, K.: Lsh, a SNF2 family member, is required for normal murine development. Biochim. et Biophys. Acta. 1526:211-220, 2001.
Geiman, T.M., and Muegge, K.: Lsh, an SNF2/helicase family member, is required for proliferation of mature T lymphocytes. Proc. Natl. Acad. Sci., USA. 97:4772-4777, 2000.