Felice Elefant, PhD
Office: PISB 317
Phone: (215) 895-0220
Lab: PISB 312 A
Lab Phone: (215) 895-0573
The Elefant Lab
Epigenetic mechanisms of gene control in neurodevelopment and disease
- BS, George Washington University
- PhD, Temple University
- Post-doctoral fellowship, University of Pennsylvania, Departments of Genetics and Medicine, Howard Hughes Medical Institute
Epigenetic mechanisms of gene control provide both a stable yet flexible system of regulating gene expression at each stage of neurogenesis, thus promoting basic brain and CNS development, while allowing for the neural plasticity that is essential for our different behaviors and cognitive abilities. One such epigenetic modification is histone acetylation that serves to epigenetically “mark” DNA and associated histone proteins within chromatin at distinct sites and patterns over time to drive gene expression profiles in the brain. The identification of a number of neurological disorders that result from histone acetylation misregulation underscores a crucial role for acetylation in proper CNS development. However, the full array of specific histone acetyltransferase (HAT) enzymes that create these marks remain unclear.
My laboratory is focused on understanding the mechanism(s) underlying epigenetic modes of gene control specifically associated with neurogenesis by using novel techniques in Drosophila and rodent models to identify specific HATs that regulate neuronal processes in the brain. We are currently exploring how specific HATs control neuronal processes such as neuroblast formation, axonal outgrowth, and the synaptic plasticity involved in learning and memory, as well as investigating HAT involvement in age related cognitive decline and neurodegenerative disorders previously not known to be epigenetically-linked. We are also developing multicellular models for the screening and identification or epigenetically based pharmacological drugs that can specifically target and modulate these regulators and the neuronal processes they mediate. In addition to providing new biological insight into epigenetic gene control mechanisms underlying neurogenesis, neurodegeneration, and cognitive decline during aging, these studies will be fundamental in exploring the utility of novel epigenetic-based therapeutics to improve healthcare and quality of life in the elderly.
Currently, there are two main projects ongoing in my laboratory: (please see our laboratory website for more information regarding these projects)
- Project 1: TIP60 and Amyloid Precursor Protein in neuronal development
Project 2: An epigenetic role for Tip60 in age-related cognitive decline.
1R01HD057939: “Tip60 and APP in neuronal development”
Elefant, F., Cooke, N.E., Liebhaber, S.A. 2000(a). Targeted recruitment of histone acetyltransferase activity to a locus control region. JBC 275: 13827-13834.
Elefant, F., Su, Y., Liebhaber, S.A., and Cooke, N.E. 2000(b). Patterns of histone acetylation suggest dual pathways for gene activation by a bifunctional locus control region. EMBO J. 19: 6814-6822
Ho, Y., Elefant, F., Cooke, N.E., and Liebhaber, S.A. 2002. A defined locus control region determinant links chromatin domain acetylation with long-range gene activation. Molecular Cell 9: 291-302.
Ho, Y., Elefant, F., Cooke, N.E., and Liebhaber, S.A. 2006. Locus control region transcription is required for long range gene activation. Molecular Cell 23: 365-375.
Zhu, X., Singh, N., Donnelly, C., Boimel, P. and Elefant, F. 2007. The cloning and characterization of the histone acetyltransferase human homolog Dmel\TIP60 in Drosophila melanogaster: Dmel\TIP60 is essential for multicellular development. Genetics 175, 1229-40. Featured as Issue Highlight.
Lorbeck, M.T., Singh, N., Zervos, A., Dhatta, M., Lapchenko, M.,Chen, and Elefant, F. 2010. The histone demethylase Kdm4a controls genes required for male-specific longevity and sex-determination in Drosophila. Gene 450, 8-17.
Singh, N., Lorbeck, M.T., Zervos,A., Zimmerman, J, and Elefant, F. 2010. The histone acetylatransferase Elp3 plays an active role in the control of synaptic bouton expansion and sleep in Drosophila. J. of Neurochemistry 115, 493-504.
Lorbeck, M., Pirooznia, K., Sarthi, J., Zhu, X. and Elefant, F. 2011. Microarray analysis uncovers a role for Tip60 HAT activity in nervous system function and general metabolism. (In press; PLoS one)