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case western reserve university

BIOCHEMISTRY
 
 

Dr. Nikki Harter

Associate Profesor

Pub Med:

Dr. Nikki Harter

Research in the Harter Laboratory focuses on three major areas: (1) Understanding the nature of quiescence in cultured mammalian cells at the level of chromatin structure, (2) the role of chromatin remodeling factors in the differentiation of skeletal muscle cells, and (3) determining the genetic and epigenetic changes that may be relevant to the development of malignant melanoma after UV radiation.

Understanding the organization of chromatin in establishing and maintaining cellular quiescence, the counterpart to proliferation, is critically important for understanding the biology underlying the development of human cancer. Human Adenovirus and one of the proteins it encodes (E1A) is known to induce cells to exit quiescent. We use E1A as a tool to determine what changes in the organization of chromatin are central for re-entry of quiescent cells into the mitotic cycle.

Remarkably little is known about the initiation and maintenance of skeletal muscle differentiation in the context of chromatin function. We are currently studying the role of the myogenic factor MyoD and certain members of the Rb family of proteins (pRb, p130) in helping chromatin-modifying factors in re-organizing chromatin structure in both undifferentiated and differentiated myoblasts.

Melanoma is a lethal skin malignancy of increasing incidence, and numerous studies have pointed to the importance of ultraviolet (UV) radiation in its development. Our goal is to determine whether the UV effect ultimately perturbs chromatin-remodeling pathways at the genetic and/or epigenetic level, thereby leading to the improper activation and/or silencing of genes, and in turn, downstream processes sufficient to induce malignant melanoma.

Selected References

  • Ghosh, M., and Harter, M.L.(2003). A viral mechanism for remodeling chromatin structure in G0 cell. Mol. Cell, 12, 255-260.

    Mal, A., and Harter, M.L. (2003). MyoD is functionally linked to the silencing of a muscle-specific regulatory gene prior to skeletal myogenesis. Proc. Natl. Acad. Sci. USA, 100, 1735-1739.

  • Mal, A., and Harter, M.L. (2003). Mal, A., Sturniolo M., Schliz, L., Ghosh, M., and Harter, M.L. (2001). A role for histone deacetylase HDAC1 in modulating the transcriptional activity of MyoD: Inhibition of the myogenic program. EMBO J., 20, 1739-1753 .

  • Chattapadyah, D., Ghosh, M.K., Mal, A., and Harter, M.L. (2001). Inactivation of p21 by E1A leads to the induction of apoptosis in DNA damaged cells. J. Virol., 75, 9844-9856.

  • Mal, A., Chattapadyah, D., Ghosh, M., Poon, R.Y.C., Hunter, T., and Harter, M. L. (2000). p21 and the retinoblastoma protein control the absence of DNA replication in terminally differentiated muscle cells. J. Cell Biol., 149, 281-292.

  • Mal, A., Poon, R. Y. C., Howe, P.P., Toyoshima, H., Hunter, T., and Harter, M.L. (1996). The E1A oncoprotein disables the CDK inhibitor p27Kip1 in TGF ß treated cells. Nature, 380, 262 265 .

  • Harter, M.L. (1996). Molecules that regulate the cell cycle. Review TLI 2, 3 4.

  • Mal, A., Piotrkowski, A., and Harter, M.L. (1996). Cyclin dependent kinases phosphorylate the adenovirus E1A protein, enhancing its ability to bind pRb and disrupt pRb E2F complexes. J. Virol., 70, 2911 2921.

  • Lundblad, J.R., Kwok, R.P.S., Laurance, M.E., Harter, M.L., and Goodman, R.H. (1995). Adenoviral E1A associated p300 is a functional homologue of the transcriptional co activator CBP. Nature 374, 85-88.

    Stacey, D.W., Dobrowolski, S.F., Piotrkowski, A., and Harter, M.L. (1994). The adenovirus E1A protein overrides the requirement for cellular ras in initiating DNA synthesis. EMBO J., 13, 6107 6114.

  • Dobrowolski, S., Harter, M.L., and Stacey, D.W. (1994). Cellular ras activity is required for passage through multiple points of the G0/G1 phase in BALB/C 3T3 cells. Mol. Cell.Biol., 14, 5441 5449.