Research Assistant Professor of Physiology
Dr. Sheldon did her undergraduate work at the University of New Hampshire where she received a B.A. (1976) in Zoology and did her graduate work at Dartmouth College in the Department of Biology where she was awarded the Ph.D (1990). Her postdoctoral training was at Harvard Medical School in Boston in the Department of Genetics and in the Massachusetts General Hospital in the Department of Molecular Biology (1990-94). Upon returning to Dartmouth she worked with Dr. Allan Munck in the Department of Physiology as a Research Associate until her appointment as a Research Assistant Professor in the department in 1999.
The long-term focus of Dr. Sheldon's research is in understanding the molecular mechanisms underlying steroid hormone receptor-mediated gene regulation and to apply that to understanding the molecular basis of disease that includes cancer and other endocrine-associated diseases. Her focus is on how chromatin structure regulates gene transcription. The primary project in the lab is the identification of histone modifications that are functionally important in modulating chromatin structure at the mouse mammary tumor virus (MMTV) promoter activated by the glucocorticoid receptor (GR). Proteins that are recruited to the MMTV promoter by the GR that mediate these modifications are being identified and the kinetics and coordination of histone modification, and protein interaction at the MMTV promoter are proving significant to transcriptional activation and repression.
A more recently initiated project in the lab is the investigation into whether the environmental toxin arsenic effects gene transcription mediated by GR through histone modification. Environmental levels of arsenic have been implicated in the development of cancer and various metabolic diseases but the molecular mechanisms involved are not understood.
These studies are carried out in cells in culture and in an in vitro chromatin remodeling system. Methods used include basic and advanced molecular techniques utilizing both nucleic acid and protein biochemistry.
Lynn A. Sheldon , Matthias Becker, and Catharine L. Smith. (2001). "Steroid Receptor-Mediated Histone Deacetylation and Transcription at the MMTV-LTR" . J. Biol. Chem. 276: 32423Lynn A. Sheldon, Catharine L. Smith, Jack E. Bodwell, Allan U. Munck, Gordon L. Hager . (1999). "A Ligand Binding Domain Mutation in the Mouse GR Functionally Links Chromatin Remodeling and Transcriptional Activation". Mol. Cell. Biol 19: 8146
Lynn A. Sheldon and Robert E. Kingston. (1993). "Hydrophobic coiled-coil domains regulate the subcellular localization of human heat shock factor 2 ". Genes and Development 7: 1549