NARDULLI, Ann

A major focus of our laboratory is to delineate mechanisms involved in regulating estrogen responsive genes. We are, in particular, interested in studying the interaction of the estrogen receptor with target DNA and in identifying novel regulatory proteins that are associated with the DNA-bound receptor and influence estrogen-mediated transactivation.

The estrogen receptor, like other steroid hormone receptors, plays a role in developmental processes and maintenance of hormone responsiveness in target cells. From the molecular viewpoint, interaction of the estrogen receptor with target genes is of paramount importance in maintaining normal cell function, but is also involved in regulation of mammary tumor cell function.

We are using in vitro and in vivo approaches to study the interaction of the estrogen receptor with DNA and the recruitment of proteins to the DNA-bound receptor. In vitro assays are utilized to examine the interaction of the estrogen receptor with the regulatory proteins we have identified and to determine their effects on receptor function. The estrogen receptor-associated proteins we have identified have a wide range of activities. They alter the ability of the receptor to interact with DNA, survey the genome for damage, inititate DNA repair, remodel chromatin, limit histone acetylation, serve as molecular chaperones, and influence the acetylation and phosphorylation state of the receptor. In vivo assays are utilized to confirm the association of these novel proteins with native gene sequences and to monitor their expression in normal mammary cells and in mammary tumors. These studies will provide new information about the function of receptor-associated proteins and help to define mechanisms regulating estrogen-responsive genes in normal mammary cells and in mammary tumors.

Key Words Recombinant DNA, Introduction of DNA into Animal Cells, Gene Expression Systems, DNA-Protein Interaction, Hormones, Animal Cell and/or Tissue Culture, Site-Directed Mutagenesis, Protein Purification and Characterization, Active Sites and Receptors