Our Science – Sterneck Website

Esta Sterneck, Ph.D.

Laboratory of Cell and Developmental Signaling Head, Molecular Mechanisms in Development Group Investigator Molecular Mechanisms in Development, Group Building 560, Room 22-45 NCI-Frederick Frederick, MD 21702-1201 Phone:   301-846-1471 Fax:   301-846-1666 E-Mail:   sterneck@mail.ncifcrf.gov

Biography

Dr. Esta Sterneck received her Ph.D. in 1992 from the University of Heidelberg following training with Drs. Thomas Graf and Achim Leutz at the European Molecular Biology Laboratory and the ZMBH Center for Molecular Biology, Heidelberg, Germany. She was then recruited as a postdoctoral fellow by Dr. Peter F. Johnson at the ABL-Basic Research Program in Frederick. Dr. Sterneck began her appointment as a principal investigator at the NCI-Frederick in 1998 upon successful competition for an NCI scholarship, and was recruited into a tenure track position in 2003.

Research

Cell Growth Control by C/EBPbeta and C/EBPdelta Transcription Factors

The Ccaat/enhancer binding protein (C/EBP) family of transcription factors consists of five members with similar DNA-binding specificity that form homo- and heterodimers with each other. Our lab investigates the role of C/EBP transcription factors in the regulation of cell growth and differentiation using mouse models and cell culture systems, with current emphasis on the molecular mechanisms of cell death signaling in mammary epithelial and breast tumor cells by the C/EBPdelta transcription factor.

In the human breast, C/EBPdelta expression is detectable in healthy tissue, declines with neoplastic progression and is undetectable in malignant and metastatic disease. Recently, a prospective analysis of early tumors correlated expression of CEBPD with patient survival suggesting that C/EBPdelta is protective. C/EBPdelta can inhibit growth of various human tumor cell lines in vitro. In the mouse mammary gland, C/EBPdelta participates in initiation of apoptosis at the onset of post lactational involution of the epithelial tissue (Thangaraju et al., 2005). C/EBPdelta is also expressed in (limbal) stem cells where it attenuates proliferation. Overwhelmingly, the data point to an important tumor suppressor role of C/EBPdelta by its ability to restrict growth or induce cell death. However, very little is known about the molecular mechanisms by which C/EBPdelta carries out these functions.

Current projects include identification and functional analysis of critical protein interactions and target genes. We are investigating the role of C/EBPdelta in tumorigenesis with various mouse models and by analysis of human breast tumor tissue. Furthermore, we are studying the regulation of C/EBPdelta expression in order to identify small molecules and devise therapeutic strategies that can induce its expression in tumor cells.

The C/EBPbeta gene is essential for mammary epithelial cell proliferation and differentiation during pregnancy and lactation (Robinson et al., 1998). C/EBPbeta-null mice display multiple pathologies, including ovarian and immune system dysfunctions, which preclude proper analysis of specific phenotypes. In order to improve our mouse model, we have generated mice that allow for conditional deletion of the C/EBPbeta gene. These are currently used to further address the role of this gene at specific stages of mammary gland development and carcinogenesis.

Our long term goal is to gain insight into general molecular mechanisms of cell growth control and analyze pro-apoptotic signaling pathways that could be exploited for therapeutic purposes.


Current collaborators include: Dr. Mark Raffeld (Laboratory of Pathology, NCI, Dr. Stefan Ambs (Laboratory of Human Carcinogenesis, NCI), Dr. Bruce Crise (Gene Expression Laboratory, NCI), Dr. Timothy Veenstra (Laboratory of Proteomics and Analytical Technologies, SAIC-Frederick), Dr. Lothar Hennighausen (Laboratory of Mammalian Genetics, NIDDK), Dr. Lane Christenson (University of Kansas Medical Center), Dr. Cynthia Zahnow (Johns Hopkins University), Dr. Robert C. Smart (North Carolina State University), Dr. V. Ganapathy (Medical College of Georgia)Dr. Zdenek Kleibl (Charles University Prague, Czech Republic), Dr. Achim Leutz (Max Delbrueck Center for Molecular Biology, Berlin Buch, Germany).

This page was last updated on 6/12/2008.