Positions

Professor
Baylor College of Medicine
Charles C. Bell Professor
Molecular and Cellular Biology

Education

BA from Williams College
PhD from State University of New York at Buffalo
Post-Doctoral Fellowship at Vanderbilt University School of Medicine

Professional Interests

  • Developmental and hormonal regulation of mammary gland gene expression and breast cancer

Professional Statement

The research objectives of my laboratory are to elucidate the mechanisms regulating the normal development of the mammary gland, including the hormonal control of milk protein gene expression, and to determine how these regulatory mechanisms have deviated in breast cancer.

Critical periods of postnatal development in the mouse mammary gland include ductal proliferation and branching that occur during sexual maturity, lobuloalveolar proliferation that occurs during pregnancy, terminal differentiation that results in lactation, and involution characterized by increased apoptosis and extensive tissue remodeling. Studies of the role of systemic hormones (viz., prolactin, glucocorticoids, estrogens and progestins) and local growth factors, including members of the Wnt, Fgf, and IGF families, on each of these processes are under way. The role of specific transcription factors and their dominant-negative isoforms, including members of the C/EBP, Stat and NF I families, are also being examined using transgenic and knockout mouse models. Gene arrays and subtractive hybridization techniques are employed to identify downstream targets of these transcription factors. Postnatal mammary gland development is being studied in knockout mice displaying late embryonic or neonatal mortality by transplantation of mammary epithelium into the cleared mammary gland fat pad of syngeneic recipients. Genetically engineered mice coupled with FACS analysis and transplantation into the cleared mammary fat pad has also been employed as model system in which to isolate and characterize functional mammary progenitors and stem cells. Finally, transgenic and knockout mouse models are being used to elucidate changes in normal mammary gland stem cells and progenitors and signal transduction pathways that are involved in the progression from the normal mammary gland to preneoplasias, as well as the role of mutant p53 and Chk1 in genomic instability and the development of aneuploidy.

Selected Publications