Margaret C. Neville Professor of Physiology and Biophysics, Professor of Obstetrics and Gynecology Chief, Section on Basic Reproductive Science Ph.D., University of Pennsylvania UCHSC at Fitzsimons RC-1 North Tower, P18-5101 PO Box 6511, Mail Stop F8307 Tel (303) 724-3505, Fax (303) 724-3512 Peggy.Neville@UCHSC.edu

The major interest of my laboratory is the regulation of the development of the normal mammary gland. We are currently involved in three areas of investigation:

1. The regulation of lipid synthesis in the mammary gland. Here our focus is the mechanisms by which triglyceride is synthesized and secreted into milk. We are particularly interested in the role of the transcription factor SREBP-1 in regulating fatty acid synthesis and whether it plays a role in regulating lipid synthesis in breast cancer cells. We will be using transgenic mice with defects in this pathway to dissect molecular mechanisms of action.
2. Molecular mechanisms bywhich progesterone withdrawal activates milk secretion during the transition from pregnancy to lactation. We are currently using microarray analysis toidentify candidate regulatory genes that coordinate the cellular response to progesterone withdrawal resulting in the secretion of copious quantities of milk. We have identified three candidate genes, IGFBP5, Wnt 5B and TGF-beta3 to mediate the progesterone response. We plan to use transgenic and KO mice mice to elucidate the mechanism by which these agents act.
3. Analysis of lactation defects in transgenic mice. We are currently analyzing the mechanisms by which lactation defects arise in mice overexpressing constitutively active Akt/PKB, human protein C, PKN and IGFBP5 as well as mice with a mammary specific deletion of the gene encoding HIF1". 4. Analysis of tight junction regulation in the mammary alveolar cell. We are currently defining the role of the claudins, transmembrane molecules thought to be important in cell-cell adhesion mediated at the tight junction, in the closure of tight junctions during the transition from pregnancy to lactation.

Since the pregnancy-lactation developmental cycle protects against breast cancer we believe the results of our studies are relevant both to the normal function of the mammary gland and its progression into breast cancer. Much of our work is carried out in animals, but cell culture models are also under study.

Selected Publications

McManaman, J. L., Palmer, C. , Wright, R.M. and Neville, M.C. Functional regulation of xanthine oxidoreductase expression and localization in the mammary gland; Evidence for a role in lipid secretion. J Physiol. 2002 Dec 1;545(Pt 2):567-79.

Russell,T.D., Fischer, A, Beeman, N.E., Freed, E.F., Neville, M.C., Schaack, J. Transduction of the Mammary Epithelium with Adenoviral Vectors in vivo. J Virol. 2003 May;77(10):5801-9.

Rudolph, M.C., McManaman, J.L., Hunter, L., Phang,T., Neville, M.C. (2003) Initiation of Lactation in the Murine Mammary Gland: Temporal analysis of a complex biological switch with expression profiling and trajectory clustering. Journal of Mammary Gland Biology and Neoplasia, In press.

Neville, M.C., McFadden, T.B., Forsyth, I. Hormonal regulation of mammary differentiation and milk secretion. J Mammary Gland Biol Neoplasia. 2002 Jan;7(1):49-66. Review.

McManaman, J. and Neville, M.C. Mammary Physiology and Milk Secretion, Adv Drug Deliv Rev. 2003 Apr 29;55(5):629-41. Review.

Latest Publications in PubMed