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Department of Physiology and Biophysics

University of Colorado Department of Physiology and Biophysics
 

Margaret C. Neville, Ph.D.

Professor Emerita

Department of Physiology & Biophysics

UCD Anschutz Medical Campus
RC-1 North Tower, P18-5101
Mail Stop 8307
Tel (303) 724-3505
Fax (303) 724-3512

E-mail:
peggy.neville@ucdenver.edu

BNAT program member

RESEARCH

MAMMARY GLAND BIOLOGY AND MILK SECRETION

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 are using transgenic mice with defects in this pathway and dietary lipid to dissect molecular mechanisms of action.
  2. Molecular mechanisms by which progesterone withdrawal activates milk secretion during the transition from pregnancy to lactation. We are currently using microarray analysis to identify 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 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.

Projects within all these areas of investigation are available to trainees.

ARRAY DATA: JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 2003
1. Presumptive Stromal Genes.
2. Chip Quality Control Data.

Patti Webb
Neuroscience Graduate Student, Senior PRA

E-mail: Patti.Webb@ucdenver.edu

Patti Webb is working on a model system for mammary acini that mimics the hormone responses of the in vivo mammary gland. The goal of these experiments is to define the molecular mechanisms by which the mammary gland responds to insulin in pregnancy.

Heidi Wilson, Ph.D.
Postdoctoral Fellow

E-mail: Heidi.Wilson@ucdenver.edu

Heidi Wilson is investigating a 5 amino acid peptide mimic of a conserved site in several classic claudins that causes apoptosis of mammary epithelial cells when applied at low doses. She postulates that this peptide sets in motion a train of events that cells use to defend against pathogens that attack tight junction complexes in mammary epithelial cells.


Selected Publications

Research Papers:

  • Monks, J. and Neville, M.C. (2004) Albumin transport across the epithelium of the lactating mouse mammary gland.  J. Physiol. . 560: 267-80.. pdf
  • Blackman, B., Russell, T., Nordeen, S.K., Medina, D., Neville, M.C. (2005)  Claudin-7 expression and localization in the normal murine mammary gland and murine mammary tumors.  Breast Cancer Res.  7:R248-255. pdf
  • Rudolph, M.C.; McMamaman, J.L., Phang,T., Russell, T.A., Kominsky, D.J.,  Serkova, N.J., Anderson S.M., Neville, M.C. (2007)  Metabolic regulation in the lactating mouse: A milk lipid synthesizing machine.  Physiological Genomics. 28: 323-326. pdf
  • Anderson, S.M., Rudolph, M.C.,  McManaman, J.L., and Neville, M.C. (2007)  Secretory activation in the mammary gland: It’s not just about milk protein synthesis!  Breast Cancer Res. 9:on line. pdf

Chapters:

    • Nguyen, D.D. and Neville, M.C. (1998)  Tight junction regulation in the mammary gland.  J. Mammary Gland Biol. Neoplasia.  3:233-246.
    • Neville, M.C., Medina, C. Monks, J. and Hovey, R.C. (1998)  Editorial Commentary:  The mammary fat pad.  J. Mammary Gland Biol. Neoplasia.  3:109-116.
    • Neville, M.C.  (1999)  Physiology of Lactation.  Clinics in Perinatology,  June.
    • Neville, M.C.   (1999)  Adaptation of maternal lipid flux to pregnancy:  Research needs.  Eur.J.Clin.Nutrition.  53:S120-S123.
    • Semba RD, Neville MC.   (1999)  Breast-feeding, mastitis, and HIV transmission: nutritional implications.    Nutr Rev. 57:146-53.
    • Monks, J.A. and Neville, M.C.   (2001) Transcytosis of proteins across the mammary epithelium into milk.  Journal of Women’s Health.  In Press 
    • Umemura, S., Morton, J. and Neville, M.C.  (2001) Lactogenesis: the transition from pregnancy to lactation.  Ped.Clin. N.A.  In Press.

Abstracts:

    • Nguyen,D.-A. and M.C. Neville (1995) Tight junction closure during lactogenesis in the mouse mammary gland. American Society for Cell Biology, Washington, D.C. 
    • M.C. Neville, V.S. Toddywalla, F.W. Kari, J. Monks, S.J.P. Gavigan (1996) Drug and protein transfer into milk: A reevaluation. Experimental Biology '96. 
    • D.-A.Nguyen and M.C. Neville. Tight junction regulation in the mouse mammary gland. International Congress of Physiology, St. Petersburg, June, 1997. 
    • D.-A.Nguyen and M. C. Neville, Tight junction regulation in the mouse mammary gland. Gordon Conference on Mammary Gland Biology, June, 1997.
    • J.Monks and M.C. Neville, A promiscuous transcytotic pathway in the lactating mouse mammary gland. Gordon Conference on Mammary Gland Biology, June, 1997. 

PubMed search (Neville MC)