Sarah E. Millar, Ph.D. -- Dermatology Faculty

Education
1982 B.A. Cambridge University, U.K.
1987 Ph.D. University of London, U.K.

Research Area of Interest
Signaling mechanisms regulating the embryonic development and postnatal growth of skin appendages including hair follicles, teeth and mammary glands; skin and mammary gland tumorigenesis.

Research Summary
The goal of research in my laboratory is to understand how cells communicate in the skin and its derivatives. Cell-cell communication plays a critical role in the embryonic development of skin appendages such as hair follicles, teeth and mammary glands, and is also important in postnatal animals for hair growth and responses of the mammary gland to puberty, pregnancy and delivery. Abnormal intercellular communication in these organs can cause tumors as well as developmental defects. Understanding the signaling events controlling skin appendage development and growth may thus reveal novel therapeutic targets for certain tumors, as well as suggesting strategies for regeneration of hair follicles and teeth in cases of loss or absence due to disease, decay, or congenital defects.

Our current focus is the role of signaling by paracrine WNT and BMP proteins in appendage development and tumorigenesis. We have shown recently that WNT signals are required for the initiation of hair follicle and mammary gland development. These results suggest that WNT signals help to determine the fate of epidermal stem cells in the embryo. We are now using genetic mouse models, organ culture, tissue culture and microarray approaches to determine the mechanisms by which WNT signals act together with other factors to initiate the transcriptional and cellular changes associated with appendage formation.
We have also shown that BMP signaling is required for normal hair growth and has tumor suppressor activity in the skin. We are currently using transgenic and knockout mouse models to determine the mechanisms by which WNT and BMP signals control later stages of hair follicle, mammary gland and tooth development and postnatal hair growth, and are further investigating the roles played by these signaling molecules in skin and mammary gland tumorigenesis.

Skin microRNA profiling experiment
For experimental details and primary data please click here. (available on May 4th)

Dr. Millar's Lab Personnel:

Thomas Andl, Ph.D.	Research Associate
Alladin Kairo, Ph.D.	Research Associate
Yuhang Zhang, Ph.D.	Research Associate
Fei Liu, Ph.D.	Postdoctoral fellow
Monica Yunta-Gonzalez, Ph.D.	Postdoctoral fellow
Natalie Gallant	Medical Student
Brenda Watt	Graduate rotation student

Selected Publications

Reddy, S., Andl T., Bagasra, A., Lu M. M., Epstein, D. J., Morissey, E. E., Millar, S. E. (2001). Characterization of Wnt gene expression in developing and postnatal hair follicles and identification of Wnt5a as a target of Sonic hedgehog in hair follicle morphogenesis. Mechanisms of Development 107, 69-82.
Cotsarelis, G., Millar, S. E. (2001). Towards a molecular understanding of hair loss and its treatment. Trends in Molecular Medicine 7, 293-301.
Weidenfeld J., Shu W., Zhang L., Millar S. E. & Morrisey E. E. (2002). The WNT7b promoter is regulated by TTF-1, GATA6, and Foxa2 in lung epithelium. Journal of Biological Chemistry, 277, 21061-70.
Andl T., Reddy S. T., Gaddapara T., Millar S. E. (2002). WNT signals are required for the initiation of hair follicle development. Developmental Cell 2, 643-653.
Millar, S. E. (2002). Molecular mechanisms regulating hair follicle development. Journal of Investigative Dermatology 118, 216-225.
Andl, T., Ahn, K., Kairo, A., Chu, E. Y., Wine-Lee, L., Reddy, S. T., Croft, N. C., Cebra-Thomas, J. A., Metzger, D., Chambon, P., Lyons, K. M., Mishina, Y., Seykora, J. T., Crenshaw, E. B., & Millar, S. E. (2004). Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131, 2257-2268.
Reddy, S. T., Andl, T., Lu, M-M, Morrisey, E. E. & Millar, S. E. (2004). Expression of Frizzled genes in developing and postnatal hair follicles. Journal of Investigative Dermatology, 123, 275-282.
Chu, E. Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T. P., Brisken, C., Glick, A., Wysolmerski, J. J., & Millar, S. E. (2004). Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131, 4819-4829.
Lang, D., Lu, M. M., Huang, L., Engleka, K. A., Zhang, M., Chu, E. Y., Lipner, S., Skoultchi, A. Millar, S. E., Epstein, J. A. (2005). Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433, 884-7.
Devgan, V., Mammucari, C., Millar, S. E., Brisken, C., Dotto, G. P. (2005). P21^WAF1/Cip1 is a negative regulator of Wnt4 expression downstream of Notch1 activation. Genes & Development 19, 1485-95.
Shu W., Guttentag S., Wang Z., Andl T., Ballard P., Lu M. M., Piccolo S., Birchmeier W., Whitsett J. A., Millar S. E., Morrisey E. E. (2005). Wnt/beta-catenin signaling acts upstream of N-myc, BMP4, and FGF signaling to regulate proximal-distal patterning in the lung. Developmental Biology 283, 226-39.
Andl, T., Murchison, E. P., Liu, F., Zhang, Y., Yunta-Gonzalez, M., Tobias, J. W., Andl, C, D., Seykora, J. T., Hannon, G. J., Millar, S. E. (2006). The miRNA processing enzyme Dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biology, in press.

Links of Interest