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
Development of hair follicles, mammary glands, taste papillae and teeth; regeneration and neogenesis of hair follicles and teeth; hair follicle, mammary gland and dental stem cells; skin and mammary gland tumorigenesis; microRNA functions in embryonic and postnatal skin and mammary glands.

Research Summary

Our research is focused on understanding cell-cell signaling mechanisms controlling development, stem cell function and regeneration in organs such as hair follicles, mammary glands, taste papillae and teeth that arise from embryonic ectoderm (ectodermal appendages). We have shown that Wnt/beta-catenin signaling is required for initiating the formation of hair follicles, mammary glands and taste papillae from multipotent cells in the embryonic surface ectoderm. We are using genetic gain and loss of function and microarray approaches to identify direct targets of this pathway in developing hair follicles. We are also interested in understanding the roles played by Wnt/beta-catenin signaling in regulating stem cell function, differentiation and tumorigenesis in the adult. For these studies we have developed inducible systems for expression of Dickkopf1 (a potent secreted Wnt inhibitor), deletion of the Wnt effector beta-catenin, and expression of an activated form of beta-catenin, in the epidermis and hair follicle, tooth, tongue and mammary gland epithelia in postnatal mice. We are using these mouse models to determine the effects of gain and loss of Wnt/beta-catenin signaling on hair follicle stem cells and postnatal hair growth; mammary stem cells and postnatal mammary gland development; tooth development and dental stem cells; taste papilla function; and skin and mammary gland tumorigenesis. We are also using genetic approaches to identify Wnt ligands and receptors required for appendage development, and to investigate the roles played by non-beta-catenin mediated Wnt signaling in the skin. Finally, we have shown that deletion of the miRNA processing enzyme Dicer causes major defects in hair follicle development. We are studying the functions of Dicer and miRNAs in the formation and maintenance of hair follicles and mammary glands.

Dr. Millar's Lab Personnel:

Yuhang Zhang, Ph.D.	Senior Research Investigator
Zhengquan Yu, Ph.D.	Research Associate
Yuhang Zhang, Ph.D.	Research Associate
Xinjiang Wu, Ph.D.	Post-doctoral fellow
Yeon-Sook Choi, Ph.D.	Post-doctoral fellow
Jun-Soo Yun, Ph.D.	Post-doctoral fellow
Monica Teta	Ph.D. thesis student
Matthew Leboeuf	M.D. Ph.D. thesis student
Matthew Crump	Undergraduate student

Selected Publications

Andl, T, Reddy ST, Gaddapara, T & Millar, SE (2002). WNT signals are required for the initiation of hair follicle development. Developmental Cell, 2, 643-653.
Andl T, Ahn K, Kairo A, Chu EY, Wine-Lee L, Reddy ST, Croft NJ, Cebra-Thomas JA, Metzger D, Chambon P, Lyons KM, Mishina Y, Seykora JT, Crenshaw EB 3rd, Millar SE. (2004). Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development,131, 2257-68.
Chu EY, Hens J, Andl T, Kairo A, Yamaguchi TP, Brisken C, Glick A, Wysolmerski JJ, Millar SE. (2004). Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development, 131, 4819-29.
Millar SE (2005). An ideal society? Neighbors of diverse origins interact to create and maintain complex mini-organs in the skin. PLoS Biol. 3, e372.
Lang D, Lu MM, Huang L, Engleka KA, Zhang M, Chu EY, Lipner S, Skoultchi A, Millar SE, Epstein JA (2005). Pax3 functions at a nodal point in melanocyte stem cell differentiation. Nature 433, 884-7.
Andl, T, Murchison, E P, Liu, F, Zhang, Y, Yunta-Gonzalez, M, Tobias, J W, Andl, C D, Seykora, JT, Hannon, GJ, Millar, SE (2006). The miRNA processing enzyme Dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biology 6, 1041-9.
Liu, F, Thirumangalathu, S, Gallant, NM, Yang, SH, Stoick-Cooper, CL, Reddy, ST, Andl, T, Taketo, MM, Dlugosz, AA, Moon, RT, Barlow, LA, Millar, SE (2007). Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet. 39, 106-12.
Ito M, Yang Z, Andl T, Cui C, Kim N, Millar SE, Cotsarelis G (2007). Wnt-dependent de novo hair follicle regeneration in adult mouse skin after wounding. Nature 447, 316-20.
Liu, F, Chu, EY, Watt, B, Zhang, Y, Gallant, NM, Andl, T, Yang, S, Lu, M-M, Piccolo, S, Schmidt-Ullrich, R, Taketo MM, Morrisey, EE, Atit, R, Dlugosz, AA, Millar, SE (2008). Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev. Biol. 313, 210-24.
Stark J, Andl T, Millar SE (2007). Hairy math: insights into hair-follicle spacing and orientation. Cell 128, 17-20.
Yang SH, Andl T, Grachtchouk V, Wang A, Liu J, Syu LJ, Ferris J, Wang TS, Glick AB, Millar SE, Dlugosz AA (2008). Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta3-catenin signaling. Nat Genet. 40, 1130-5.
Zhang, Y, Andl, T, Yang, SH, Teta, M, Liu, F, Seykora, JT, Tobias, JW, Piccolo, S, Schmidt-Ullrich, R, Nagy, A, Taketo, MM, Dlugosz, AA, Millar, SE (2008). Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135, 2161-72.

Links of Interest