Research Abstract:
Research in my laboratory is divided between studying hair follicle and female reproductive tract development. Using both systems, we are interested in studying how homeobox genes control epithelial differentiation. Mice deficient for the Msx2 homeodomain protein exhibit cyclic alopecia providing a unique model to study the molecular mechanisms of hair differentiation and hair loss. Many signaling pathways are active during hair differentiation and hair cycling. Integrating Msx genes into the existing pathway constitutes a major focus of the laboratory. We have shown in the hair cortex, Msx2 functions in a genetic pathway involving Bmp4 and Foxn1. Msx2 and Foxn1 also impinge on the Notch signal pathway during cell-fate decision in the hair bulb. Currently we are trying to identify direct Msx2 targets in the hair follicle, which may shed light on the molecular mechanism of alopecia.
In addition to our interest in hair biology, the lab is also interested in transcription factors regulating uterine epithelial differentiation. One approach to uncover genes that are important for uterine development is to identify genes whose expression is altered en route to abnormal uterine differentiation. Proper uterine cytodifferentiation can be disturbed by developmental exposure to a synthetic estrogen diethylstilbestrol, a known teratogen for the developing reproductive tracts. Using a combination of microarray technology and in situ hybridization, we have identified an array of transcription factors whose interesting expression profiles suggest an important role in regulating uterine cytodifferentiation. Currently we are using transgenic and knockout technologies to test their in vivo function.
Selected Publications:
Liu, L, Lee S, Zhang J, Peters SB, Zhang Y, Yin Y, Koff A, Ma L, Zhou P.CUL4A abrogation augments DNA damage response and protection against skin carcinogenesis. Molecular Cell 2009 34: 451–460.
Cai J, Lee J, Kopan R, Ma L. Genetic interplays between Msx2 and Foxn1 are required for Notch1 expression and hair shaft differentiation. Developmental Biology 2009 326: 420-430.
Ma L. Endocrine disruptors in female reproductive tract development and carcinogenesis. Trends Endocrinol Metab. 2009 (In Press).
Lin C, Yin Y, Long F, Ma L. Tissue-specific Requirements of b-Catenin in External Genitalia Development. Development 2008 135: 2815-2825.
Yin Y, Huang WW, Lin C, Chen H, MacKenzie A, Ma L. Estrogen suppresses uterine epithelial apoptosis by inducing Birc1 expression. Molecular Endocrinology 2008 22: 113-125.
Last Updated: 08/19/2009 |