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Xing Dai

Associate Professor, Biological Chemistry
School of Medicine

PH.D., University of Chicago

Phone: (949) 824-3101
Fax: (949) 824-2688
Email: xdai@uci.edu

University of California, Irvine
D234 Med Sci I
Mail Code: 1700
Irvine, CA 92697

Transcriptional control of epithelial differentiation in mice, stem cells, movo genes, Wnt-beta-catenin-LEF/TCF signaling
URL www.ucihs.uci.edu/biochem/faculty/dai.htm
1992 NIH Biotechnology Pre-doctoral Training Grant Award
1995 Departmental award for outstanding performance in the field of
Biochemistry and Molecular Biology at the University of Chicago
(known as the “best thesis award”)
1995 Howard Hughes Medical Institute Postdoctoral Fellow
1996 NIH Individual National Research Service Award
2001 March of Dimes Basil O'Connor Award
2004 Department of Defense Idea Award
2004 NIH Career Development Award
Appointments 1987-1989 Research Assistant, University of Hawaii, Honolulu, HI, Department of Biochemistry and Biophysics
1989-1990 Teaching Assistant, University of Chicago, IL, Dept. of Biochemistry and Molecular Biology
1989-1992 Research Assistant, University of Chicago, IL, Dept. of Molecular Genetics and Cell Biology
1992-1995 NIH pre-doctoral trainee, University of Chicago, IL, Dept. of Biochemistry and Molecular Biology
1995-1999 Postdoctoral Fellow, University of Chicago, IL, Dept. of Molecular Genetics and Cell Biology
1999-Present Assistant Professor, University of California, Irvine, Dept. of Biological Chemistry
The development, maintenance, and regeneration of complex mammalian tissues involve multi-tiered control mechanisms including those regulating commitment to different cell lineages and cellular differentiation along a particular lineage. Self-renewing tissues such as skin and testis provide excellent model systems to study the genetic pathways underlying such control mechanisms, as they contain stem cells that persist throughout the life span of an animal and possess long-term proliferation and differentiation potential. Upon receiving certain developmental and/or environmental cues, stem cells in these tissues commit to differentiation, undergo transient amplification, and subsequently cease proliferation to enter the program of terminal differentiation to produce highly specialized cells with essential biological functions. In my laboratory, we focus on the role of ovo family of genes, which encode zinc finger transcription factors and include members that have been placed downstream of the Wnt-beta-catenin-LEF/TCF and TGFbeta/BMP signaling pathways, in epithelial proliferation and differentiation. The long-term goals of my research program are to identify key upstream and downstream players in the movo (mouse ovo) -regulatory pathway, to characterize the functions of these players, and to elucidate their biochemical and genetic relationships with movo. To achieve these goals, we use a combinatory approach involving genetics, developmental biology, biochemistry, molecular biology, and cell biology. We have ongoing projects in the following areas:

1. Characterizing the cellular and molecular mechanisms of movo function in development and differentiation.
We have shown that movo1 is required for the development and differentiation of multiple tissues including skin, testis, kidney, and the urogenital tract. Our recent gene targeting studies have uncovered a role for movo2 in early embryonic development, particularly in the neuroepithelium. Using histological, cell biological, as well as gene expression analyses, we have shown that movo1 plays a role in growth suppression. Current studies focus on identifying downstream targets of movo1 and examining whether a growth inhibitory function is common to all movo genes including movo2. We do so using an array of techniques including in vitro protein-DNA interaction assays, cell culture reporter assays, primary cell cultures, and chromatin immunoprecipitation (CHIP) assays. Furthermore, we employ genetic approaches, such as creating and analyzing movo1/movo2 double mutant mice, to address any possible functional compensation/redundancy between these genes.

2. Characterizing the role of mpygo2, a newly identified core component of the Wnt-beta-catenin-LEF/TCF signaling pathway, in epithelial development and differentiation. The canonical Wnt signaling regulates ovo genes in flies and mice and has been shown to play important roles in epithelial stem cell maintenance, proliferation, differentiation, and tumorigenesis. We have cloned and characterized mpygo2, one of two pygo genes in mice that shows a broad expression spectrum consistent with the wide-spread involvement of Wnt signaling in development. Current studies focus on using genetically altered mutant mice to understand the role of mpygo2 in Wnt signaling and in normal and malignant epithelial development. We also collaborate with the Waterman lab on campus to study the role of mpygo2 in the beta-catenin-LEF/TCF transcriptional complex.
Publications Li, B. Mackay, D. R., Ma, J., and Dai, X. (2004). Cloning and developmental expression of mouse pygopus 2, a putative Wnt signaling component. Genomics 84, 398-405.
  Kaufman, C. K., Zhou, P., Pasolli, H. A., Rendl, M., Bolotin, D., Lim, K. C., Dai, X., Alegre, M. L., and Fuchs, E. (2003). GATA-3: an unexpected regulator of cell lineage determination in skin. Genes & Development 17, 2108-2122.
  Li, B., Dai, Q., Li, L., Nair, M., Mackay, D. R., and Dai, X. (2002). ovol2, a mammalian homolog of Drosophila ovo: gene structure, chromosomal mapping, and aberrant expression in blind-sterile mice. Genomics 80, 319-325.
  Li, B., Mackay, D. R., Dai, Q., Li, T. W. H., Nair, M., Fallahi, M., Schonbaum, C., Fantes, J., Mahowald, A., Waterman, M. L., Fuchs, E., and Dai, X. (2002). The LEF1/b-catenin complex activates movo1, a mouse homolog of Drosophila ovo gene required for epidermal appendage differentiation. Proc. Natl. Acad. Sci. USA 99, 6064-6069.
  Dai, X., Schonbaum, C., Degenstein, L., Bai, W., Mahowald, A., Fuchs, E. (1998). "The ovo gene required for cutcle formation and oogenesis in flies is involved in hair formation and spermatogenesis in mice". Genes & Development 12, 3452-3463.
  Dai, X. and Rothman-Denes, L. B. (1998). "Sequence and DNA strucutral determinants of N4 virion RNA polymerase-promoter recognition". Genes & Development 12, 2782-2790.
  Dai, X., Greizerstein, M., Nadas-Chinni, K., and Rothman-Denes, L. B. (1997). "Supercoil-induced extrusion of a regulatory DNA hairpin". Proc. Natl. Acad. Sci. USA 94, 2174-2179.
  Glucksmann-Kuis, M. A., Dai, X., Markiewicz, P., and Rothman-Denes, L. B. (1996). "E. coli SSB activation of N4 virion RNA polymerase: specific activation of an essential DNA hairpin required for promoter recognition". Cell 84, 147-154.
American Society for Cell Biology
Graduate Programs Cancer Biology

Cell Biology

Developmental Biology and Genetics

Mechanisms of Gene Expression

Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=4552
Last updated 04/24/2008