Professor, Biological Chemistry
School of Medicine

Skin and mammary stem cells, Wnt signaling, chromatin, transcription

faculty.sites.uci.edu/xdai/

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 (generally known as the “best thesis award”)
1995 Howard Hughes Medical Institute Postdoctoral Fellowship
1996 NIH Individual National Research Service Award
2001 March of Dimes Basil O'Connor Award
2004 NIAMS/NIH Independent Scientist Award
2005 UCI Faculty Career Development Travel Award
2006,2007,2008 UCI School of Medicine Excellence in Teaching Award

1987-1989 Research Assistant, Department of Biochemistry and Biophysics, University of Hawaii, Honolulu, HI
1989-1990 Teaching Assistant, Dept. of Biochemistry and Molecular Biology, University of Chicago, IL
1989-1992 Research Assistant, Dept. of Molecular Genetics and Cell Biology, University of Chicago, IL
1992-1995 NIH pre-doctoral trainee, Dept. of Biochemistry and Molecular Biology, University of Chicago, IL
1995-1999 Postdoctoral Fellow, Dept. of Molecular Genetics and Cell Biology, Howard Hughes Medical Institute, University of Chicago, IL
1999-2006 Assistant Professor, Dept. of Biological Chemistry, University of California, Irvine,
2006-2011 Associate Professor, Dept. of Biological Chemistry, University of California, Irvine
2011- Professor, Dept. of Biological Chemistry, University of California, Irvine

My laboratory studies the chromatin/transcriptional control of mammalian epithelial development and regeneration, and how the epigenetic control mechanisms go awry during tumorigenesis. We use two closely related self-renewing epithelial tissues as our model systems, namely skin and mammary gland, to investigate the molecular control of stem cell proliferation, differentiation, and lineage plasticity. We also study how transcription factors expressed in the epidermis regulate epidermal-immune cell signaling to control skin inflammation. We employ a multidisciplinary approach combining mouse genetics with molecular characterizations.

We have shown that chromatin effector protein Pygopus 2 (Pygo2) converges with Wnt signaling to regulate multiple developmental processes including that of skin hair follicle and mammary gland. We have uncovered a critical role for Pygo2 in regulating the expansion of both normal and malignant mammary epithelial stem/progenitor cells, via "reading" and "writing" histone H3 K4 trimethylation.

We have recently identified novel roles of Ovol1 and Ovol2 transcription factors in suppressing epithelial-to-mesenchymal transition in skin and mammary epithelia, laying the ground for us to probe into an uncharted area in skin biology, namely how epithelial plasticity control mechanisms participate in regulating the fates of epithelial stem cells during tissue regeneration.

Lee B, Watanabe K, Haensel D, Sui JY, Dai X. Overexpression of Transcription Factor Ovol2 in Epidermal Progenitor Cells Results in Skin Blistering. J Invest Dermatol. 2017 Aug;137(8):1805-1808.

Haensel D, Dai X. Epithelial-to-mesenchymal transition in cutaneous wound healing: Where we are and where we are heading. Dev Dyn. 2017 Aug 10.

Dai, X. and Medzhitov, R. Inflammation: Memory beyond immunity. Nature. 2017 Oct 26;550(7677):460-461.

Lv, C., Li, F. , Li , X., Tian, Y., Zhang, Y., Sheng, X., Song, Y., Meng, Q., Yuan, S., Luan, L., Andl, T., Feng, X., Jiao, B., Xu, M., Plikus, M., Dai, X., Lengner, C., Dr. Cui, W., Ren, F., Shuai, J., Millar, S. (2017). MiR-31 promotes mammary stem cell expansion and breast tumorigenesis by suppressing Wnt signaling antagonists. Nat Commun. 2017 Oct 19;8(1):1036.

Xu, P., Dang, Y., Wang, L., Liu, X., Ren, X., Liu, M., Dai, X. *, and Ye, X.* (*co-corresponding authors). (2016). Lgr4 is crucial for skin carcinogenesis by regulating MEK/ERK and Wnt/ß-catenin signaling pathways. Cancer Letters 383: 161-70.

Hong, T., Watanabe, K., Ha-Ta, C., Villarreal-Ponce, A., Nie, Q, and Dai, X. (2015). An Ovol2-Zeb1 mutual inhibitory circuit governs bidirectional and multi-step transition between epithelial and mesenchymal states. Plos Computational Biology 11(11):e1004569.

Li, Q., Gu, B., Fang, L., Li, Y., Zhou, P., Bao, S., Huang, L., and Dai, X. (2015). Akt phosphorylates Wnt coactivator/chromatin effector Pygo2 at serine 48 to antagonize its ubiquitin/proteosome-mediated degradation. Journal of Biological Chemistry 290(35):21553-67.

Sun, P., Watanabe, K., Fallahi, M., Lee, B., Afetian, M., Rheaume, C., Wu, D., Horsley, V., and Dai, X. (2014). Pygo2 regulates beta-catenin-induced hair follicle stem cell/progenitor cell activation and skin hyperplasia. PNAS 111(28):10215-20.

Dai, X. and Medzhitov, R. Inflammation: Memory beyond immunity. Nature. Published online on October 18, 2017.

Watanabe, K., Villarreal-Ponce, A., Sun, P., Salmans, M. L., Fallahi, M., Andersen, B., and Dai, X. (2014) Mammary morphogenesis and regeneration require the inhibition of epithelial-to-mesenchymal transition by Ovol2 transcriptional repressor. Developmental Cell, 29(1):47-58.

Lee, B., Villarreal-Ponce, A., Fallahi, M., Ovadia, J., Sun, P., Yu, Q.-C., Ito, S., Sinha, S., Nie, Q., and Dai, X. (2014) Transcriptional mechanisms link epithelial plasticity to adhesion and differentiation of epidermal progenitor cells. Developmental Cell. 29(1):59-74

Gu, B., Watanabe, K., Sun, P., Fallahi, M., and Dai, X. (2013). Chromatin effector Pygo2 mediates Wnt-Notch cross-talk to suppress luminal/alveolar potential of mammary stem and basal cells. Cell Stem Cell, 13(1):48-61.

Watanabe, K., Fallahi, M., and Dai, X. (2013). Chromatin effector Pygo2 regulates mammary tumor initiation and heterogeneity in MMTV-Wnt1 mice. Oncogene. Jan 21.

Gu, B., Watanabe, K., and Dai, X. (2012) Pygo2 regulates histone gene expression and H3 K56 acetylation in human mammary epithelial cells. Cell Cycle 11(1):79-87

Gu, B., Sun, P., Yuan, Y., Moraes, R., Li, A., Teng A., Agrawal, A., Rhéaume, C., Bilanchone, B., Veltmaat J. M, Takemaru, K., Millar, S. Lee, E. Y-H. P., Lewis, M. T., Li, B., and Dai, X. (2009). Pygo2 expands mammary progenitor cells by regulating histone H3 K4 methylation. J. Cell Biology 185:811-26. (Chosen for news and commentary).

Wells, J., Lee, B., Cai, A. Q., Karapetyan, A., Lee, W. J., Rugg, E., Sinha, S., Nie, Q., Dai, X. (2009). Ovol2 suppresses cell cycling and terminal differentiation of keratinocytes by directly repressing c-Myc and Notch1. J. of Biological Chemistry 284(42):29125-35.

Nair M., Nagamori, I., Sun, P., Mishra, D., Rhéaume, C., Li, B., Sassoni-Corssi P., Dai, X. (2008). Nuclear regulator PYGO2 controls spermiogenesis and chromatin modification. Developmental Biology 320(2):446-55.

Jonckheere, N., Mayes, E.; Shih, H. P.; Li, B., Lioubinski, O., Dai., X., and Sander, M. (2008). Analysis of mPygo2 mutant mice suggests a requirement for mesenchymal Wnt signaling in pancreatic growth and differentiation. Developmental Biology, 318(2):224-35.

Nair, M. Bilanchone, V., Ortt, K., Sinha, S., and Dai, X. (2007). Ovol1 represses transcription by competing for DNA binding with the c-Myb activator and by recruiting histone deacetylases. Nucleic Acids Research 35, 1687-1697.

Qian, D., Jones, C., Rzadzinska, A., Mark, S., Zhang, X., Steel, K.P., Dai, X., and Chen, P. (2007). Wnt5a functions in planar cell polarity regulation in mice. Developmental Biology 306, 121-133.

Nair, M., Teng, A., Bilanchone, V., Agrawal, A., Li, B. and Dai, X. (2006). Ovol1 regulates the growth arrest of embryonic epidermal progenitor cells and represses c-Myc transcription. J. Cell Biology 173, 253-264.

Mackay, D. R., Hu, M., Li, B., Rhéaume, C., and Dai, X. (2006). The mouse Ovol2 gene is required for cranial neural tube development. Developmental Biology 291, 38-52.

Li, B., Nair, M., Mackay, D. R., Bilanchone, V., Hu, M., Fallahi, M., Song, H., Dai, Q., Cohen, P. E. and Dai, X. (2005). Ovol1 regulates meiotic pachytene progression during spermatogenesis by repressing Id2 expression. Development 132, 1463-1473.

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., 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.

Ogata, K., Dai, X., and Volini, M. (1989). " Bovine mitochondrial rhodanese is a phosphoprotein". J. Biol. Chem. 264, 2718-2725.

American Society for Cell Biology

Cancer Biology

Cell Biology

Developmental Biology and Genetics

Mechanisms of Gene Expression

Link to this profile
https://faculty.uci.edu/profile/?facultyId=4552

Last updated
12/07/2017