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Marian L. Waterman
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Position:
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Associate Professor, Microbiology & Molecular Genetics
School of Medicine
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Degree:
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PH.D., University of California, San Diego
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Research
Interests: |
Wnt signaling, cancer, gene expression; immunology; nuclear trafficking; LEF and TCF transcription factors
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Research
Abstract:
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The goal of the research program in the Waterman laboratory is to understand how a developmental signaling pathway triggered by extracellular Wnt ligands specifies changes in transcription of target genes. Dysfunctional Wnt signals can cause cancer, and it is this unfortunate aspect that continues to be the focus of our work. We have uncovered differences in the structure and activities of the LEF/TCF transcription factors that mediate Wnt signals. We have also uncovered aberrant expression and subcellular trafficking of some of these factors in cancers – particularly colon cancer and breast cancer. Two major aspects of these findings comprise our current work. First, we are studying the transcriptional and post-transcriptional mechanisms that make LEF/TCFs function non-redundantly, and we are testing whether these differences are relevant to cancer progression. Second, we are defining regulatory mechanisms at the transcriptional and translation level that cause aberrant expression of LEF-1 in cancer.
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Publications:
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Jimenez, J.J., B. L. Semler and M.L. Waterman. 2005. An internal ribosome entry site mediates translation of Lymphoid enhancer factor-1. RNA 11:1385-1399
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Atcha, F.A., J.E. Munguia., W.-H. Li, K. Hovanes, M.L. Waterman. 2003. A new b-catenin dependent activation domain in T Cell Factor. J Biol Chem 278:16169-16175
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Ishitani, T., S. Kishida, J. Hyodo, N. Oeno, J. Yasuda, M. L. Waterman, H. Shibuya, R.T. Moon, J. Ninomiya-Tsuji, and K. Matsumoto. 2003. The TAK1-NLK MAPK cascade functions in the Wnt-5a/Ca+2 pathway to antagonize Wnt/ß-catenin signaling. Mol. Cell Biol. 23:131-139
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Li, B., D.R. Mackay, Q. Dai, T.W.H. Li, M. Nair, M. Fallahi, C.P. Schonbaum, J. Fantes, M.L. Waterman, E. Fuchs, and X. Dai. 2002. The LEF1/b-catenin complex activates movo1, a mouse homolog of Drosophila ovo required for epidermal appendage differentiation. Proc. Natl. Acad. Sci U.S.A. 99:6064-9
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Holcombe, R.H., J. L. Marsh, M. L. Waterman, F. Lin, T. Milovanovic and T. Truong. 2002. Expression of Wnt ligands and Frizzled receptors in colonic mucosa and in colon carcinoma. Molecular Pathol. 55(4):220-226
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Hovanes, K.H., J.E. Munguia, T. Truong, T. Milovanovic, T.W.H. Li, J. L. Marsh, R.F. Holcombe and M.L. Waterman. 2001. Selective expression of b-catenin-sensitive forms of Lymphoid Enhancer Factor-1 in Colon Cancer. Nature Genetics 28:53-57.
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Waterman, M.L. 2001. Expression of LEF/TCFs in colon cancer. Curr. Opin. Gastroenterol. 18(1): in press.
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Hovanes, K.H., T.W.H. Li, and M.L. Waterman. 2000. The human LEF-1 gene contains a promoter preferentially active in lymphocytes and encodes multiple isoforms derived from alternative splicing. Nucleic Acids Res. 28(9):1994-2003.
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Ishitani, T., J. Ninomiya-Tsuji, S.I. Nagai, M. Nishita, M. Meneghini, N. Barker, M. Waterman, B. Bowerman, H. Clevers, H. Shibuya, and K. Matsumoto. 1999. The TAK1-NLK MAP kinase-related pathway antagonizes b-catenin-TCF signalling. Nature. 399:798-802.
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Prieve, M.P. and M.L. Waterman. 1999. Nuclear Localization and formation of b-catenin-Lymphoid Enhancer Factor-1 complexes is not sufficient for activation of gene expression. Mol. Cell. Biol. 19:4503-4515.
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Prieve, M.G., K.L. Guttridge, J. E. Munguia, and M.L. Waterman. 1998. Differential Importin-alpha Recognition of Nuclear Localization Signals within the HMG DNA binding domains of Lymphoid Enhancer Factor-1 and T Cell Factor-1. Mol. Cell. Biol. 18: 4819-4832
Ward, S.B., G. Hernandez-Hoyos, F. Chen, R. Reeves, M. Waterman and E.V. Rothenberg. 1998. Chromatin remodeling of the interleukin-2 gene: distinct alterations in the proximal versus distal enhancer regions. Nucleic Acids Res. 26:2923-34.
Porfiri, E., B. Rubinfeld, I. Albert, K. Hovanes, M. Waterman and P. Polakis. 1997. Induction of aBeta-catenin-LEF-1 Complex by WNT-1 and Transforming Mutants of Beta-catenin Oncogene 15:2833-2839.
Prieve, M., K.L. Guttridge, J.M. Munguia, and M.L. Waterman. 1996. The nuclear localization signal of lymphoid enhancer factor-1 is recognized by two differently expressed Srp-1-NLS receptor proteins. J. Biol. Chem. 271: 7654-7658.
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Address |
University of California
C135E, C154 Medeical Sciences I
Mail Code: 4025
Irvine, CA 92697
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Phone: | (949) 824-2885, 3096 |
Fax: | (949) 824-8598 |
Email: | mlwaterm@uci.edu |
URL
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www.ucihs.uci.edu/microbio/
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| Updated |
04/09/2006
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Copyright (c) Regents of the University of California, 1997. All rights reserved.
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