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PULSe Home > Faculty Members J-L > Sophie Lelièvre
Sophie A. Lelièvre
Current Research Interests:
Research in the laboratory focuses on understanding the mechanisms by which the organization of components of the cell nucleus directs the expression and stability of the genome and how tissue architecture influences nuclear organization. To do this we use three-dimensional cultures of nonmalignant and malignant breast epithelial cells that recapitulate the formation of normal tissue structures (mammary acini) and tumor nodules, respectively. Using this system, several nuclear structural proteins, including the nuclear mitotic apparatus protein NuMA, have been demonstrated to differentially relocate upon differentiation and tumorigenesis and their specific subcellular distribution has been shown to direct gene expression and cell behavior (e.g., invasive potential, proliferation, apoptosis). We have shown that NuMA participates in chromatin organization. Our current focus is to identify the binding partners of NuMA during differentiation and tumorigenesis and decipher the nuclear mechanisms by which NuMA controls higher order chromatin structures. We have identified sequences in NuMA that are potential regulators of its function; these sequences will be used as baits for studying protein-protein and protein-DNA interactions as well as targeted subcellular localization, and for the creation of cell lines functionally altered for the protein of interest. A separate focus is to decipher the proteomic and genomic determinants of apical polarity, an important element of tissue architecture that is altered very early during breast cancer development. These determinants will be used as detection markers for the classification of breast cancer and as potential therapeutic targets. The effect of apical polarity on gene expression control is also being investigated. In addition, nanotechnology approaches, based on the use DNA tweezers, are being developed to control the expression of specific genes. These studies should yield strategies to fight against differentiation and proliferation disorders like cancers. Another emerging area of research is the development of breast cancer prevention strategies by combining epigenomics research with the study of risk and protective factors for breast tissue homeostasis. This aspect of the research is highly interdisciplinary and includes all aspects of public health necessary to develop prevention programs.
Selected Publications:
SELECTED PUBLICATIONS:
C Plachot, LS Chaboub, HA Adissu, L Wang, A Urazaev, J Sturgis, EK Asem, and SA Lelièvre. Factors necessary to produce basoapical polarity in human glandular epithelium formed in conventional and high throughput three-dimensional cell culture: Example of the breast epithelium. BMC biology (accepted for publication)
SA Lelièvre and ML Moquet-Anger. Information on breast cancer screening: Communication and Responsibilities. Revue de Droit Sanitaire et Social (Journal of Sanitary and Social Law) 06/2009, n° 3, p. 480-496
SA Lelièvre. Contributions of extracellular matrix signaling and tissue architecture to nuclear mechanisms and spatial organization of gene expression control. Special issue on Epigenetic Control of gene Expression. BBA 1790:925-935, 2009
PC Abad, B Yagci, and SA Lelièvre. Nanoprocesses in gene expression. Encyclopedia of Nanoscience and Nanotechnology (Ed. H.S. Nalwa). In Press.
G Chandramouly, PC Abad, and SA Lelièvre. The control of tissue architecture over nuclear organization is critical for epithelial cell fate. J. Cell Sci. 120:1596-606, 2007.
PC Abad, J Lewis, IS Mian, S Badve, J Xie, and SA Lelièvre. NuMA Influences Higher Order Chromatin Organization in Human Mammary Epithelium. Mol .Biol. Cell, 18:348-361, 2007.
PC Abad and SA Lelièvre. Cell nucleus nanofactory for developing anti-cancer strategies. In Cancer and Nanotechnology (Eds, H. S. Nalwa and T.J. Webster; American Scientific Publishers). Ch.14, pp1-64, 2006.
DW Knowles, D Sudar, C Bator-Kelly, MJ Bissell, and SA Lelièvre. Automated local bright feature image analysis of nuclear protein distribution identifies changes in tissue phenotype. Proc. Natl. Acad. Sci. USA. 103:4445-50, 2006.
SA Lelièvre and MJ Bissell. Three dimensional cell culture: The importance of context in regulation of function. In: Encyclopedia of Molecular Cell Biology and Molecular Medicine (EMCBMM), Vol. 11-15, 2005.
P Kaminker, C Plachot, S-H Kim, P Chung, D Crippen, OW Petersen, MJ Bissell, J Campisi and SA Lelièvre. Higher order nuclear organization in growth arrest of human mammary epithelial cells: A novel role for telomere-associated protein TIN2. J.Cell Sci. 118: 1321-30, 2005.
PC Abad, IS Mian, C Plachot, A Nelpurackal, C Bator-Kelly, and SA. Lelièvre. The C-terminus of the nuclear protein NuMA: phylogenetic distribution and structure. Protein Sci.13: 2573-2577, 2004.
C Plachot and SA Lelièvre. "DNA methylation control of tissue polarity and cellular differentiation in the mammary epithelium" Exp. Cell Res., 298: 122-32, 2004.
C Plachot and SA Lelièvre. New directions in Tumour biology: from basement membrane-directed polarity to DNA Methylation. In Mathematical Biology and Medicine Series, Cancer modeling and simulation, Chapman & Hall/CRC, 2003.
VM Weaver, SA Lelièvre, JN Lakins, MA Chrenek, J Jones, F Giancotti, Z. Werb, and MJ Bissell. Beta4-integrin-dependent formation of polarized three-dimensional architecture confers resistance to apoptosis in normal and malignant mammary epithelium. Cancer Cell, 2: 205-19, 2002.
SK Muthuswamy, D Li, SA Lelièvre, MJ Bissell, and J Brugge. ErbB2, but not ErbB1, can reinitiate proliferation and induce Luminal repopulation in growth-arrested epithelial acini. Nature Cell Biology, 3: 785-792, 2001.
SA Lelièvre, P. Pujuguet, and MJ Bissell. Cell nucleus in context. Crit. Rev. Eukar. Gene Expression, 10: 13-20, 2000.
SA Lelièvre, VM Weaver, JA Nickerson, CA Larabell, A Bhaumik, OW Petersen, and MJ Bissell. Tissue phenotype depends on reciprocal interactions between extracellular matrix and the structural organization of the nucleus Proc. Natl. Acad. Sci. (USA), 95: 14711-14716, 1998.
SA Lelièvre and MJ Bissell. Communication between the cell membrane and the nucleus: the role of protein compartmentalization 25th Anniversary Issue of J. Cell. Biochem, 30/31 suppl.: 250-263, 1998
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