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Lelièvre,
Sophie A., DVM, Ph.D.
Walther Assistant Professor of Cancer Pharmacology
DVM ‘90, University of Liege, Belgium; MA ‘91,
University of Paris, France; PhD ‘94, University of
Paris
E-mail:sal@vet.purdue.edu
Research Interests:
Organization of the cell nucleus, extracellular
matrix-nucleus signaling, differentiation and tumorigenesis,
genomic instability, cellular and molecular biology. 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. To do
this we use three-dimensional cultures of non-malignant and
malignant breast epithelial cells that recapitulate the formation
of normal tissue structures (mammary alveoli) and tumor nodules,
respectively. Using this system several nuclear structural
proteins,including NuMA and telomere-associated proteins,
have been shown to relocate during differentiation and tumorigenesis
and their specific distribution has been demonstrated to selectively
direct gene expression and cell behavior. The identification
of the binding partners of these proteins in differentiated
and tumor cells and the signaling mechanisms induced by the
formation of sub-nuclear domains that include these proteins
should yield strategies to fight against differentiation and
proliferation disorders like cancers.
Publications
S. Lelièvre and MJ Bissell. “Three
dimensional cell culture: The importance of context in regulation
of function.” Encyclopedia of Molecular Cell Biology
and Molecular Medicine, in press.
P. Kaminker, C. Plachot, S. H. Kim, P.
Chung, D. Crippen, O. W. Petersen, M. J. Bissell, J. Capisi,
and S. A. Lelièvre (2005) “Higher-order nuclear
organization in growth arrest of human mammary epithelial
cells: a novel role for telomere-associated protein TIN2” J.
Cell Sci., Mar 15:118:1321-30.
Plachot C, Lelievre SA. DNA
methylation control of tissue polarity and cellular differentiation
in the mammary epithelium. Exp Cell Res. 2004 Aug 1;298(1):122-32.
Weaver VM, Lelievre S,
Lakins JN, Chrenek MA, Jones JC, Giancotti F, Werb Z, Bissell
MJ. beta4 integrin-dependent formation of polarized three-dimensional
architecture confers resistance to apoptosis in normal and
malignant mammary epithelium. Cancer Cell. 2002 Sep;2(3):205-16.
Muthuswamy SK, Li D, Lelievre S,
Bissell MJ, Brugge JS. ErbB2, but not ErbB1, reinitiates proliferation
and induces luminal repopulation in epithelial acini.
Nat Cell Biol. 2001 Sep;3(9):785-92.
De Solorzano CO, Malladi R, Lelievre
SA, Lockett SJ. Related Articles, Links
Segmentation of nuclei and cells using membrane related protein
markers.
J Microsc. 2001 Mar;201(Pt 3):404-15
Meyer-Ilse W, Hamamoto D, Nair A, Lelievre
SA, Denbeaux G, Johnson L, Pearson AL, Yager D, Legros
MA, Larabell CA. High resolution protein localization using
soft X-ray microscopy. J Microsc. 2001 Mar;201(Pt 3):395-403.
Chen, H.M., Schmeichel, K.L, Mian I.S.,
Lelièvre, S.A., Petersen, O.W., Bissell, M.J.
(2000) Azu-1: A candidate breast tumor suppressor and biomarker
for tumor progression. Mol Biol Cell 11:1357-1367.
Lelièvre, S.A.,
Pujuguet, P., and Bissell, M.J. (2000) Cell nucleus in context.
Crit. Rev. Eukar. Gene Expression, 10:13-20.
Bissell, M.J., Weaver, V.M., Lelièvre,
S.A., Wang, F., Peterson, O.W., and Schmeichel, K.L.
(1999). Tissue structure, nuclear organization and gene expression
in normal and malignant breast. Cancer Res. (SUPPL), 59:1757s-1764s.
Lelièvre, S.A.,
and Bissell, M.J. (1998). 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.
Lelièvre, S.A.,
Weaver, V.M., Nickerson, J.A., Larabell, C.A., Bhaumik, A.,
Petersen, O.W., and Bissell, M.J. (1998). Tissue phenotype
depends on reciprocal interactions between extracellular matrix
and the structural organization of the nucleus. Proc. Natl.
Acad. Sci. (USA), 95:14711-14716.
Lelièvre, S., Weaver,
V.M., Larabell, C.A., and Bissell, M.J. (1997). Extracellular
matrix and nuclear matrix interactions may regulate apoptosis
and tissue-specific gene expression: a concept whose time
has come. In Advances in Molecular and Cell Biology: Cell
Structure and Signaling, (R.H. Getzenberg, ed), JAI press
Inc., Greenwich CT, Vol 24, pp. 1-55.
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