Sophie
A. Lelievre,
Walther Assistant Professor of Cancer Pharmacology
DVM, Ph.D.
DVM -- University of Liege, 1990
M.A. -- University of Paris, 1991
Ph.D. -- University of Paris, 1994
Functional organization of the cell
nucleus in differentiation and cancer.
In the Lelièvre laboratory research focuses on the role of
higher order nuclear organization in the control of gene expression
and the maintenance of genome integrity. We use models of three-dimensional
culture of epithelial cells that mimic the formation of normal and
abnormal tissues and enable us to manipulate tissue differentiation.
The nuclear distribution of a number of proteins seems to reflect
different stages in the differentiation process. We are particularly
interested in the mechanisms that influence the organization of
the cell nucleus during tissue polarization, which constitutes the
latest stage during the normal process of epithelial differentiation.
Polarity is illustrated by the formation of a distinct compartmentalization
of proteins between the basal and apical poles of cells and it is
altered very early during tumor development.
The nucleus is typically located towards the basal pole of polarized
epithelial cells and certain proteins adopt a specific distribution
within the cell nucleus upon tissue polarization. Understanding
the relationship between membrane skeletal/cytoskeletal organization
and the organization of the cell nucleus in non-polarized and polarized
conditions is a critical aspect of our research endeavor. Another
important aspect of the research is to identify the genomic determinants
that control tissue polarity. By manipulating chromatin structure
we can specifically alter apical polarity. The loss of apical polarity
is not accompanied by the down regulation of known proteins that
form polarized membrane and cytoplasmic domains, but rather by a
change in their distribution, suggesting that the expression of
yet-to-be-identified genes may be responsible for higher level control
of polarity.
