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Research
Interests
My major research interest is the
investigation of defects in chromosome segregation producing aneuploidy in
mitotic cells. To this aim, I have mainly used molecular cytogenetic and cell
biology approaches.
In the past, I have developed in situ hybridization approaches that allowed
the discrimination between aneuploidy and other types of cell damage, as well
as the identification of cellular mechanisms inducing aneuploidy. My
expertise in fluorescence in situ hybridization offered me the opportunity to
collaborate with groups working in several different fields, such as
epidemiology, toxicology, molecular biology, and gene therapy.
In the effort to identify aneuploidy-inducing cellular mechanisms in mitotic
cells I have recently focused on the study of lagging chromosomes, which are
chromosomes that do not migrate to the spindle poles during anaphase, but lag
behind at the cell equator. These chromosomes can induce aneuploidy in 50% of
the cases, depending on where cytokinesis occurs at the end of mitosis. I
showed that merotelic kinetochore orientation (a single kinetochore attached
to microtubules coming from both spindle poles) is responsible for lagging
chromosomes, which cannot migrate during anaphase because they are pulled by
forces directed in opposite directions. A cell cycle control mechanism, the
mitotic checkpoint, prevents anaphase onset in the presence of unattached
kinetochores or lack of tension between sister kinetochores, and provides
time for correction in cells with mis-attached chromosomes. Surprisingly,
merotelic kinetochore orientation does not activate the mitotic checkpoint,
and this, combined with its potential in inducing aneuploidy, makes it a
particularly interesting mitotic defects. However, despite the fact that the
mitotic checkpoint is not activated, I have recently found that merotelic
kinetochore orientation occurs very frequently in early mitosis in mammalian
tissue cells and error correction is achieved by two different mechanisms.
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