Research interests
Our main interest is to understand the molecular mechanisms by which oncogenes transform a normal cell into a cancerous one. We focus
our research on signaling pathways that are often deregulated in metabolic diseases and cancer, such as Ras/MAPK and PI3K/mTOR.
Using high-throughput proteomic approaches to identify novel effectors of the Ras/MAPK pathway
Ras/MAPK signalling is activated by most growth factors
and controls essential biological processes, including cell cycle progression, cell differentiation,
survival and motility. Activating mutations
in components of this pathway are frequently found in human
tumours, such as in pancreatic (90%), colon (50%), thyroid (45%) and
ovarian cancers (36%), as well as in melanoma (63%). We have
identified a number of novel proteins regulated by the Ras/MAPK pathway, and are
currently characterizing their roles in normal and cancer cells.
Assess the biological function of the RSK family of protein kinases
The RSK family of protein kinases contains four human isoforms
(RSK1-4). The RSK isoforms are directly
activated by the Ras/MAPK pathway, but very little is know about their roles
in cancer cells. Our group uses mouse genetics and molecular cell
biology techniques to understand the roles of these protein kinases. We have also identified
a large number of RSK substrates, which are currently being
characterized as novel effectors of the Ras/MAPK pathway.
Characterize the function and regulation of the mTOR signalling pathway
The mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that regulates cell growth as well as
organ and body size in a variety of organisms. Emerging evidence
indicates that deregulation of the mTOR pathway occurs in many
types of cancer, underscoring the importance of understanding
what lies downstream. We have identify a number of new mTOR
effectors and are currently characterizing their roles in cancer cell
growth and proliferation.
Interplay between
mechanical and biological mechanisms in cell cortex assembly
The cell cortex is a network of actin, myosin and associated
proteins that underlies the plasma membrane and determines cell shape. As such,
the cortex plays a role in normal
physiology during events involving cell deformation such as mitosis, cytokinesis, and cell locomotion, and in the pathophysiology of diseases
such as cancer. Despite its
importance, little is known about how the cortex assembles, how it is
tethered to the cell membrane, and how its mechanical properties are
regulated. The aim of this project is to uncover the molecules involved
in cortex assembly, understand their regulation, determine how cortex
mechanical properties relate to cortical ultrastructure and proteic
composition, and explore how cortical mechanics in turn influence
molecular concentrations and activities. This interdisciplinary project, in collaboration with
Guillaume Charras
(UCL),
Ewa Paluch (MPI-Dresden), and
Guillaume Romet-Lemonne (CNRS),
will enable us to rationally link proteic composition, ultrastructure,
mechanics and regulation of the cortex to one another.
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.jpg)
Normal human mammary epithelial cells
(actin filaments are stained in red, DNA in blue)
.jpg)
Breast cancer cells with hyperactivated
MAPK signalling
(as above, with the Gab2 oncogene
stained in green)

Schematic of the signal transduction
mechanisms
stimulated by hormones and growth factors
(from Roux and Topisirovic, CSHPB 2012)

Actin cytoskeleton of a blebbing
melanoma cell
viewed using an electron microscope
(image provided by Guillaume Charras) |