Page 35 - AnnualReportGIGA2012

This is a SEO version of AnnualReportGIGA2012. Click here to view full version

« Previous Page Table of Contents Next Page »
33
Key numbers
22
Scientists
30
PhD students
8
Technicians
Laboratories
Laboratory of Functional Genetics
Stéphane Schurmans
Laboratory of Immunology and
Infectious Diseases
Michel Moutschen, Souad Rahmouni
Laboratory of Medical Chemistry
Alain Chariot, Pierre Close
Laboratory of Molecular Immunology
and Signal Transduction
Emmanuel Dejardin
Laboratory of Protein Signaling and
Interactions
Franck Dequiedt, Jean-Claude Twizere
Laboratory of Virology and Immunology
Jacques Piette
GIGA-Signal Transduction
The unit of Signal Transduction is interested in understanding how post-translational modifcations such
as phosphorylation, acetylation and polyubiquitination ultimately regulates the activation of a variety of
signaling pathways required in immunity, cell proliferation, survival, thrombosis and hemostasis. Addres-
sing how such modifcations are coordinated help to better understand why their deregulations contri-
bute to chronic infammatory and auto-immune diseases as well as to cancer. Our experimental strategies
include the characterization of mouse or zebrafsh models in which one or multiple genes of interest
are overexpressed or invalidated. Interactomic studies are also conducted in order to defne in which
pathways are acting our candidates of interest and how oncogenic viral proteins exert their functions.
More specifcally, we are exploring the mechanisms by which NF-κB-activating kinases such as NIK, TBK1
and IKKε promote cell survival when aberrantly expressed and how those candidates paradoxically trig-
ger cell death in some physiological circumstances. We also further dissect the mechanisms by which
genotoxic anti-cancer agents activates NF-κB by focusing our eforts on the modifcations of RelA/p65
by the kinase ATM. Signaling pathways relying on protein phosphatases such as VHR, LYP, SHIP-1 or SHIP-2
are also investigated to better understand how protein dephosphorylation is involved in innate immu-
nity, bacterial tolerance, lipid metabolism, cancer development and progression.
As protein acetylation is a major post-translational modifcation occurring as frequently as protein phos-
phorylation, we also focus our work on the contribution of selected acetylase and deacetylase com-
plexes in tumor initiation, angiogenesis and metastasis through the identifcation of new acetylated subs-
trates. How post-translational modifcations of some deacetylases regulate their own catalytic activity
or subcellular localization is also explored in our unit.
Assessing the C16 Ceramide-dependent post-translational modifcations of Emerin in colon cancer-
derived cell lines is also addressed to shed more lights on the mechanisms by which Ceramides promotes
autophagy and apoptosis in these cells.
Ultimately, those projects may not only defne new therapeutic targets but may also help to set up new
pharmacological tools to assess the activation status of druggable signaling pathways, such as the ones
relying on G protein-coupled receptors (GPCR) whose ligands are currently explored too.
Contact
Alain Chariot
alain.chariot@ulg.ac.be
+32 4 366 24 72
www.giga.ulg.ac.be/st