Current
position
Associate Professor,
Department of Chemistry and Biochemistry,
Laurentian University
Cross-appointment,
Department of Biology, Laurentian University
Education and Training
1998-present: Associate
Professor of Biochemistry
Department of Chemistry and Biochemistry,
Laurentian University
1994-1998: Assistant
Professor of Biochemistry
Department of Chemistry and Biochemistry,
Laurentian University
1993-1994 Postdoctoral
Fellow
Canadian Red Cross Society, Quebec City
Blood Service, Division of Research and
Development, Ste-Foy (Quebec, Canada)
1988-1993 Ph.D. Molecular
and Cellular Biology
Biohormonal Regulation Laboratory, Laval
University Hospital Center, Ste-Foy (Quebec,
Canada)
1985-1988 B.Sc. Biochemistry
Université du Québec à
Trois-Rivières, Trois-Rivières
(Quebec, Canada)
Research Funding
Natural Sciences and Engineering Research
Council of Canada
Ontario Research and Development Challenge
Fund
Laurentian University Research Fund
Research
staff
Research
Investigations
Amino Acids and Cell Survival
We are interested in the molecular and cellular
events involved in the initiation, execution
and regulation of cell death in mammalian
cells. Our research program focuses on two
main facets of this problem: a more fundamental
aspect, where we investigate the intracellular
signals triggered by amino acids, and a
more applied focus, where the impact of
the modulation of cell death on the behavior
of hybridoma cells is investigated.
- Understanding
the molecular events responsible for
the induction of cell death upon deprivation
of the amino acid L-glutamine.
It has been known for the past 50 years
that L-glutamine is required for mammalian
cell survival. Not only is this amino
acid essential for the growth of most
cultured cell lines, but decreased blood
glutamine levels (resulting from catabolic
stress following severe trauma or malnourishment)
has also been shown to sensitize cells
to undergo programmed cell death, contributing
to several diseases such as sepsis,
intestinal atrophy and immunodeficiency.
Furthermore, glutamine supplementation
has been shown to improve the state
of the immune system and to prevent
some of the side effect associated with
chemo/radiotherapy. Surprisingly, the
molecular basis of glutamine-mediated
cell survival is still poorly understood.
We are using several cell models (mouse
hybridomas, intestinal epithelial cells,
neutrophils) in an effort to uncover
the molecular pathways underlying the
role of L-glutamine as a survival factor.
A major focus of our current work is
to characterize the cellular "glutamine
sensors" which link intracellular
glutamine levels to cell survival.
- Optimization
of biotechnologically-relevant mammalian
cell lines. Mammalian cell culture is
widely used to produce large amounts
of proteins of biotechnological or biomedical
interest (e.g. monoclonal antibodies).
However, cell death by apoptosis has
been shown to severely limit the productivity
of these cells, both in batch or perfusion
cultures. While the induction of apoptotic
cell death in long-term culture can
be attributed to several factors, the
exhaustion of amino acids, notably L-glutamine,
from the culture media constitutes an
important trigger. New means to improve
the viability of cultured cell lines
are therefore being sought, either by
modifying culture conditions or genetically
altering the cells themselves.
One aspect of our research program in
centered on investigating the role which
apoptosis plays in limiting the viability
of cell lines in culture. In particular,
we are exploring the molecular pathways
responsible for apoptosis in long-term
cultured cells. Our goal is to use this
newly acquired knowledge to improve
cell viability using genetic engineering
techniques (e.g. ectopic gene expression).
We are also exploring the molecular
basis of apoptosis induction in hybridoma
cells. Finally, one aspect of our research
is to determine the impact that the
gene expression profile specific to
each hybridoma cell line can have on
cell behavior and productivity.
Selected
publications
Paquette,
J. C., P.J. Guérin, and E.R. Gauthier.
(2005). Rapid induction of the intrinsic
apoptotic pathway by L-glutamine starvation.
J. Cell. Physiol. 202 (3): 912-921).
[Abstract]
Charbonneau,
J.R., T. Furtak, J. Lefebvre and E.R. Gauthier.
(2003). Bcl-xL expression interferes with
the effects of L-glutamine supplementation
on hybridoma cultures. Biotechnology and
Bioengineering. 81: 279-290.
[Pubmed]
Charbonneau,
J. and E.R. Gauthier. (2001). Protection
of hybridoma cells against apoptosis by
a loop domain-deficient Bcl-xL protein.
Cytotechnology. 37: 41-47.[Abstract]
Charbonneau,
J. and E.R. Gauthier. (2000). Prolongation
of hybridoma cell viability in stationary
batch culture by Bcl-xL expression. Cytotechnology.
34(1-2): 131-39.[Abstract]
Gauthier,
E.R., L. Piché, G. Lemieux and R.
Lemieux. (1996). Role of bcl-xL in the control
of apoptosis in murine myeloma cells. Cancer
Research. 56: 1451-1456.[Pubmed]
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