Education/Training
- 1986-1993:
Post Doctoral training in Molecular Genetics and Genome Stability,
Fred Hutchinson
Cancer Research
Center, Seattle (USA)
- 1982-1986:
Ph.D. Mol. Biology, Université de
Lausanne
(Switzerland)
- 1978-1982:
B.Sc. Biochemistry, ETH Zurich (Switzerland)
Activities and
Honors
- Breakthrough of the
Year, Quebec Science for paper in Nature
(1998)
- Co-Founder,
Chief Scientific Officer and Member of the Board, Telogene Inc.
(2000-2006)
- Chercheur National
FRSQ (2001-2006); Canada Research Chair
Telomere Biology (2009-2023)
- Editorial
Boards: PloS ONE (2015-); eLIFE
(2017-)
- Prix d’Excellence
(Prize for Research Excellence, 25k$), CHUS Foundation;
Sherbrooke (2011).
- Prix d’Excellence
en Recherche et Innovation, (5k$); Université de
Sherbrooke (2017).
- 3rd
IJMS Award: Outstanding Contribution in Molecular Biology;
International Journal of Medical Sciences (2018)
Research
Funding
- 2013-2018 : CIHR
Operating Grant “Tracking the yeast telomerase RNA” (PI,
$151,000/yr x 5 years)
- 2017-2022 : CIHR
Operating Grant “The Yeast Telomerase RNP” (PI, $153,000/yr x 5
years)
- 2009-2023 : Research
Program support via Tier I Canada Research Chair in Telomere
Biology (PI, $200,000/yr)
- 2007-2012 : CFI
infrastructure support for scientific equipment (PI,
$6,600,000)
- 2006-2011 : CIHR Team
Grant “Platform for the study of RNA structure Function and
evolution” (co-applicant, $50,000/yr x 5 years)
Research
Interests:
Research in
the Wellinger lab is centered on questions relating to the
maintenance of the termini of eukaryotic chromosomes, the
telomeres. Telomeres are highly conserved in structure and function
amongst many eukaryotes and they are essential for genome
stability. For example, in aging humans, telomeres become
progressively degraded and the shortened telomeres have been
associated with human cellular senescence. On the other hand, in
human germinal cells there is a mechanism allowing counteracting
these losses. The mechanism is based on the enzyme telomerase which
will act and replenish the special telomeric DNA repeats. The
telomerase enzyme is composed of several protein subunits plus at
least one RNA molecule. Again, in humans, the reactivation of
telomerase during cancer development contributes an essential
property to cancer cells, namely that of a virtually endless
capacity to divide (immortality). Therefore, telomerase remains a
preferred target for the development of new anti-cancer
treatments.
Major
projects in the lab concern the interrelation of conventional
replication and cell cycle checkpoints with telomere replication.
Moreover, structure analyses of chromosome ends will reveal
insights into the molecular mechanisms at hand. Finally, we also
are at the forefront of research on structure function analyses of
the telomerase RNP.
Virtually
all this work uses Saccharomyces cerevisiae as a model
system. This organism allows us to combine biochemistry with
molecular genetics, genomics with microscopic techniques and we use
cell large scale cell culture studies as well as single molecule
tracking in vivo. Furthermore, we have developed several
new techniques to analyze telomere biology ourselves (see below on
most significant contributions).
We
collaborate with many groups in Canada and other parts of the world
(France, Germany, Israel, Great Britain, Slovakia and the USA). In
Sherbrooke, the groups of S. Abou-Elela, B. Chabot and B. Laurent
are also interested in questions relating to telomeres. We actively
collaborate with clinician-researchers on direct links between
telomere biology and human diseases, in particular hematological
cancers and acute arthritis syndromes.
Most
Significant Scientific Contributions:
- 1996:
Identification of a new step in telomere replication which
is crucial to how the field thinks about telomere maintenance and
development of techniques for telomere analysis
which are still the gold standard today, reported in Wellinger
R.J., Éthier K., Labrecque P. and Zakian V.A. (1996). Evidence for
a new step in telomere maintenance. Cell 85,
423-433 (Impact Factor = 32.3; cited >300 times) and in
Dionne I. and Wellinger R.J. (1996) Cell cycle regulated generation
of single stranded G-rich DNA in the absence of telomerase.
Proc. Natl. Acad. Sci. USA 93,
13902-13907 (Impact Factor = 12.2; cited >300
times).
- ·1998:
Identification of integral components of the telomeric capping
function. Gravel S., Larrivée M., Labrecque P. and
Wellinger R.J. (1998) Yeast Ku as a regulator of chromosomal
end-structure. Science 280, 741-744
(Impact Factor = 29.2; cited >400 times). This publication
contributed to sparking an intense interest in the field and was
the subject of numerous scientific comments and editorials: D.T.
Weave (1998) Moonlighting by DNA repair proteins, Current
Biology 8:R492; Ku – that’s an interesting protein (1998)
editorial in Trends in Genetics 14:350; D. Shor (1998)
Telomeres – unsticky ends, Science 18:1818; A. Bertuch and
V. Lundblad (1998) Telomeres and double-strand breaks: trying to
make ends meet, Trends in
Cell Biology
8:339.
- 2000-2006:
Establishment of TELOGENE INC., a privately funded biotech start-up
company, with my colleague Prof. Benoit Chabot. From
2000-2006, I served as Executive VP Research and Chief Financial
Officer. I was responsible for carrying out the company’s research
projects and for negotiating IP licensing agreements with our
partners and investors. I also served as Telogene’s Chief
Scientific Officer and chaired the company’s Scientific Advisory
Board. In 2006, GeminX Inc. acquired Telogene and its technology.
GeminX continues to develop the technology to this day.
- 2006: We were the
first to connect telomere replication to the cell cycle
machinery, uncovering an entirely new side to telomere
biology, in Vodenicharov M.D. and Wellinger R.J. (2006)
DNA-degradation at unprotected telomeres in yeast is regulated by
the CDK1 (CDC28/Clb) cell cycle kinase. Molecular
Cell 24, 127-137 (Impact Factor = 13.5; cited >100
times). Several editorials were published on this seminal report,
including those by Teixeira and Gilson (2006) Mol Cell
24:491; and Ferreira (2007) Nat Cell Biol
9:22.
- 2011: We were the
first to track individual telomerase RNPs in living cells in real
time, overturning major dogmas in the field whilst
reconciling a series of apparently conflicting reports previously
published in leading journals such as Science, Nature and
Cell. Our breakthrough publication, Gallardo F., Laterreur
N., Querido E., Wellinger R.J.* and *P. Chartrand (*Co-PIs)
(2011). Live cell imaging of cell cycle dependent
telomerase RNA dynamics. Molecular Cell
44(5):819-827 (Impact Factor = 12.5; cited >50 times),
was the subject of a commissioned accompanying Preview by Hocine S.
and R.H. Singer (2011) Mol Cell 44:685-686. Our report was
also the most frequently downloaded Molecular Cell paper
from December 2011 to January 2012.
- 2016: We discovered
new telomerase components, even though many labs were
seeking them for years. This breakthrough links telomerase with
other RNPs and reshapes research on telomerase, See: Lemieux B.,
Laterreur N., Wellinger R.J. (2016). Yeast telomerase shares
subunits with ribonucleoproteins RNase P and RNase MRP.
Cell 165(5): 1171-1181. (IF 29.0)