We are principally a laboratory dedicated to the
study of bioactive lipid molecules. Our main areas of
research are;
-
Ceramide regulation of the alternative splicing of Bcl-X pre-mRNA
- The
role of ceramide kinase and ceramide-1-phosphate in eicsosanoid
synthesis
- The role of the alternative splicing of
caspase 9 in oncogenesis
Traditionally the role of lipids were
thought to be one of maintaining membrane structure and
acting as a source of fuel for the cell. It is in the recent
past that the importance of lipids as signaling molecules
has started to emerge. One group of lipids, namely, sphingolipids have been gaining increasing attention
in this regard. This group of lipids include ceramide,
ceramide-1-phosphate (C1P), sphingosine,
sphingosine-1-phosphate (S1P).These four lipids have been implicated in a diverse number of
signaling processes that regulate inflammation, cancer,
apoptosis, etc.
Our lab was the first to identify the
role played by Ceramide-1-Phosphate (C1P) in the induction
of the inflammatory cascade. C1P was shown to activate cPLA2,
the enzyme responsible for catalyzing the first rate
determining step in the production of inflammatory
mediators. We have shown this process to occur through a
direct binding of C1P to cPLA2 that result in
decrease in the calcium requirement of cPLA2.
More information on this project can be found in the
Research section
We have also identified a role for the
action of ceramide in the alternative spicing of Bcl-X pre
mRNA. The relative ratio of Bcl-X small and large isoforms (Bcl-X(s)
and Bcl-X(L) respectively) determine the
outcome of apoptotic stimuli. Bcl-X(L) is anti
apoptotic while Bcl-X(S) is pro apoptotic. We
have identified that one of the mechanisms of induction of
apoptosis by ceramide is through the regulation of the the
alternative splicing of Bcl-X pre mRNA. For further
information on this project refer to
Research
Our laboratory has also
demonstrated that SRp30a is a required RNA splicing factor for
both basal and ceramide-induced expression of caspase 9a via regulation
of exon inclusion. We now
are examining the role of this mechanism in oncogenesis and sensitivity of
cells to various chemotherapies. Further information on this project can
be found under Research.
