Chalfant Lab


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Dr. Charles E Chalfant.


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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.