Pilot Project Awarded 2013
Christina (Voelkel-)Johnson, M.S. Ph.D.
Microbiology and Immunology
Programmed cell death or apoptosis is a mechanism crucial for elimination of aberrant cells that contribute to the development of disease such as autoimmune disorders or cancer as well as therapy resistance. Apoptotic signaling is characterized by caspase activation and nuclear disintegration, which is accompanied by altered nuclear exchange mechanisms. During apoptosis active caspase-3 is transported into the nucleus by a specific but unidentified mechanism. We found that downregulation of ceramide synthase 6 (CerS6), which preferentially generates C16-ceramides, reduces apoptotic signaling downstream of caspase-3 by inhibiting nuclear translocation of the activated enzyme. This pilot study will further study the novel link between nuclear translocation of active caspase-3 and sphingolipid metabolism.