Department / Division:
Pediatrics
/
Blood and Marrow Transplantation
Address:
DUMC 3350
Durham, NC 27710
Appointment Telephone:
(919) 668-1100
Office Telephone:
(919) 668-1120
Fax Telephone:
(919) 668-1180
Clinical Interests:
Pediatric bone marrow transplant, oncology, new treatments in high risk
neuroblastoma, research-chemotherapy induced apoptosis
Research Interests:
Dr. Driscoll's experiments suggest that simple over-expression of acid sphingomyelinase is not sufficient for the induction of cellular death, but indicate other sites of regulation. The fact that ceramide, the product of sphingomyelinase activity did not accumulate despite a 6.5 fold increase of enzyme activity as measured in cellular homogenates suggests the existence of additional mechanisms for controlling intracellular ceramide level. Acid sphingomyelinase regulation occurs at gene transcription as demonstrated by northern analysis. Additional regulatory sites may be at the enzyme itself by sphingomyelinase activating proteins and/or changes in ceramide metabolism. The changes in ceramide metabolism could involve ceramidases, sphingomyelin synthetases, or the synthetic enzymes of complex sphingolipids. The conclusions from this data are that over-expression of acid sphingomyelinase is not sufficient to induce cell death or ceramide accumulation, but imply that acid sphingomyelinase activity and intracellular ceramide are regulated at several sites.
