Victor C. K. Yu spent one year in Neurex Corporation as a staff scientist before joining the Howard Hughes Medical Institute at the University of California, San Diego, as a Leukemia Society of America fellow. He joined the IMCB in 1993 and is now an Associate Professor.

1. Mechanism Of Apoptosis In Mammalian Cells

   Programmed Cell Death: Suicide Machine for the Ultimate Sacrifice
   
   When a cell in our body becomes severely damaged to the point that it could be harmful to the neighboring cells, the cell commits suicide. Recent evidence suggests that improper functioning of the cell suicide program is a major contributing factor to many human diseases

Schematic illustration of representative signaling pathways of apoptosis in mammalian cells

Apoptosis, or programmed cell death, is the process by which a cell actively commits suicide using tightly controlled mechanisms. It occurs through the activation of a cell-intrinsic suicide program. The basic core machinery necessary to carry out apoptosis appears to be present in essentially all cells at all times. However, activation of the suicide program is highly regulated and under the tight control of a network of interrelated signals to ensure the proper functioning of this important physiological process. It is believed that the malfunction of this signaling system is one of the important causes of some human diseases, including cancer (insufficient cell death) and Alzheimer’s disease (excessive cell death). Dr. Yu’s lab is investigating the function and regulation of the apoptotic signaling processes in mammalian cells. They studied the signaling and regulatory mechanisms that control the apoptotic function of the tumor suppresser protein, p53, in human neuroblastoma (one of the most common forms of childhood cancer) and discovered that the translocation defect of p53 in these cells could be restored by a small molecular weight compound known as H-7 (1-(5-isoquinolinesulfonyl)-2-methylpiperazine). Because H-7 appears to kill neuroblastoma cells through the p53-dependent pathway, the H7-neuroblastoma cell model system thus becomes a powerful tool to permit the identification and understanding of the molecular steps involved in p53-mediated apoptosis. To facilitate the identification of the additional signaling components that are involved in apoptosis, they have also employed a protein-protein interaction cloning strategy to identify genes that encode proteins that can specifically associate with some of the key molecules in the death signaling pathway. Emphasis has been placed on identifying genes that play important roles in mediating cell death in the brain. Currently, several novel genes, including a gene that is expressed exclusively in the brain, have been identified and their functions in apoptosis signaling are being actively studied in Dr. Yu’s laboratory. Novel therapeutic approaches can be devised by identifying important molecules that participate in the signaling events in apoptosis and by gaining an understanding of how these molecules are being regulated.