News and Events BMDCR
Dr. Marcus Peter received the Walter and Christine Richtzenhain Prize for Experimental Cancer Research
On May 5, 2000, in Heidelberg, Germany, Marcus Peter, Ph.D.
(shown at right), Associate Professor in the Ben May Department for
Cancer Research, received the Walther and Christine Richtzenhain Prize
for Experimental Cancer Research from Prof. Harald zur Hausen, Director
of the German Cancer Research Center.
The Richtzenhain Prize is given every other year to a scientist under the age of 40 who has done outstanding research in experimental Cancer Biology in a German institution. Dr. Peter received his $10,000 prize for his work elucidating the signaling pathways in apoptosis at the Heidelberg Cancer Center prior to his recruitment to the Ben May Department for Cancer Research in 1999.
Dr. Peter is already an acknowledged leader in the field of apoptosis (or programmed cell death) research. His work on the signaling pathways involved in the cell death process has been novel and noted to be of highest scientific quality. Nearly 5 years ago, using classical immunoprecipitation protocols in combination with high-resolution 2D gels, Dr. Peter;s research group in Heidelberg reported identification of a number of proteins (CAP1-4) that associated in a ligand dependent fashion with the death domain (DD) of CD95. Together with the receptor these proteins formed what they termed the death-inducing signaling complex (DISC). The first identified component of the DISC (CAP-1, 2) was the DD containing adapter protein FADD/Mort1. At its N-terminus FADD contains a cytotoxic region that was called the death effector domain (DED). The essential protein of the DISC (CAP4) required the FADD DED for recruitment to the DISC. Together with Dr. Matthias Mann's group at the EMBL in Heidelberg (Germany) and Dr. Vishva Dixit's lab (Ann Arbor, Michigan), Dr. Peter's group succeeded in cloning this critical DISC component by employing. new sequencing and cloning techniques. CAP4 turned out to be a receptor coupled caspase. Since this enzyme contained two DED at its N-terminus, we called it FLICE (for FADD-like ICE). It is now known as caspase-8. Two different splice forms (caspase-8/a and 8/b) are being recruited and thereby activated by the DISC. The active caspase-8 subunits are then released and can cleave various intracellular substrates among which are likely other caspases such as caspase-3 and components of the intermediate filament system. The cloning of caspase-8 allowed for the first time to link two levels of the apoptosis signaling pathway: the level of the death receptors with the level of the caspases. The importance of this finding was acknowledged among others by Science, which selected the cloning of caspase-8 to be among the ten most important discoveries in all natural sciences in 1996.
Dr. Peter has brought to the BMDCR his considerable scientific talent and a conviction that significant advances in basic cancer research lead to therapeutic advances. He remains convinced that the rapidly increasing knowledge on apoptosis signaling pathways on the molecular level, especially of the death receptors, will eventually answer some of the fundamental questions in Immunology, Cancer Biology, and Medicine, namely the question how infected cells (by pathogens such as viruses, bacteria or intracellular parasites) or cancer cells manage to escape detection and/or destruction by the immune system. By regulating apoptosis resistance of these cells, therapies can be designed and applied.
In addition, an increasing number of diseases are characterized by a dysregulated rate of apoptosis mediated by death receptors. The discoveries of caspase-8 and the physiological apoptosis regulator c-FLIP now provide the basis to better understand many of these diseases on the molecular level. In addition, the identification of the two apoptosis signaling pathways may have great implications for therapeutic approaches that are based on interfering with apoptosis regulation.