Claudius Vincenz, Ph.D.
Research Investigator
vincenz@umich.edu

Annual Report | Biography | Research Interests  | Selected Publications 

Departmental Annual Report

2000-2001 | 1999-2000

Brief Biography

I was born in a small mountain village in Switzerland. Growing up in the countryside made it almost natural to be interested in biology. However my desire to understand everything in detail made me shift my interest away from organismal biology towards macromolecular sciences and chemistry. I therefore obtained a diploma in macromolecular sciences from the Swiss Federal Institute of Sciences in Zurich. My first American degree is a Masters from Rensselaer Polythecnic Institute in Chemistry. I obtained my Ph. D. from the University of Michigan through the Biophysics program
developing new methods to study chromatin composition. After a first post-doc at the Salk Institute studying the effect of chromatin structureon transcription I came back to Ann Arbor to join Dr. Vishva Dixit's laboratory. It is in his lab I was exposed to the molecular aspects of apoptosis. This tenure allowed me to participate in the exciting discoveries in this field from the very beginning. I continue in this field after becoming an independent investigator in the department of pathology.

Research Interests

Apoptosis, death receptors, neurodegenerative diseases, Huntington's disease, caspases, NF-kB.

The focus of the research in my lab is apoptosis. This field has made great strides during the last five years towards understanding the molecular events that are involved in this evolutionary conserved process. The pattern that has emerged is that three phases can be distinguished. A commitment phase is followed by an execution phase and the products are removed during the elimination phase.

The execution phase is characterized by the selective cleavage of key proteins by aspartic acid specific proteases named caspases. This family of proteins comprises up to date 14 members and additional members are being identified. My lab continues to clone and characterize additional caspases. Caspase 14 for example stands out because it lacks a prodomain, which keeps all other caspases in an inactive zymogen form. Caspase 14 is only expressed during development. We are currently trying to establish what the physiological function of this caspase is.

The commitment phase is not as well understood. It is during this phase that the cell integrates multiple signals that will lead to the initiation of cell death. One instance where the process is well understood is the initiation of cell death by death receptors (FAS, TNFR1, DR3, DR4). Receptor ligation leads directly to activation of caspases. Some of these receptors like TNFR1 transmit competing pro- and anti-apoptotic signals. My lab is interested in molecules that control the balance of these signals. A20 is a protein that shifts the balance in favor of protection. Surprisingly A20 also inhibits NF-kB induction, a process believed to induce anti-apoptotic genes. We are currently defining the molecular target of A20. Results indicate that it acts at the level of the signalsome. Homology searches have revealed that A20 represents a whole class of proteins conserved between Drosophila and mammals. The lab is currently cloning and characterizing these A20 homologues.

We have recently identified a Bcl-2 homologue with anti-apoptotic function. This gene, Boo, is exclusively expressed in the ovaries and we are investigating the role of the gene product in ovarian development and malignancies.

The commitment phase can involve synthesis of new pro-apoptotic genes. A good example for such a process is Glucocorticoid induced cell death in T cells. While it is well established that this is a transcriptionallly dependent process no candidate genes have been identified yet. My lab is using a combination of classical hybridization and new high-density filters to identify such genes.

Several neurodegenerative diseases have recently been recognized to be partially caused by premature apoptosis. My lab is focusing on the class of neurodegenerative diseases caused by polyglutamine expansions (Huntingtin, Ataxias). There is good evidence to suggest that these diseases induce apoptosis in specific neuronal populations by a common nuclear process. I’m investigating how this nuclear signal interfaces with the known apoptotic machinery by using in vitro and in vivo experimental systems.

Selected Publications

Weber, C. H., and Vincenz, C. (2001). A docking model of key components of the DISC complex: death domain superfamily interactions redefined. FEBS Lett 492, 171-176