Apoptosis

Apoptosis or programmed cell death is the most common form of cell death in eukaryotic organisms. A faulty regulation of apoptosis can cause human diseases. For example, there is too much apoptosis in HIV infections, in tissue damage by physical or chemical stress or in neurodegenerative diseases. By comparison, too little apoptosis is involved in the formation and progression of cancer. Although our understanding of the basic mechanisms of apoptosis has rapidly grown in the last years, the translation of this new knowledge into clinically relevant, pathophysiological concepts is only progressing slowly.

The clinical research group “Regulation of Apoptosis and its Dysfunction in human Diseases” bundles clinically oriented research activities in the field of apoptosis with the perspective to transfer new findings of basic research into clinical practice. In six sub-projects, cell death signalling pathways in human diseases are examined that are characterised either by a deficiency in apoptosis (cancer) or by an excess in apoptosis (AIDS, neurodegenerative diseases). The clinical research group is a continuation of the long-standing research interest of our department at Ulm University that was funded from 2003 to 2005 as "Landesforschungsschwerpunkt Apoptose" by the state of Baden-Württemberg. The clinical research group is expected to strengthen the research profile of the Medical Faculty at Ulm University.

As shown in the illustration, the cross-project research question is, in which manner pathogenic stimuli like DNA damage (P1-5), death receptor ligands (P4, P5), viral proteins (P6) or pathological protein aggregates (P5) lead to a dysfunction of apoptosis signaling pathways and therefore to an excess or a deficiency of apoptosis, causing human diseases (pathologically increased apoptosis in HIV infection (P6) or neurodegenerative diseases (P5); pathologically reduced apoptosis in cancer (P1-4, 7).

Uncovering the molecular mechanisms which are responsible for the dysfunction of apoptosis in the human diseases investigated will provide the basis for the development of new diagnostic and therapeutic strategies for modulation of apoptosis and for their evaluation in preclinical disease models and with primary material from patients.

Therefore, there is a long-term perspective to transfer the new knowledge on the molecular pathogenesis of human diseases gathered in the clinical research group, namely on the dysfunction of apoptosis signaling pathways, into clinical practice („from bench to bedside“).

illustration: the role of apoptosis signaling pathways in human diseases