Signalling Networks in the Hematopoetic System and Oncology

Co-ordinators: PD Dr. S. Fulda, Prof. Dr. Th. Wirth

Cancer constitutes one of the most common causes of death in Western countries. The aggressive cancer cell phenotype is the result of a variety of genetic and epigenetic alterations leading to deregulation of intracellular signaling pathways. Such alterations include deficiencies of the cancer cell to undergo apoptosis, a cellular suicide program critical for tissue homeostasis. Tissue homeostasis critically depends on a balance between cell proliferation and cell death. Defects in signaling networks regulating apoptosis underpin both tumorigenesis and drug resistance, and because of these defects cancer therapy often fails. Thus, understanding the molecular events that regulate such fundamental cellular programs in normal and malignant cells provides a paradigm to explain the relationship between cancer genetics and treatment sensitivity and should enable a more rational approach to cancer diagnosis, drug design and therapy.

University of Ulm has had a longstanding tradition in the field of oncology and hematology. Mainstays of the current existing structure are clinical departments and other departments/divisions within the Faculties dedicated to this research field as well as core facilities. The University Hospital of Ulm has the privilege to harbor one of the largest units for Hematology in Germany, both for adult and pediatric patients, including two large hematopoietic stem cell transplantation units. Established core facilities include a Clinical Trials Unit and facilities for tissue banking, high-throughput mutation screening, FACS sorting, microarray-based studies and for the generation of transgenic or knockout mutant mice. This tradition is also reflected by several DFG-funded research centers dedicated to the topic of oncology and haematology, including the collaborative research center SFB 518 “Inflammation, regeneration and transformation of the pancreas”, the clinical research unit KFO120 “Selective internal radiotherapy” and the scientific focal point “Deregulation of apoptosis as cause for disease”.

This reseach training group is characterized by an interdisciplinary and also intersectorial composition. Principles investigators involved in teaching are members of the Medical Faculty, the Faculty for Natural Sciences, the Faculty of Computer Sciences and the Institute for Laser Technology in Medicine and Measuring Engineering. In addition, many cooperations between academic teams and industrial partners provide a solid basis for intersectorial transfer of knowledge and innovation. The main research topics of this research training group comprise signal pathways in normal and malignant hematopoiesis, control of apoptosis in normal and malignant hemato-lymphopoiesis, functional genomics, epigenetics and epigenetic therapy, DNA repair, protein kinases, photonics. This research training group started in October 2006.

Project S. Fulda, University Children's Hospital, Molecular Oncology:
Role of „Inhibitor of Apoptosis Proteins“ (IAPs) in normal and malignant hematopoiesis

Project S. Fulda, University Children's Hospital, Molecular Oncology:
Regulation of apoptosis and differentiation by sonic hedgehog

Project U. Knippschild, Institute General-, Visceral-, and Transplantation Surgery
CK1 signalling and apoptosis

Project T. Seufferlein, Institute of Internal Medicine I
Mechanisms of  keratin-reorganization by bioactive lipids and their role in defining cellular mechanics, adhesion, migration and metastasis of pancreatic cancer cells