IMT - Institut für Molekularbiologie und Tumorforschung
AG Lauth
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Our research interests We are pursuing two major lines of research: 1) Investigating the role of tumour-stromal Hedgehog signalling in pancreatic cancer Pancreatic ductal adenocarcinoma is characterized by a high percentage of non-cancerous stromal cells which surround Hedgehog-ligand producing tumor cells. In this project, we will look into the functional role of tumor-cell secreted Hedgehog ligands on either the tumor cells themselves or on their surrounding normal stromal cells. We will focus on aspects such as tumor cell migration and formation/maintenance of cancer stem cells. In addition, we will investigate the role of Hh signaling in the activation of fibroblasts (leading to ‘stromal desmoplasia’). Furthermore, we will apply the acquired information to set up first steps of a targeted therapy for pancreatic cancer. To achieve these goals, we will make use of state-of-the-art molecular biology and cell culture methodologies as well as mouse cancer models. 2) Understanding the regulation of GLI-mediated gene transcription Several Hedgehog-dependent tumors have acquired activating alterations at the receptor level and could in future be treated by pharmaceuticals targeting these early (‘upstream’) signal transducers such as Smoothened (Figure 1). However, a growing number of tumors seem to be dependent on a ‘downstream’ activation of the Hh pathway and novel inhibitors are needed to target also these cancer forms. We have previously identified small molecule GLI antagonists (Lauth et al. (2007), PNAS 104, 8455-8460) and demonstrated the great potential of such compounds. In this project activity within the group, we will investigate mechanisms of signal transduction regulating GLI-mediated transcription. In particular, novel non-canonical regulatory processes are of interest. |
