AG Radeke

Figure 1. Projects of the group are centered around the role of dendritic and T cells in chronic inflammation and cancerogenesis (click on project items for details).

Introduction

Infiltrates of mononuclear cells represent the hallmark of chronic inflammation. Following tissue injury cells of the innate and adaptive immune system invade the respective tissue through their interaction with adhesion molecules and chemotactic factors, such as bacterial components, lipids, complement fragments and chemokines. Different from acute inflammation, chronic inflammation is specifically characterized by repetitive and non-healing injury based on genetic, environmental immune deviating predisposition, and by pathological homing of immune cells finally leading to tertiary lymphoid structures as major drivers of chronicity. The interaction of the injurious agent and local cells with the professional immune system will have a decisive influence on the transition from acute to chronic inflammation, a process finally destroying vital organ function. Chronic inflammatory processes always include futile repair processes including cell protective mechanisms that eventually will support a cancerogenic transformation. Our research interest focuses on different aspects of chronicity and carcinogenesis in relevant diseases models and affected patients and the evaluation of pharmacological targets.

Current topics

(1) Dichotomy of inflammation-associated carcinogenesis in colitis

A major discussion is going on about the dichotomy of carcinogenesis either evolving from inflammation-induced cancer or cancer-induced pro-tumor inflammation. In different projects we try to elucidate the nature of inflammation-induced carcinogenesis which can be e.g. based on a pro-tumorigenic Th2 driven inflammation or pathological crypt remodelling in the course of chronic inflammation. On the other hand, emerging tumors are able to escape the immune system or even modulate it for their own advantage. We have found, that sphingolipids, especially S1P lyase are major contributers to this dichotomy. With the help of e.g. CRISPR/Cas9 we modulate the sphingolipid-axis in hematopoietic cells or colon tissue cells and investigate the impact on disease etiology, crypt remodelling or metastasis. Furthermore, we hypothesize that the dual roles of anticarcinogenic and immunomodulatory natural products formulated in nanoemulsions may supplement cancer immune therapy.

Figure 2. Chronic inflammation may drive carcinogenesis and cancer may provoke inflammation. Within this project we try to understand modulators of both and define therapeutic targets

(2) Pathogenesis of Systemic Sclerosis – involvement of sphingolipid signaling

Systemic Sclerosis (SSc) is a clinically heterogeneous autoimmune and connective tissue disease affecting the skin and several inner organs. Its pathophysiology is mainly characterized by microangiopathies, inflammation and fibrosis. This project