The research division Preclinical Research is divided into the departments Preclinical Research at the Frankfurt am Main site, Preclinical Research with a focus on the blood-brain barrier at the Göttingen site and Preclinical Research with a focus on mast cell-mediated diseases at the Berlin site.
Peclinical Research – Frankfurt am Main
State-of-the art technologies are utilized for molecular and cellular investigations on gene expression and modulation, cell signaling, mediator generation and cell surface receptor function, particularly in relation to immune responses. Novel assays are established and used to characterize and validate novel molecular targets and modulators of targets (drugs) in vitro, ex vivo and in vivo. Models for the simulation of inflammatory, immune-mediated, neuro-inflammatory and -degenerative diseases together with specific analytical evaluation methods are developed using specific outcome measures, including bioimaging, which facilitate translation to the patient. In addition, and together with the drug discovery unit, we are able to develop novel small molecules, biologics and peptides for therapeutic approaches, as well as diagnostic biomarkers.
In vivo Pharmacology
Established and predictive animal models are available which cover a range of inflammatory, autoimmune, pain and neurodegenerative indications. Variables determined include direct functional, imaging and behavioral analyses, as well as ex vivo analyses of immunohistological, immunological, cellular (e.g. FACS) processes and receptors, mediators, enzymes, as well as signaling, proteomic and genomic processes. In addition to the pharmacodynamics investigations, pharmacokinetic experiments are also performed.
In vitro Pharmacology
(Head: Dr. Susanne Schiffmann)
A considerable number of innovative in vitro tests are available to investigate the effect of new targets or drugs in physiological or pathophysiological processes. Emphasis is laid on cellular signaling processes, lipid metabolism, neuronal cell responses and immune cell activities. Beneath the indication-specific assays, also cytotoxicity, proliferation, cell cycle, apoptosis, and second messenger assays can be performed. Primary cells from donors or patients are used in the in vitro test systems for best prediction of the human disease situation. In addition, the analysis of “adverse outcome pathways” has been implemented. Furthermore, in vitro models for analysis of bioavailability of drug candidates and chemicals/pigments are established, e.g. cell barrier or stability assays.
Molecular Biomarkers and Immunotherapeutics
(Head: Dr. Nicole Ziegler)
In complex diseases such as immuno-mediated inflammatory diseases, the causes are often unknown and the clinical manifestations are heterogeneous. Therefore, research is performed to investigate molecules which are helpful for the risk assessment regarding disease onset, earlier and more accurate diagnosis as well as prognosis. These molecular biomarkers support the development of new therapies. They are applied in clinical trials for patient selection and for receiving beneficial information relating to the efficacy and safety of the tested drugs. In addition, by analyzing molecular biomarkers new pathomechanisms and mode of actions are revealed. State-of-the-art molecular biology techniques (next-generation sequencing, proximity extension assay) are applied to discover genetic, epigenetic and protein-based biomarkers.
There is a high unmet need for further and more effective treatments of immune-mediated diseases. Therefore, the group supports the discovery of novel, innovative therapeutic approaches.
(Head: Prof. Dr. Andreas von Knethen)
Most important for this working group is the further development of translational models and retranslational approaches for target and drug discovery and validation in suitable test systems in critical care indications. For example, telemetric in vivo methods are used for the continuous registration of (patho-)physiological processes to monitor the acute progression of lung and kidney injuries as well as disorders of the coagulation and immune system for tailored therapeutic interventions, similar to the intensive care unit. Furthermore, retranslational OMIC-technologies are implemented for better characterization of changes of the immune system, e.g. in patients with COVID-19.
(Head: Prof. Dr. Klaus Scholich)
Around 5 million people in Germany suffer from neuropathic pain, which develops after damage of neurons of the peripheral or central nervous system. These forms of pain are very heterogeneous and are currently difficult to treat, since the available drugs are not very effective or patients suffer from significant side effects. Therefore the group focuses on the development of drugs with the goal to treat painful neuropathies in patients. Current projects include the identification and validation of new targets for chemotherapy-, tumor-, trauma-, and diabetes-induced painful neuropathies. Here, the focus is on the analysis of endogenous signaling mediators and their role in the development of acute and chronic neuropathies employing animal as well as cellular models. In cooperation with other groups within Fraunhofer ITMP, new compounds are developed from high-throughput screening and medicinal chemistry to clinical studies.
Peclinical Research with focus on Blood-Brain-Barrier - Göttingen
Preclinal research with focus on mast cell-mediated diseases - Berlin
(Head: Prof. Dr. Martin Metz, Berlin)
The aim of our research is the optimal care of patients with mast cell-mediated diseases and their differential diagnoses (e. g. urticaria, angioedema, mastocytosis, chronic pruritus, autoinflammatory diseases). For this purpose, we identify and characterize biomarkers and predictors in blood, interstitial fluid, or skin tissue using state-of-the-art OMICS technologies for reliable diagnosis, disease progression, and prediction of the effectiveness of personalized therapies. In addition, we develop and validate devices and instruments to improve clinical diagnostics, and to make diseases "investigable" within the framework of controlled clinical studies using validated devices and questionnaires, thus enabling the development of drugs for these diseases. We test the mechanisms of action of current and future therapies in various preclinical in vitro, ex vivo and in vivo models. For this purpose, in addition to extensive laboratory equipment, we have numerous investigation methods for use in humans, such as laser speckle photometry, volumetry, thermography, planimetric morphometry and devices for skin physiological measurements such as pH, pigmentation and skin redness as well as transepidermal water loss.