Research Areas

Within the current funding period, NeuroCure research topics focus on cerebrovascular diseases, neuroinflammation and disorders of functional network structures, with special interest on typical neurological diseases such as stroke, multiple sclerosis, epilepsy and other developmental disorders of the central nervous system (CNS). The research topics are investigated in seven research areas (A-G). Consistent with our translational research approach, a basic scientist and a clinical researcher jointly coordinate each research area.
 
Research area A ⁞ Mechanisms of damage

Coordinators: Endres and Kloetzel

Principal Investigators: Dirnagl, Geiger, Heinemann, Heppner, Kettenmann, Kühn, Meisel, Paul, Priller, Schroeder, Schülke-Gerstenfeld, Vajkoczy, Villringer, Wanker

Protecting brain tissue against destruction is one of the key challenges in acute and chronic neurodegenerative diseases. New findings show that a significant overlap exists between cell death mechanisms of clearly different brain diseases. Our research focuses e.g. on aberrant cell cycle activity, epigenetic mechanisms, the ubiquitin-proteasome system and protein misfolding, protein-protein interaction networks. Thus, understanding and consequently interrupting the damage cascade in diseases of the CNS is a main goal, which we pursue from preclinical models to clinical trials.

 

Research area B ⁞ Endogenous neuroprotection

Coordinators: Dirnagl and Flöel

Principal Investigators: Endres, Heinz, Heppner, Kettenmann, Meisel, Priller, Vajkoczy

Understanding endogenous brain protection and exploiting the underlying signaling pathways for therapeutic purposes is our joint aim in order to develop innovative forms of treatment for stroke, multiple sclerosis and epilepsy. Our strategies involve, among others, the protective effects of HIF-1 and erythropoietine, preconditioning through upregulation of endothelial nitric oxide synthase, protective effects of multi-drug-transporters in disturbances of blood-brain barrier function, and epigenetic modulation. These innovative therapeutic approaches to utilizing endogenous repair mechanisms may soon also be of clinical value to stroke patients and patients with other brain disorders.

 

Research area C ⁞ Regeneration

Coordinators: Eickholt and Priller

Principal Investigators: Birchmeier, Dirnagl, Endres, Esplugues, Flöel, Heppner, Kettenmann, Lehnardt, Meisel, Scharff, Vajkoczy, Villringer, Wanker

We have set the long-term goal of investigating and restoring neurological function after injury or disease. For this, dysfunctional or lost neurons and myelin sheaths must be replaced, nerve fiber regeneration stimulated and plasticity promoted. To this end, the research groups are using the therapeutic potential of adult bone marrow and CNS stem cells, as well as stem cell-based methods of gene therapy. In addition, we are working on stimulating axon regeneration and synaptogenesis to replace degenerated fibers after insult. The hope is to be able to improve brain repair by better understanding and exploiting the complex interactions between the nervous, immune and hemoangiopoetic systems following CNS injury or disease.

 

Research area D ⁞ Crosstalk between nervous and immune system

Coordinators: Heppner and Meisel

Principal Investigators: Dirnagl, Esplugues, Kettenmann, Kloetzel, Lehnardt, Paul, Priller, Radbruch, Vajkoczy

In classical inflammatory disorders of the nervous system such as multiple sclerosis but also in primarily non-inflammatory injuries such as stroke and epilepsy, immune cells interact with cells of the nervous system. Although the initiating events differ considerably, we hypothesize that there are common pathways in the crosstalk between the immune and nervous systems. We are studying this crosstalk to elucidate the influence of both pro-inflammatory and regulatory immune cells on neural cells. We also want to unravel the nervous system's capacity to regulate the immune system in the course of CNS diseases. The focus is on developing innovative, immune modulation-based therapeutic strategies to combat these devastating CNS diseases.

 

Research area E ⁞ Developmental disturbances

Coordinators: Grüters-Kieslich and Sigrist

Principal Investigators: Birchmeier, Brecht, Eickholt, Geiger, Grantyn, Haucke, Haynes, Heim, Heinemann, Heinz, Jentsch, Kloetzel, Larkum, Lewin, Poulet, Rosenmund, Scharff, Schmitz, Shoichet, Schülke-Gerstenfeld, Tarabykin, Treier, Vida, Winter

Over the last two decades, there has been a new understanding of the processes controlling the development of the nervous system. In particular, genes, genetic pathways, and molecular mechanisms important for patterning, differentiation and maturation have been identified. The rapid advances made by molecular and cellular developmental neurobiology in unravelling these mechanisms offer the opportunity to transfer these results into the clinical disciplines of neonatology, pediatric neurology, and pediatric neuroendocrinology to enable precise diagnostic procedures, genetic counselling, and potentially new therapeutic perspectives.

 

Research area F ⁞ Molecular neuropathology of ion channels and transporters

Coordinators: Plested and Schülke-Gerstenfeld

Principal Investigators: Brecht, Geiger, Grantyn, Haucke, Heinemann, Jentsch, Larkum, Lewin, Poulet, Rosenmund, Schmitz, Schroeder, Sigrist, Spahn, Vida

Numerous diseases of the CNS are based on hereditary defects in ion channels and transporters. Such defects interfere with normal protein function and disrupt both cellular processes as well as rapid signal transmission between nerve cells.  In vivo studies are supplemented with investigations into the biophysical and biochemical mechanisms of the channel receptor complex and its composition. High throughput screening methods are used to find new pharmacological substances affecting ion channels. Finally, extensive patient studies facilitate synergies between molecular and cellular biology as well as neuropathology. This in turn enables fundamental insights into ion channel pathophysiology and the development of new treatment concepts.

 

Research area G ⁞ Plasticity

Coordinators: Heinz and Rosenmund

Principal Investigators: Birchemeier, Brecht, Eickholt, Flöel, Geiger, Grüters-Kieslich, Haucke, Haynes, Heinemann, Jentsch, Kloetzel, Kühn, Larkum, Otte, Poulet, Scharff, Schmitz, Schülke-Gerstenfeld, Shoichet, Sigrist, Spahn, Tarabykin, Treier, Vida, Winter

This plasticity of synapses is instrumental in forming properly functioning neural circuits and is essential for learning and memory. Damaging events or genetic mutations often disrupt the balance of excitation and inhibition, which in turn causes major symptoms such as epilepsy, neuropsychiatric disorders and mental retardation. To analyze synaptic plasticity and circuitry function/dysfunction we perform highly integrative, collaborative investigations ranging from molecular manipulations to analyze networks and behavior. We also investigate pathophysiological mechanisms of mental disorders such as autism spectrum disorders and of patients with movement disorders undergoing deep brain stimulation.