The long term goal of our research group is to identify and characterize novel genes that underlie development, function and pathologies of the nervous system. To this end, we focus on the genetic basis of rare disorders in humans, and use a multidisciplinary approach including behavioral studies, imaging and molecular/biochemical assays in animal models to study different genetic mutations and understand how they contribute to human pathology. The identification of novel genes and elucidation of their regulatory networks are essential in understanding how dysfunctions manifest themselves in neurological pathologies, and to harness those discoveries for the development of efficient therapeutic agents.
Understanding peripheral neuropathies
Congenital insensitivity to pain with anhidrosis (CIPA) is an inherited and rare type of peripheral neuropathy marked by a complete absence of pain perception. By deciphering the pathophysiology of this disease and characterizing the key molecular players, we aim to provide novel targets for future therapy. While short-term sensation of pain has a beneficial and protective function, it can develop into a chronic pathological state, lasting for months to years. Although our understanding of the molecular mechanisms underlining nociceptive processing has progressed significantly, effective and non-habit forming therapeutics are still lacking. By detailed analysis of this family of disorders, we aim to identify novel therapeutic targets for pain management relevant for a larger population.
Synaptic plasticity underlying neurodevelopmental disorders
A synapse is a functional unit connecting two neurons, and in relevant regions of the brain is thought to be the epicenter of memory storage. So-called ‘synaptic plasticity’, the ability of the synapse to undergo substantial structural and functional remodeling indispensable for its function, is orchestrated by a molecular network of complex intra- and extracellular events. A posttranslational modification, ubiquitination, for example, has recently gained ground as an important event during learning-dependent synaptic activity. A mutation in one E3 ubiquitin ligase has been shown to cause a neurodevelopmental disorder resulting in intellectual disability, spasticity and abnormal gait in young patients. We find that mice lacking this ligase have a remarkably similar phenotype to patients and are an ideal model to study the molecular neuropathology of this disease.