Welcome to the website of the Lampert Lab!
At the Institute of Physiology, the core area of our research group is the field of neurophysiology.
Within an international team of scientists from various disciplines, we focus on sodium channels and the excitability of cells, in particular with the relationship between sodium channels and pain. Since sodium channels are essentially responsible for nerve excitation, changes in these channels may modulate pain.
Since voltage-gated sodium channels trigger action potentials, they are essentially responsible for the excitability of neurons. We investigate this channel and its physiological structure-function relationship as monomers and dimers.
Based on recently published CryoEM structures, we analyze the switching properties and altered pharmacology of sodium channel mutations in the context of cardiac arrhythmias, drug side effects, inflammatory neuropathies (including small fiber neuropathy), pain syndromes, as well as complex diseases such as schizophrenia or autism, as these can be associated with pathological variants or regulations of the chanal.
Peripheral neurons contain a variety of different subtypes of sodium channels. We also investigate their role in various sensory qualities within the Research Training Group MultiScale/MultiSenses.
Schematic representation of the opening of the sodium channel
The voltage-gated sodium channel Nav1.7 is significantly involved in the perception of potentially painful stimuli by peripheral neurons. Mutations of this channel may lead to pain syndromes, such as erythromelalgia. The erythromelalgia mutation Q875E creates a salt bridge within the channel molecule that stabilizes the voltage sensor of domain I in the activated position (metaphorically illustrated here by magnets).Thus, the Q875E mutation is likely to cause hyperexcitability and pain. This interaction between two chanal domains is probably the structural basis for a new mechanism underlying this pain disorder. Further information on this work can be found here and a graphical processing of our data can be found here.
Pain research currently suffers from a translation problem: pathomechanisms or therapies of mice are often ineffective in humans. In psychiatry, reliable preclinical models are rare. Therefore, a human cellular system is needed. We therefore work with induced pluripotent stem cells (iPS cells) from patients and subjects and thus generate sensory peripheral neurons and central nerve cells. Using electrophysiological methods, we investigate the excitability – and thus the relevant function – of these cells and can thus read the consequences of genetics, pharmacology and other manipulations directly in the functional pathophysiology of the cells. We are particularly interested in peripheral and neuropathic pain syndromes, but also schizophrenia and autism.
You can find out more about our stem cell research in this video of the Stem Cell Network NRW:
In collaboration with Prof. Laura De Laporte from the DWI (Leibniz Institute for Interactive Materials), we are working within the Research Training Group ME3T on a 3D innervated skin model based on hydrogels in order to investigate the altered keratinocyte-nerve interaction and neuronal excitability, e.g. in inflammation or genetic diseases.
In order to use cell models as close as possible to humans, we also use sensory neurons of the pig, which we characterize in detail electrophysiologically and genetically.
Intense interactions between basic scientists and clinicians build the basis for the development of new therapies.
In the BMBF consortium Bio2Treat we are developing a PainWatch together with our partners. We combine the biometric data of pain patients obtained in this way with electrophysiological data from iPS cells. Using machine learning approaches, we are working with our partners (Prof. Andreas Schuppert from the Institute of Computational Biomedicine and Grünenthal AG) to improve the diagnosis, prognosis and future treatment options for chronic pain patients.
In the Sodium Channel Network Aachen, SCNAachen, we are researching the basics of personalized medicine for SFN (Small Fiber Neuropathy) patients in a larger consortium. The effects of mutations in the channels on neuronal excitability are investigated. With the data obtained, we want to be able to predict what effects sodium channel variants can have on analgesics.
Using a high-throughput patch robot (SyncroPatch 381i), we study the biophysics of sodium channel variants of patients and perform pharmacological tests to potentially identify substances that can modify channel properties in a mutation-specific manner.
In cooperation with Prof. Namer (IZKF Junior Research Group Aachen), who conducts microneurographic recordings on the subject/patient, we form a bridge from basic research to the clinic.
The University Hospital RWTH Aachen is a non-profit institution whose research is financed by grants from the federal and state governments.
In order to be able to conduct excellent research with the aim of personalized therapy, we need additional support from organizations and partners from the public sector, industry and the healthcare industry.
Current third-party funded consortia: