Project Details
Projekt
Methods core and training unit
Applicants
Professor Dr. Alexander Brack; Professor Dr. Mirko Pham; Professor Dr. Nicolas Schlegel; Professorin Dr. Nurcan Üçeyler
Subject Area
Molecular and Cellular Neurology and Neuropathology
Anaesthesiology
Anaesthesiology
Term
since 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 426503586
The central project Z focuses on three interlinked goals: It establishes a training program for Clinician Scientists who are committed to a dual career and who require a structured program of scientific training. Each Clinician Scientist will be paired with an established researcher as a mentor. Secondly, three core units will be launched providing key research methods utilized by all patient centered projects of this proposal: 1) high-resolution structural and functional human MR nerve and dorsal root ganglion (DRG) imaging, 2) a skin biopsy analysis platform, 3) a blood analysis platform, collecting core data of all clinical projects. Thirdly, two longitudinal studies will be established with patients with resolving and non-resolving pain. Groups of patients will be studied for each disease entity at defined time points using deep phenotyping and methods established in the core units. The clinical studies will also allow structured exploration of mechanisms underlying resolution detected in the basic science-oriented projects.The educational aim of Z is to qualify Clinician Scientists for pain research along these methods, including key methods of pain research today and such that will likely shape the scientific landscape of pain research in the future. The core unit MR imaging provides several novel methods of high-resolution structural and functional imaging of the postganglionic peripheral nervous system including the DRG, enabling high-resolution nerve imaging in humans. For the first time, structural and functional injury of the human PNS will be shown by direct observations. The core unit for skin and blood analysis will develop, refine, and use standardized methods to assess potential biomarkers and, in general, structures and mediators that are associated with pain resolution. We will focus on the balance of pro- and anti-inflammatory factors, on growth factors and lipid chemistry. In the patient-centered projects of this proposal (P1, P2, P3) and in the two clinical observational studies of Z (CRPS and CPIP), specific hypotheses will narrow down peripheral candidate structures or mediators of neuropathic pain resolution. The data derived from the different independent imaging and non-imaging studies obtained by the work-packages and the patient related outcome measures will be analyzed by advanced bioinformatic modelling.In this project we aim at generating, characterizing, and analyzing iPSC-derived sensory neurons and Schwann cells from patients with neurofibromatosis (NF) and bortezomib-induced peripheral neuropathy with a genetic background (PKNOX1 polymorphism) to understand the underlying pathomechanisms of pain and pain resolution in an in vitro disease model.
DFG Programme
Clinical Research Units
