Research in the Liedtke-Lab is centered around TRP (transient receptor potential) ion channels. TRP channels were first reported in drosophila in 1989. A mutation in trp was the cause for the phenotype of a transient receptor potential light response. Since then, they were shown in mammals, vertebrates, invertebrates and yeast as well, not in bacteria. The fascination of 1989, namely that they play a role in sensory transduction, yet their exact role in signal transduction awaits further clarification, still holds true. Based on the discoveries of the founding members of the TRPV (TRP- vanilloid) subfamily, OSM-9 (a C. elegans TRPV channel) and TRPV1 (a mammalian TRP channel, identified as the ionotropic receptor activated by capsaicin and other vanilloid), the osmotically activated TRPV channel TRPV4 was reported in 2000 by Liedtke et al. in a paper in Cell. In order to elucidate TRPV4's role in vivo, the gene was knocked out in mice (2003 PNAS paper by Liedtke and Friedman), and expressed as transgene in the nociceptive ASH sensory neuron in C. elegans, in the osm-9 mutant. Surprisingly, the mammalian channel directed defensive behavior in response to noxious osmotic and mechanical stimuli. Response behavior and physiology in mice is altered for the same modalities, as demonstrated by the phenotype of the trpv4-/- mice. Since coming to Duke University in 2004, Dr. Liedtke has set up an outpatient clinic specializing in diagnosis and treatment for patients suffering from neuropathic pain.
Based on the above discoveries, and dovetailing with the clinical interest in neuropathic pain, the focus of the Liedtke-laboratory is 1) deconstruction of the role of TRP ion channels and other critical molecular effectors in maintenance of hydromineral homeostasis, as regulated by the central nervous system 2) to reach an increased level of understanding of molecular transduction mechanisms in sensory neurons, with a focus on trpv4 (mammals) and osm-9 (C. elegans) 3) in relation to 2), to focus on the interaction of sensory neurons and innervated epithelia in airways, and to elucidate cellular and molecular mechanisms of their interaction, how this interaction is tuned by environmental stimuli (collaboration with the Simon lab) 4) deconstruction of signal transmission mechanisms in the spinal cord dorsal horn, a critical relay station of sensory afferents of the pain pathway, relaying peripheral afferents to the thalamus, hypothalamus and other CNS centers (amygdala).
Simon Lab at Duke University Medical Center
Turner BioSystems - Luminometer Grants Program
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