Lab of Wolfgang Liedtke MD. PhD.
understanding sensory transduction and pain
We study sensory neurobiology of pain with focus on calcium-related signaling mechanisms. To better understand chronic, pathological pain at the organismal level, we use genetic model organisms from invertebrate to rodent. Our approaches include behavioral, structural and molecular studies, advanced imaging, and patch-clamp electrophysiology.
The Liedtke-Lab is housed in the Duke University Dept. of Neurology. Dr. Wolfgang Liedtke (PI) is also affiliated with the Depts. of Neurobiology and Anesthesiology. In addition, he was the first hire in the Duke Center for Translational Neuroscience.
The experimental agenda of the Liedtke Lab is in keeping with Dr. Liedtke's clinical focus on chronic trigeminal pain disorders in his outpatient clinics in the Duke Neurology Clinics for Headaches, Head-Pain and Trigeminal Sensory Disorders. His clinics draw nation-wide referrals.
We aim to deconstruct sensing mechanisms at the molecular, cellular, organ/systems and organismal level. The sensory system most pertinent for our mission is the nociceptive system, which is necessary to evoke pain in conscious animals including humans, yet directs aversive behavior in virtually all animals that have a nervous system. Because of the relevance for pain and nociception, besides tonicity and mechanical stimuli, patho-physiologically relevant modulatory co-stimuli such as inflammatory and tissue-injury mediators are also being considered. To fulfill this mission, the Liedtke-Lab is focused on the TRPV4 ion channel as a key signaling molecule. TRPV4 was first described (as vanilloid-receptor related osmotically activated receptor, VR-OAC) in a landmark Liedtke-et-al paper in Cell in October 2000, the first account of its function in live animals in two PNAS papers in 2003. Therefore, the focus of the Liedtke-Lab remains on transduction mechanisms of TRPV4, with additional attention dedicated to its invertebrate orthologue OSM-9 (C. elegans). The unexpected discovery of TRPV4 as a UVB-receptor in skin keratinocytes is certainly a recent highlight of discovery in the Liedtke-Lab. Other prominent work led to the definition of TRPV4 as a rational therapeutic target for trigeminal pain and inflammatory disorders. Novel small-molecule blockers of TRPV4 have been generated in the Liedtke-Lab.
Related to “noci-transmission”, neural transmission of pain-evoking stimuli is also being explored: The Liedtke-Lab is also interested in calcium-dependent gene-regulation of Kcc2, which codes for a chloride extruding transporter molecule in CNS neurons. Dysregulation of this gene has relevance for chronic pain, epilepsy and neural injury.
to chronic joint dysfunction and joint pain, the Liedtke-Lab has engaged in a long-standing, fruitful and successful collaboration with prominent skeletal bio-engineer Dr. Farshid Guilak, leading to specific novel insights into molecular mechanisms of osmo- and mechanotransduction in cartilage, implicating mechanosensory TRPV4 and Piezo1 and -2 channels for the continuum of mechanical cues that joint cartilage is subject to, from physiologic load to injurious stress.
Copyright @WLiedtke 2016