Lines of investigation
Specialized subsets of primary sensory neurons innervating different body tissues detect and transduce different environmental cues into itch, touch, temperature or pain information. When these signals eventually reach the brain, they generate the sensory percept and evoke the convenient physiological and behavioural responses for the survival of the animal. On its way to the brain, this sensory information undergoes an initial processing at the spinal cord. In healthy individuals, local excitatory and inhibitory spinal cord interneurons form modality specific processing microcircuits. These circuits dynamically tune down or amplify the sensory signals in response to other sensory modalities or to brain descending signals. However, in certain pathologies like nerve injury or in different inflammatory conditions, the normal processing at the spinal cord is altered and unconventional maladaptive circuits are wired up, resulting in chronic pain and itch. Due to the intrinsic complexity of the spinal cord circuitry, and the lack of an appropriate tool set for capturing and interrogating the spinal cord neuronal ensembles in behaving animals, our knowledge on the cellular and molecular substrates that constitute the sensory microcircuits and facilitate maladaptive changes are still largely unknown.
The overarching goal of the group is to define the spinal circuits associated with pain signals, to better understand processing alterations associated with chronicity, age and gender. In addition, we are trying to understand how different sensory modalities influence each other, as in the case of cold alleviating pain or itch, with the final aim of exploring and developing therapeutical strategies to improve quality of live in patients suffering from chronic itch and pain.
To achieve this objective, we seek to characterize the molecular identity and intrinsic electrophysiological properties of the interneurons that constitute these sensory microcircuits, as well as defining the changes they undergo in pathological states. We combine the development of minimally-invasive circuit marking and manipulation technologies with other state-of-the-art techniques, including different viral tracing approaches, optogenetics, whole spinal cord imaging and single-nucleus sequencing with well-stablished electrophysiological techniques.
Representative Publications
- OCaR1 endows exocytic vesicles with autoregulatory competence by preventing uncontrolled Ca2+ release, exocytosis, and pancreatic tissue damage. Tsvilovskyy , Ottenheijm , Kriebs , Schütz, Diakopoulos, Jha , Bildl, Wirth, Böck , Jaślan, Ferro , FJ Taberner ,Kalinina , Hildebrand , Wissenbach, Weissgerber , Vogt, Eberhagen, Mannebach, Berlin, Kuryshev, Schumacher ,Philippaert, Camacho-Londoño , Mathar, Dieterich, Klugbauer, Biel , Wahl-Schott , Lipp , Flockerzi , Zischka, Algül, Lechner , Lesina, Grimm, Fakler, Schulte , Muallem , Freichel J Clin Invest. 2024 134(7): e169428 https://doi.org/10.1172/JCI169428
- Contribution of mechanoreceptors to spinal cord injury–induced mechanical allodynia. Sliwinski, C; Heutehaus, L; Taberner, Francisco J.; Weiss, L; Kampanis, V; Tolou-Dabbaghian, B; Cheng, X; Motsch, M; Heppenstall, P; Kuner, R; Franz, S; Lechner, S; Weidner, N; Puttagunta, R PAIN 2024 165(6): 1336-1347 https://doi.org/10.1097/j.pain.0000000000003139
- The ion channel TRPM8 is a direct target of the immunosuppressant rapamycin in primary sensory neurons. Arcas JM, Oudaha K, González A, Fernández-Trillo J, Peralta FC, Castro-Marsal J, Poyraz S, Tabener F, Sala S, de la Peña E, gomis A, Viana F. British Journal of Pharmacology. 2024 First published: 13 May 2024 https://doi.org/10.1111/bph.16402
- Role of TMEM100 in mechanically insensitive nociceptor un-silencing. Timo A. Nees, Na Wang, Pavel Adamek, Nadja Zeitzschel, Clement Verkest, Carmen La Porta, Irina Schaefer, Julie Virnich, Selin Balkaya, Vincenzo Prato, Chiara Morelli, Valerie Begay, Young Jae Lee, Anke Tappe-Theodor, Gary R. Lewin, Paul A. Heppenstall, Francisco J. Taberner & Stefan G. Lechner Nat Commun. 2023 14, Art. 1899 https://doi.org/10.1038/s41467-023-37602-w
- Intrinsically disordered intracellular domains control key features of the mechanically-gated ion channel PIEZO2 Verkest, C., Schaefer, I., Nees, T.A., Wang, N., Jegelka, J.M., Taberner, F.J., Lechner, S.G. Nature Communications 2022 13(1): art 1365 http://doi.org/10.1038/s41467-022-28974-6
- Neuropathic pain caused by miswiring and abnormal end organ targeting. Gangadharan V, Zheng H, Taberner FJ, Landry J, Nees TA, Pistolic J, Agarwal N, Männich D, Benes V, Helmstaedter M, Ommer B, Lechner SG, Kuner T, Kuner R. Nature. 2022 606 (7912): 137-145 https://doi.org/10.1038/s41586-022-04777-z
- Identification of a population of peripheral sensory neurons that regulates blood pressure Morelli C,Castaldi L, Brown SJ, Streich LL, Websdale A, Taberner FJ, Cerreti B, Barenghi A, Blum KM, Sawitzke J, Frank T, Steffens LK, Doleschall B, Serrao J, Ferrarini D, Lechner SG, Prevedel R, Heppenstall PA. Cell Reports 2021 35(9) https://doi.org/10.1016/j.celrep.2021.109191
- USH2A is a Meissner’s corpuscle protein necessary for normal vibration sensing in mice and humans Schwaller F , Bégay V, García-García G, Taberner FJ, Moshourab R, McDonald B, Docter T, Kühnemund J, Ojeda-Alonso J, Paricio-Montesinos R, Lechner SG, Poulet JFA, Millan JM, Lewin GR Nat Neurosci 2021 24(1):74 https://doi.org/10.1038/s41593-020-00751-y
- SUMOylation of Enzymes and Ion Channels in Sensory Neurons Protects against Metabolic Dysfunction, Neuropathy, and Sensory Loss in Diabetes Agarwal N , Taberner FJ, Rangel Rojas D, Moroni M, Omberbasic D, Njoo C, Andrieux A, Gupta P, Bali KK, Herpel E, Faghihi F, Fleming T, Dejean A, Lechner SG, Nawroth PP, Lewin GR, Kuner R. Neuron 2020 107(6):1141 https://doi.org/10.1016/j.neuron.2020.06.037
- Structure-guided examination of the mechanogating mechanism of PIEZO2 Taberner FJ,Prato V, Schaefer I, Schrenk-Siemens K, Heppenstall PA, Lechner SG Proc Natl Acad Sci USA 2019 116(28):14260 https://doi.org/10.1073/pnas.1905985116