Systems Biology of Pain

 

Head of Research Group: Prof. Manuela Schmidt

Foto: Frank Stefan Kimmel (https://www.fskphotography.de/)

Mission statement


Research in our laboratory is driven by our motivation to decipher the dynamics of protein networks underlying vertebrate somatosensation in health, development (aging) and disease (chronic pain). Methodologically, we combine molecular biology, biochemistry and latest proteomics techniques, electrophysiology, pharmacology, mouse models of painful pathologies and in vivo virus-mediated gene transfer.

This multidisciplinary approach has enabled us to reveal ion channel-associated signaling complexes (i.e. the interactome of TRPV1, TRPA1 and Piezo2 channels) with pathological relevance for pain. Moreover, in a quantitative systems biology approach, we investigate spatiotemporal proteome dynamics both in mice and humans. Our research lives from our fruitful collaborations with basic researchers and clinicians alike facilitating forward and reverse translation of our research results.

In this way we strive to gain mechanistic insights into developmental and pain-associated plasticity – an endeavor, which lies at the heart of both understanding the molecular signature of chronic pain and identifying novel drug targets.

Team

(to be updated soon)

Publication list

RESEARCH ARTICLES:

  1. Niklas Michel, Pratibha Narayanan, Orr Shomroni, Manuela Schmidt (2020). Maturational Changes in Mouse Cutaneous Touch and Piezo2-Mediated Mechanotransduction. Cell Reports. https://doi.org/10.1016/j.celrep.2020.107912. Editors´ Pick “Paper of the Week”, PainResearchForum
  2. Julia R. Sondermann, Allison M. Barry, Olaf Jahn, Niklas Michel, Reham Abdelaziz, Sebastian Kügler, David Gomez-Varela, Manuela Schmidt (2019). Vti1b promotes TRPV1 sensitization during inflammatory pain. PAIN. doi: 10.1097/j.pain.0000000000001418. Awarded with “1st prize for pain research 2019” (Förderpreis für Schmerzforschung), German Pain Society
  3. Allison M. Barry, Julia R. Sondermann, Jan-Henrik Sondermann, David Gomez-Varela and Manuela Schmidt (2018). Region resolved quantitative proteome profiling reveals molecular dynamics associated with chronic pain in the PNS and spinal cord. Front. Mol. Neurosci. doi: 10.3389/fnmol.2018.00259
  4. Pratibha Narayanan, Meike Huette, Galina Kudryasheva, Francisco J Taberner, Stefan Lechner, Florian Rehfeldt, David Gomez-Varela, Manuela Schmidt (2018). Myotubularin related protein-2 and its phospholipid substrate PIP2 control Piezo2-mediated mechanotransduction in peripheral sensory neurons. eLife. doi: 10.7554/eLife.32346
  5. Bruderer R, Bernhardt OM, Gandhi T, Xuan Y, Sondermann J, Schmidt M, Gomez-Varela D, Reiter L (2017).Optimization of Experimental Parameters in Data-Independent Mass Spectrometry Significantly Increases Depth and Reproducibility of Results. Mol Cell Proteomics. doi: 10.1074/mcp.RA117.000314
  6. Sandeep Dembla, Marc Behrendt, Florian Mohr, Christian Goecke, Julia Sondermann, Franziska M Schneider, Marlene Schmidt, Julia Stab, Raissa Enzeroth, …Dominik Oliver, Eleonora Zakharian, Manuela Schmidt, Johannes Oberwinkler (2017). Anti-nociceptive action of peripheral mu-opioid receptors by G-beta-gamma protein-mediated inhibition of TRPM3 channels. eLife. doi.org/10.7554/eLife.26280.001
  7. Bruderer R, Sondermann J, Tsou CC, Barrantes-Freer A, Stadelmann C, Nesvizhskii AI, Schmidt M, Reiter L, Gomez-Varela D. (2017). New targeted approaches for the quantification of data-independent acquisition mass spectrometry. Proteomics. doi: 10.1002/pmic.201700021
  8. Avenali L, Abate Fulas O, Sondermann J, Narayanan P, Gomez-Varela D, Schmidt M. (2016). Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons. Channels (Austin). 2016 Jun 30:1-9. doi: 10.1080/19336950.2016.1207025
  9. Narayanan P, Sondermann J, Rouwette T, Karaca S, Urlaub H, Mitkovski M, Gomez-Varela D, Schmidt M. (2016). Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons. J Proteome Res, 5;15(8):2676-87. doi: 10.1021/acs.jproteome.6b00235
  10. Rouwette T, Sondermann J, Avenali L, Gomez-Varela D, Schmidt M. (2016). Standardized profiling of the membrane-enriched proteome of mouse dorsal root ganglia provides novel insights into chronic pain. Molecular & Cellular Proteomics, doi: 10.1074/mcp.M116.058966.
  11. Coste B, Murthy SE, Marthur J, Schmidt M, Mechioukhi Y, Delmas P, Patapoutian A. (2015). Piezo1 ion channels pore properties are dictated by C-terminal region. Nature Communications 6; doi: 10.1038/ncomms8223
  12. Avenali L, Narayanan P, Rouwette T, Cervellini I, Sereda M, Gomez-Varela D, Schmidt M. (2014). Annexin A2 Regulates TRPA1-Dependent Nociception. J Neurosci. 34(44):14506-16. doi: 10.1523/JNEUROSCI.1801-14. Awarded with “1st prize for pain research 2015” (Förderpreis für Schmerzforschung), German Pain Society
  13. Matkovic T, Siebert M, Knoche E, Depner H, Mertel S, Owald D, Schmidt M, Thomas U, Sickmann A, Kamin D, Hell SW, Bürger J, Hollmann C, Mielke T, Wichmann C, Sigrist SJ. (2013). The Bruchpilot cytomatrix determines the size of the readily releasable pool of synaptic vesicles. J Cell Biol. 202(4):667-83. doi: 10.1083/jcb.201301072.
  14. Dubin AE, Schmidt M, Mathur J, Petrus MJ, Xiao B, Coste B, Patapoutian A. (2012). Inflammatory signals enhance piezo2-mediated mechanosensitive currents. Cell Rep. Sep 27;2(3):511-7.
  15. Gómez-Varela D, Schmidt M, Schoellerman J, Peters EC, Berg DK. (2012) PMCA2 via PSD-95 Controls Calcium Signaling by α7-Containing Nicotinic Acetylcholine Receptors on Aspiny Interneurons. J Neurosci. 16;32(20):6894-905.
  16. Coste B, Xiao B, Santos JS, Syeda R, Grandl J, Spencer KS, Kim SE, Schmidt M, Mathur J, Dubin AE, Montal M, Patapoutian A. (2012) Piezo proteins are pore-forming subunits of mechanically activated channels. Nature 19;483(7388):176-81.Tautenhahn R, Patti GJ, Kalisiak E, Miyamoto T, Schmidt M, Lo FY, McBee J, Baliga NS, Siuzdak G. (2011) metaXCMS: second-order analysis of untargeted metabolomics data. Anal Chem. 83(3):696-700.
  17. Tautenhahn R, Patti GJ, Kalisiak E, Miyamoto T, Schmidt M, Lo FY, McBee J, Baliga NS, Siuzdak G. (2011) metaXCMS: second-order analysis of untargeted metabolomics data. Anal Chem. 83(3):696-700.
  18. Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A. (2010) Piezo1 and Piezo2 Are Essential Components of Distinct Mechanically Activated Cation Channels Science, 330: 55-60
  19. Owald D*, Fouquet W*, Schmidt M, Wichmann C, Mertel S, Depner H, Christiansen F, Zube C, Quentin C, Körner J, Urlaub H, Mechtler K, Sigrist SJ. (2010) A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila. J Cell Biol. Feb 22;188(4):565-79; OD and FW contributed equally to this work.
  20. Gómez-Varela D, Kohl T, Schmidt M, Rubio ME, Kawabe H, Nehring RB, Schäfer S, Stühmer W and Pardo LA. (2010). Direct visualization of the lateral mobility of endogenous Eag1 channels in hippocampal synapses. PLoS One. Jan 25;5(1):e8858.
  21. Schmidt M, Dubin AE, Petrus MJ, Earley TJ, Patapoutian A (2009). Nociceptive signals induce trafficking of TRPA1 to the plasma membrane. Neuron 64(4):498-509.
  22. Grandl J, Hu H, Bandell M, Bursulaya B, Schmidt M, Petrus M, Patapoutian A (2008). Pore region of TRPV3 ion channel is specifically required for heat activation. Nat Neurosci. 11(9):1007-1
  23. Schmid A, Qin G, Wichmann C, Kittel RJ, Mertel S, Fouquet W, Schmidt M, Heckmann M, Sigrist SJ (2006). Non-NMDA-type glutamate receptors are essential for maturation but not for initial assembly of synapses at Drosophila neuromuscular junctions. J Neurosci. 26(44):11267-77.
  24. Swan LE*, Schmidt M*, Schwarz T, Ponimaskin E, Prange U, Boeckers T, Thomas U, Sigrist SJ (2006). Complex interaction of Drosophila GRIP PDZ domains and Echinoid during muscle morphogenesis. EMBO J. 25(15):3640-51. Swan LE and Schmidt M contributed equally to this work.
  25. Kittel RJ*, Wichmann C*, Rasse TM*, Fouquet W, Schmidt M, Schmid A, Wagh DA, Pawlu C, Kellner RR, Willig KI, Hell SW, Buchner E, Heckmann M, Sigrist SJ (2006). Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 19;312(5776):1051-4. KJR, WC, RTM contributed equally to this work.
  26. Wagh DA*, Rasse TM*, Asan E, Hofbauer A, Schwenkert I, Durrbeck H, Buchner S, Dabauvalle MC, Schmidt M, Qin G, Wichmann C, Kittel R, Sigrist SJ, Buchner (2006). Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. Neuron 16;49(6):833-44. WDA and RTM contributed equally to this work.
  27. Rasse TM, Fouquet W, Schmid A, Kittel RJ, Mertel S, Sigrist CB, Schmidt M, Guzman A, Merino C, Qin G, Quentin C, Madeo FF, Heckmann M, Sigrist SJ (2005). Glutamate receptor dynamics organizing synapse formation in vivo. Nat Neurosci. 8(7):898-905.
  28. Swan LE*, Wichmann C*, Prange U, Schmid A, Schmidt M, Schwarz T, Ponimaskin E, Madeo F, Vorbruggen G, Sigrist SJ (2004). A glutamate receptor-interacting protein homolog organizes muscle guidance in Drosophila. Genes Dev. 18(2):223-37. SLE and WC contributed equally to this work

 

REVIEW ARTICLES and BOOK CHAPTERS:

  1. David Gomez-Varela, Manuela Schmidt (2018). The Proteomics and Metabolomics of Pain—Opportunities for Systems Medicine. The Oxford Handbook of the Neurobiology of Pain, edited by John N. Wood. doi:10.1093/oxfordhb/9780190860509.001.0001
  2. David Gomez-Varela, Allison M Barry, Manuela Schmidt (2018). Proteome-based systems biology in chronic pain. Journal of Proteomics. doi:10.1016/j.jprot.2018.04.004
  3. Gomez-Varela D, Schmidt M. (2016). Exploring novel paths towards protein signatures of chronic pain. Molecular Pain, Commentary 2016 Dec 7;12. pii: 1744806916682242
  4. Rouwette T, Avenali L, Sondermann J, Narayanan P, Gomez-Varela D, Schmidt M. (2015). Modulation of nociceptive ion channels and receptors via protein-protein interactions - implications for pain relief. Channels (Austin). 4;9(4):175-85. doi: 10.1080/19336950.2015.1051270

Short CV - Manuela Schmidt

Curriculum Vitae Manuela Schmidt:
Born 1978 in Wasserburg/Inn, Germany

1997 - 2002

Diploma, Biology; University of Wuerzburg, Germany

2001 - 2002

Master, Neurosciences; International Max Planck Research School Neurosciences, Goettingen

2002 - 2006

PhD, Neurosciences; Supervisor: Prof. Dr. Stephan Sigrist
International Max Planck School Neurosciences, Goettingen, Germany

2007 - 2012

Postdoctoral fellow; Advisor: Prof. Ardem Patapoutian, PhD

TSRI (The Scripps Research Institute), La Jolla, California, USA

2012 - 2018

Independent Research Group Leader, Emmy Noether-Program, DFG

MPI of Experimental Medicine (MPIEM), Goettingen, Germany

2019 - 2020

W2-Professorship, Faculty of Biology and Psychology, University of Goettingen, Germany

Since Sept. 2020

Professorship for Pharmacology and Toxicology, Faculty of Life Sciences,

University of Vienna