zur Förderung biomedizinischer Forschung
Prof. Rohini Kuner
C.H.S. Research Award 2005
|1995-1998||Postdoc ZMBH, University of Heidelberg and Department of Molecular Neurobiology Max-Planck-Institut for Medical Research, Heidelberg|
|1998-2000||Scientist, BASF-Lynx AG, Heidelberg|
|2000-2001||Scientist, Pharmacology Institute, University of Heidelberg|
|2002-||Group leader of an independent, DFG-financed Emmy Noether-program group Pharmacology Institute, Univ. Heidelberg|
|2005||Habilitation, Medical faculty of the University of Heidelberg|
|2006||Appointment as a professor at the University of Heidelberg|
Our research interests are mainly focused on understanding the molecular mechanisms underlying chronic pain disorders, with emphasis on inflammatory pain. Our methodological strategy lies in investigating the functional consequences of selective molecular perturbations at the level of synaptic processes and electrical activity of single neurons, at the level of sensorimotor networks by using electrophysiological approaches or via calcium imaging on populations of spinal neurons and finally at the level of pain-related behaviour in awake, unrestrained animals. A majority of current projects involve conditional, region-specific modification of genes encoding receptors or signaling mediators in pain pathways, with emphasis on molecules implicated in activity-dependent plasticity processes. Transgenic mice which lack receptors of important neuromediators such as cannabinoid receptors, GABA-B receptors, glutamate receptors or endothelin receptors or their key signaling effectors, such as G-proteins or protein kinases in a temporally and spatially-controlled manner were created using the Cre-loxP approach. Recently, we have also started working on the development of novel therapeutic approaches for chronic pain disorders, using viral gene delivery vectors and in-vivo RNAi approaches in mice.
In current and future projects, we are dedicating our efforts towards understanding the molecular mechanisms underlying pain disorders which are clinically very relevant and resistant to conventional therapy, such as knee arthritis, chronic pancreatitis and tumor-induced pain in collaboration with clinical departments of the university. Structural plasticity of nerves in disease states is theme central to several of these diseases. In order to study the functional aspects of such structural changes, we would like to apply imaging methods in living tissue. Towards this end, we have established a mouse line expressing the live fluorescent label, EGFP solely in nociceptive fibers. Using funds awarded by the Chica and Heinz Schaller Stiftung, we plan on studying molecular mechanisms underlying dynamic changes in nociceptors in disease states using these mice.
Feldemeyer D., Kask K., Brusa R., Kornau H.C., Kolhekar R., Rozov A., Burnashev N., Jensen V., Hvalby O., Sprengel R. and Seeburg P.H. Neurological dysfunctions in mice expressing different levels of the Q/R site-unedited AMPAR subunit GluR-B. Nature Neuroscience 2(1):57-64, 1999.
Kuner R., Kohr G., Grunewald S., Eisenhardt G., Bach A. and Kornau H.C. Role of Heteromer formation in GABA-B receptor function. Science 283, 74-77, 1999.
Swiercz JM*, Kuner R*, Behrens J, Offermanns S. Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology. Neuron, 35(1):51-63, 2002 * equal contribution
Kuner R, Swiercz JM, Zywietz A, Tappe A, Offermanns S. Characterization of the expression of PDZ-RhoGEF, LARG and Galpha12/Galpha13 proteins in the murine nervous system. Eur J Neurosci., 16(12):2333-41, 2002.
Dreyer J, Hirlinger D., Müller-Esterl W, Oess S , Kuner R Spinal upregulation of the nitric oxide synthase-interacting protein NOSIP in a rat model of inflammatory pain, Neurosci. Lett, 350(1):13-16, 2003
Kuner R, Teismann P, Trutzel A, Naim J, Richter A, Schmidt N, Ahsen O, Bach A, Ferger B, Schneider A, TorsinA protects against oxidative stress in COS cells and PC12 cells, Neurosci. Lett., 350(3):153-156, 2003
Kuner R, Teismann P, Trutzel A, Naim J, Richter A, Schmidt N, Bach A, Ferger B and Schneider A. TorsinA, the gene linked to early-onset dystonia, is upregulated by the dopaminergic toxin MPTP in mice, Neurosci. Lett., 355(1-2):126-30, 2004
Agarwal N., Offermanns S. and Kuner R. Conditional gene targeting in neurons of the dorsal root ganglia and trigeminal ganglia, Genesis, 38/3: 122-129, 2004
Worzfeld T., Püschel A., Offermanns S., Kuner R. Plexin-B family members demonstrate non-redundant expression patterns in the developing mouse nervous system: A anatomical basis for morphogenetic effects of Sema4D during development, Eur J Neurosci., 19(10):2622-32, 2004
Swiercz J.M., Kuner R. & Offermanns S. Plexin-B1/RhoGEF-mediated RhoA activation involves the receptor tyrosine kinase ErbB-2, J. Cell Biol., 165(6): 869-80, 2004
Hartmann B., Ahmadi S., Heppenstall P., Zeilhofer H.U., Lewin G., Schott C., Seeburg P.H., Sprengel R. & Kuner R. The AMPA receptor subunits, GluR-A and GluR-B reciprocally modulate spinal synaptic plasticity and inflammatory pain, Neuron, 44(4): 637-50, 2004
Dreyer J, Schleicher M, Tappe A, Schilling K, Kuner T, Kusumawidijaja G, Müller-Esterl W, Oess S and Kuner R. (NOS)-interacting protein interacts with neuronal NOS and regulates its distribution and activity, J. Neurosci., 24(46): 10454-10465, 2004
Kuner R., Groom A., Bresink I., Kornau H.C., Stefovska V., Müller G., HartmannB., Tschauner K., Waibel S., Ludolph A.C., Ikonomidou C., Seeburg P.H. & Turski L. Late-onset motoneuron disease caused by transgenic expression of a functionally modified AMPA receptor subunit, Proc. Natl. Acad. Sci. USA. 102(16):5826-31, 2005
Tappe A. und Kuner R. Regulation of motor performance and striatal function by synaptic scaffolding proteins of the Homer1 family, Proc. Natl. Acad. Sci. USA. 103(3):774-9, 2005
Reviews and Book Chapters
Kuner R., Groom A., Bresink I., Kornau H.C., Stefovska V., Müller G., Hartmann B.,Tschauner K., Waibel S., Ludolph A.C., Ikonomidou C., Seeburg P.H. & Turski L. Mechanisms of disease: Late-onset motoneuron disease caused by transgenic expression of a functionally modified AMPA receptor subunit, Ann. N.Y. Acad. Sciences, 1053:269-86, 2005
Kuner, R., Nociception, in Encyclopedic Reference of Molecular Pharmacology, S. Offermanns and W. Rosenthal (Eds.), Springer Verlag, p658, 2003
Gebhart G.F., Kuner R., Jones R.C.W. and Bielefeldt K., Visceral Hypersensitivity, in Hyperalgesia: Molecular Mechanisms and Clinical Implications, Progress in Pain Research and Management, Vol. 30, Eds. H. Handwerker and K. Brune, IASP Press, Seattle, 2004
Kuner R, Genetic approaches for the study of pain, in Molecular Pain, M. Zhuo and G.F. Gebhart (Eds.), Higher Education Press, China, in press, 2006
Ph.Dr. Rohini Kuner
Im Neuenheimer Feld 366
Homepage: Rohini Kuner; Pharmakologie Universität Heidelberg