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Dr. Nuška Tschammer

Department of Chemistry and Pharmacy
Emil Fischer Center
Friedrich Alexander University
Schuhstraße 19
D-91052 Erlangen
Germany

Room: 2.014
nuska.tschammer@medchem.uni-erlangen.de
Tel.: +49-(0)9131-85-23931

RESEARCH INTEREST

Chemokine receptors are G-protein coupled receptors (GPCRs), which regulate the immune cell trafficking and control a multiplicity of processes in health and disease, ranging from immunosurveillance to inflammation, and from viral infection to cancer. Small-molecular-weight compounds which disrupt cell migration appear particularly promising for the management and treatment of inflammatory diseases and cancer. Additionally, viruses like HCMV encode viral G-protein coupled receptors (vGPCRs), which couple very efficiently to signalling networks and are often highly homologous with hosts’ chemokine receptors. Constitutive signalling (agonist-independent activity) of vGPCRs augments virus survival, host invasion and, in some cases, oncogenesis or cardiovascular disease. The development of small-molecular-weight compounds which reverse the constitutive activity of vGPCRs remains challenging task. Combining the development of allosteric modulators with the mutagenesis, photoaffinity labeling, mass spectrometry and molecular modeling of human chemokine receptors and viral chemokine receptor homologs, my research group aspires to identify new molecular scaffolds and to develop chemical tools, which will assist in deciphering the enigmatic role of chemokine receptors and their mimics in the disease states. These tools are than used for the investigations of receptor dynamics and ligand-induced conformational changes in live cells and artificial systems by different spectroscopic methods. The mechanism of allosteric modulation raises the possibility of designing novel ligands, which differentially activate downstream signaling pathways and thus promote desired therapeutic action with reduced unwanted effects.


CURRICULUM VITAE

EDUCATION AND PROFFESIONAL ACTIVITIES

  • Dec. 2011     Habilitandin, Department of Chemistry and Pharmacy, Emil Fisher Center, Friedrich-Alexander University of Erlangen - Nürnberg
  • 2011-2011    Senior Researcher/Independent Research group Leader, Department of Chemistry and Pharmacy, Emil Fisher Center, Friedrich-Alexander University of Erlangen - Nürnberg
  • 2008-2010    Posdoctoral Researcher, Department of Chemistry and Pharmacy, Emil Fisher Center, Working Group of Prof. Dr. Peter Gmeiner, Friedrich-Alexander University of Erlangen - Nürnberg, Germany 
  • 2004-2007    Biomolecular Science Center, Burnett College of Biomedical Sciences, University of Central Florida, Orlando, USA: PhD in Biomolecular Sciences; Working Group of Dr. Annette Khaled 
  • 1999-2002    Faculty of Chemistry and Chemical Engineering, University of Maribor, Slovenia:  Master of Science (chemical technology – chemistry of  polymer membranes). 
  • 1999-1999    Phillips - University of Marburg, Department of Biology, Project Work, Working Group of Prof. Dr. Harald Plachter
  • 1998-1998    Mississippi State University, Department of Biology, Summer Research, Working Group of Prof. Dr. Ronn G. Altig
  • 1993-1998    Pedagogical Faculty, University of Maribor, Slovenia: Maribor, Slovenia; biology and chemistry; Degree: diploma (bachelor) degree in biology and chemistry
  • 1989-1993    High School Programme: Celje, Slovenia; Sciences and mathematics

COLLABORATIONS 

  • Prof. Dr. Jesus Giraldo, Institute of Neuroscience, University of Barcelona, Spain
  • Prof. Dr. Armin Buschauer, Institute of Pharmacy, University of Regensburg, Germany
  • Dr. Peter Kolb, Medicinal Chemistry, University of Marburg, Germany
  • Prof. Dr. Markus Heinrich, Chair of Medicinal Chemistry, University of Erlangen/Nürnberg, Germany
  • Prof. Dr. Thomas Stamminger, Institute for Clinical and Molecular Virology, University Hospital Erlangen, Germany
  • Prof. Dr. Terry Kenakin, Department of Pharmacy, University of North Carolina,, USA
  • Prof. Dr. Annette Khaled, Biomolecular Science Center, University of Central Florida, Orlando, USA
  • Prof. Dr. Otto Phanstiel, Department of Chemistry, Univeristy of Central Florida, Orlando, USA

FUNDING

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TEACHING

  • In Vitro Assay-Systems I-III; Molecular Life Science - Masterphase: Modul Drug Discovery
  • Electives Medicinal Chemistry: Biopharmacy/Bioassays

VOLUNTARY WORK 

  • 2011 - dato:  Advancement of Women/Frauenförderung: E-Mentoring-Program CyberMentor for MINT-Field (Mathematics, Informatics, Life Sciences and Technique)

STUDENTS SUPERVISED

  • Viachaslav Bernat, doctoral student, CXCR3 Project (co-supervisor Prof. Dr. Heinrich)
  • Ana Kralj, doctoral student, US28 Project (co-supervisor Prof. Dr. Heinrich)

BIBLIOGRAPHY (selected publications)

  1. KRALJ, A., WETZEL, A., MAHMOUDIAN, S., STAMMINGER, T., TSCHAMMER, N., HEINRICH, M., Identification of novel allosteric modulators for the G-protein coupled US28 receptor of human cytomegalovirus. Bioorg. Med. Chem. Lett., 2011, In Press, doi:10.1016/j.bmcl.2011.06.120
  2. KOSCHATZKY, S., TSCHAMMER, N., GMEINER, P., Cross-receptor interactions bewteen dopamine D2L and neurotensin NTS1 receptors modulate binding affinities of dopaminergics. ACS Chem. Neurosci., 2011, 2, 308-316, doi:10.1021/cn200020y
  3. Einsiedel, J., HELD, C., Maud, h., Plomer, M., tschammer, n., hübner, h., Gmeiner, p., Discovery of highly potent and NTS2 selective neurotensin mimetics. J. Med. Chem., 2011, 54, 2915-2923, doi:10.1021/jm200006c
  4. tschammer, N., ELSNER, J., GÖTZ, A., EHRLICH, K., SCHUSTER, S., Ruberg, M., KüHHORN, J., Thompson, D., Whistler, J., Hübner, H.,Gmeiner, P., Highly Potent  5-Aminotetrahydropyrazolopyridines: Enantioselective Dopamine D3 Receptor Binding, Functional Selectivity, and Analysis of Receptor-Ligand Interactions, J. Med. Chem., 2011, 54, 2477-2491, doi:10.1021/jm101639t
  5. Löber, S., HÜbner, H., Tschammer, N., Gmeiner, P., Recent advances on the search of D3 and D4 selective drugs: probes, models and candidates, Trends in Pharm. Sci., 2011, 32 (3), 148-157, doi:10.1016/j.tips.2010.12.003 
  6. TSCHAMMER, N., BOLLINGER, S., KENAKIN, T., Gmeiner, p., Histidine 6.55 is a major determinant of ligand biased signaling in dopamine D2L receptor. Mol.Pharmacol. 2011, 79 (3), 575–585, doi:10.1124/mol.110.068106
  7. KITTIPATARIN, C., TSCHAMMER, N.,KHALED, A.R., The interaction of LCK and the CD4 co-receptor alters the dose response of T-cells to interleukin-7. Immunol. Lett., 2010. doi:10.1016/j.imlet.2010.04.007
  8. TSCHAMMER, N., DÖRFLER, M., HÜBNER, H., GMEINER, P., Engineering a GPCR-ligand pair that stimulates the activation of D2L by dopamine. ACS Chemical Neuroscience, 2010, 1,25-35. doi:10.1021/jcn900001b
  9. EHRLICH, K., GÖTZ, A., BOLLINGER, S.,TSCHAMMER, N., HÄRTERICH, S., HÜBNER, H., GMEINER, P.,Dopamine D2, D3 and D4 selective phenylpiperazines as molecular probes to explore the origins of subtype specific receptor binding. J. Med. Chem., 2009, 52(15): 4923-4935. doi:10.1021/jm900690y
  10. LÖBER, S., TSCHAMMER, N., HÜBNER, H., MELIS, M.R., ARGIOLAS, A., GMEINER, P.,The azulene framework as a novel bioisostere: Design of a potent dopamine D4 receptor ligands inducing penile erection. ChemMedChem, 2009, 4(3): 325-328. doi:10.1002/cmdc.200800395
  11. DÖRFLER, M., TSCHAMMER, N., HAMPERL, K., HÜBNER, H., GMEINER, P., Novel D3 Selective Dopaminergics Incorporating Enyne Units as Nonaromatic Catechol Bioisosters: Synthesis, Bioactivity, and Mutagenesis Studies. J. Med. Chem., 2008, 51(21): 6829-6838. doi:10.1021/jm800895v
  12. KAUR, N., DELCROS, J., CHEHTAN, M., TSCHAMMER, N., KHALED, A.R., PHANSTIEL, O., 4th, A comparison of chlorambucil- and xylene- containing polyamines leads to improved ligands for accessing the polyamine transporter. J. Med. Chem., 2008, 51(5): 1393-1401. doi:10.1021/jm070794t 
  13. KHALED, A.R., TSCHAMMER, N., ZHANG, G., SELBY, T.A., Structural Transitions that Regulate the Apoptotoc Activity of BAX are Dependent on ist C-terminal Alpha-9 Helix. Cell Death, Self-Renewal and Cell Cycle in Development (84.1-84.13). J.Immunol., 2007, 178:S117.
  14. TSCHAMMER, N., G., SELBY, T.A., KHALED, A.R., The Membrane-binding Activity of the Apoptotic Protein, BAX, is Regulated Through Novel Intramolecular Interactions, Cytokine, 2007, 39(1): 42-43.  doi:10.1016/j.cyto.2007.07.159
  15. GUO, S., TSCHAMMER, N., MOHAMMED, S., GUO, P., Specific delivery of therapeutic RNAs to cancer cells via the dimerization mechanism of phi29 motor pRNA. Hum. Gene Ther., 2005, 16(9): 1097-1109. doi:10.1089/hum.2005.16.1097
  16. TSCHAMMER, N., GUO, P.X., KHALED, A.R., Use of the bacteriophage phi29 packing RNA as nanovehicle for targeted delivery of therapeutic RNAs to CD4+ T-cells, FASEB J., 2005, 19(5): A1405-A1405.
  17. VOGRIN, N., STROPNIK, C., MUSIL, V. BRUMEN, M., The wet phase separation: the effect of cast solution thickness on the appearance of macrovoids in the membrane forming ternary cellulose acetate/acetone/water system. J. Membr.Sci.., 2002: 207, 139-141.  doi:10.1016/S0376-7388(02)00119-9