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1
Dr. Martina Schmidt
Personal data
Name
Date/Place of birth
Marital status
Addresses
private
professional
2
Education / Degrees
1970 - 1974
1974 - 1983
May 1983
1983 - 1989
February 1989
1989 - 1992
December 1992
June 1999
December 2000
February 2001
3
Martina Schmidt
13 December, 1963, Gelsenkirchen, Germany
married
van Eedenlaan 14, 9752 GK Haren, The Netherlands
+31 - 50 - 7078163
phone
+31 - 6 - 5575 7924
mobile
Professor of Molecular Pharmacology
Rosalind Franklin Fellow
Department of Molecular Pharmacology
University of Groningen, Anton Deusinglaan 1
9713 AV Groningen, Netherlands
phone: +31 - 50 - 363 3322
Fax: +31 - 50 - 363 6908
m.schmidt@rug.nl
Elementary school, Herten
Gymnasium, Herten
Gymnasium Examination
Study Biology, Ruhr-Universität Bochum
Master’s Degree Biology
Graduate student in the Institut für Physiologische
Chemie, Ruhr-Universität Bochum, Promotor Prof. Dr.
L.M.G. Heilmeyer Jr., Charakterisierung von
Phosphatidylinositol 4-Kinasen und Phosphatidylinositol 4-Phosphat 5-Kinasen aus Rinderhirn
Ph.D. Degree (graduation to Dr. rer. nat., cum laude)
Fachpharmakologin of the Deutsche Gesellschaft für
Experimentelle und Klinische Pharmakologie und
Toxikologie (DGPT)
Habilitation (graduation to D.Sc.). Habilitationsarbeit:
Molekulare Mechanismen der Phospholipase DStimulation durch membranständige Rezeptoren
Venia legendi in Pharmacology and Toxicology
Academic employment
1993
1993 - 1998
1998 - 2001
2002 - 2004
Post-doc fellow, Institut für Physiologische Chemie,
Ruhr-Universität Bochum
Post-doc fellow, Institut für Pharmakologie,
Universitätsklinikum Essen
wissenschaftliche Assistentin [C1], Institut für
Pharmakologie, Universitätsklinikum Essen
wissenschaftliche Oberassistentin [C2], Institut für
Pharmakologie, Universitätsklinikum Essen
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Dr. Martina Schmidt
December 2004 - December 2005
December 2005
- September 2006
4
Awards and Distinctions
February 2002
August 2004
January 2005
June 2005
5
Visiting scientist, Dept. Pharmacology &
Pharmacotherapy and Dept. Anatomy & Embryology,
Academic Medical Center, University of Amsterdam
Assistant Professor, Dept. of Molecular Pharmacology,
University of Groningen
Associate Professor of Molecular Pharmacology
(Adjunct-hoogleraar)
Ruf for a C3-Professorship
"Pharmakologie und Toxikologie", Universität Freiburg,
Germany, primo loco
C3-Professorship
"Pharmakologie und Toxikologie", Universität Ulm,
Germany, tertio loco
Forschungsstipendium Deutsche
Forschungsgemeinschaft, project Physiologische Rolle
von Epac-Proteinen im kardiovaskulären System
Ruf for a W2-Professorship
"Physiologische Chemie", Universität Halle, Germany,
primo loco
September 2005
Rosalind Franklin Fellowship, University of Groningen
January 2006
Rosalind Franklin Penning, University of Groningen
October 2007
Organon Prijs voor Farmacologie
Additionals
Reviewer of grant proposals and manuscripts
- Cancer Research UK, Deutsche Forschungsgemeinschaft, Interne Forschungsförderung
Universitätsklinikum Essen, Scottish Hospital Endowments Research Trust
-
Biochemical Journal, Biochimica et Biophysica Acta, Brain Research, British Journal
of Pharmacology, European Journal of Pharmacology, FEBS Letters, Immunobiology,
Molecular Pharmacology, Nature Signaling Gateway, Naunyn-Schmiedeberg’s
Archives of Pharmacology
Professional qualifications
March 1995
September 1998
Juni 2007
Course Radiation Safety (Fachkundegruppe S4.1)
Qualification as Projektleiter (PL) und Beauftragte für
die biologische Sicherheit (BBS) und GentechnikSicherheitsverordnung
Certificate cursus proefdierkunde
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Dr. Martina Schmidt
Membership professional societies
since 1996
Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und
Toxikologie
since 1999
American Society for Biochemistry and Molecular Biology
since 2004
American Society for Microbiology
since 2004
Deutscher Hochschulverband
since 2004
Nederlandse Vereniging voor Farmacologie
since 2005
British Pharmacological Society
since 2006
Member of the School of Behavioral and Cognitive Neuroscience at the
University Groningen
Professional service and management
Institut für Pharmakologie, Universitätsklinikum Essen
since 1995
Radiation safety officer
since 1998
Project and team leader (research group: 2 technicians, 1 post-doc fellow, 1-2
Ph.D. students)
1999 - 2000
Coordinator of the reconstruction of the radiation safety laboratory in
cooperation with the Sicherheitstechnischer Dienst of the hospital
since 2001
Doctoral examination of graduate students
since 2001
Project leader of an S1-biohazard laboratory
since 2002
Project leader of an S2-biohazard laboratory
2002 - 2003
Coordinator of the installation of a radiation safety plus S2-biohazard
laboratory in cooperation with the Sicherheitstechnischer Dienst and the BauDezernat of the hospital (model project in the country Nordrhein-Westfalen,
Germany)
Medical Faculty of the University Duisburg-Essen
since 2002
Contribution to the Forschungstag of the faculty
- Supervision of oral and poster presentations of Ph.D. students
- Member of the evaluation committee
since 2003
Tutor in the University Lecturer Training Course "Lehren Lernen" (Teach the
Teachers), Medical Faculty of the University Duisburg-Essen in cooperation
with the Zentrum für Hochschuldidaktik und Qualitäts-entwicklung
since 2004
Coordinator of the Female Mentor Network "Meduse" at the Medical Faculty
of the University Duisburg-Essen, Foundation of the project MediMent
(Medizin Mentoring)
since 2004
Member of the Lenkungsgruppe of the project MediMent. Tandem supervision
of excellent female researchers
since 2004
Mentor in the project MediMent (Mentee: Dr. Heike Bruck)
since 2004
Member of the Zentrum für Medizinische Biotechnologie (ZMB) research
networking platform. Initiation of new collaborations (Prof. Dr. E. Gulbins,
Prof. Dr. B. Lefkau)
since 2004
Member of the Westdeutsches Tumorzentrum Essen eV (WTZE).
Development of new research accents
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Dr. Martina Schmidt
Professional activities elsewhere
since 2002
Member of the poster evaluation committee at the annual Spring Meetings of
the Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie
und Toxikologie, Johannes Gutenberg University, Mainz
Sept. 2004
Master class Graduate School of Behavioural and Cognitive Neurosciences
(BCN), University of Groningen
Meetings
since 1998
since 2000
Sept. 2005
July 2008
Organization of Institute Seminars with invited speakers, Institut für
Pharmakologie, Universitätsklinikum Essen.
Chairman and discussion leader of program sessions at the annual Spring
Meetings of the Deutsche Gesellschaft für Experimentelle und Klinische
Pharmakologie und Toxikologie, Johannes Gutenberg University, Mainz
Molecular Cardiology Seminar, AMC, The Netherlands
Regulation of cellular signaling by Tiam-1; Invited speakers:
Dr. John Collard, Div. Cell Biology, Netherlands Cancer Institute
Dr. Thomas Wieland, Institut für Pharmakologie und Toxikologie, University
of Heidelberg
EUPHAR 2008: Epac: A novel signaling factor in the pulmonary and
cardiovascular system; Organizer: Dr. Martina Schmidt, Invited speakers:
Dr. Johannes Bos, Utrecht, The Netherlands; Dr. Stephen Yarwood, Glasgow,
UK; Dr. Manueal Zaccolo, Padua, Italy, Dr. Martina Schmidt, Groningen, The
Netherlands
Invitated lectures international meetings
2007
5th International symposium on receptor mechanisms, signal transduction and
drug effects; Shizuoka, Japan
2009
Symposium G-protein targets Experimental biology meeting, New Orleans
Professional activities University of Groningen and Dutch societies
since 2007
Editorial Board of the “Nederlandse Vereniging voor Farmacologie”
2008 Editorial Board: Current Molecular Pharmacology
2008 Editorial Board of Groningen Research Institute for Asthma and COPD
2008 Member of the opleidings commissie farmacie at the University of Groningen
Collaborations
University Duisburg-Essen
Prof. Dr. Artur-Aron Weber, Pharmakologie: Signaling pathways in lymphoid cells
Prof. Dr. Ursula Rauen, Physiologische Chemie: Cold-induced apoptosis of the liver
Germany
PD Dr. Harald Genth, Toxikologie, MH Hannover: Bacterial toxins
PD Dr. Jörg Heller, Universitätsklinikum Bonn: Mechanisms of vascular hypocontractility by
portal hypertension
Prof. Dr. Bernd Nürnberg, Pharmakologie, Universität Tübingen: Role of PI 3-kinase in the
PLD response
Prof. Dr. Dieter Rosskopf, Pharmakologie, Universität Greifswald: PLC-and Epac siRNAs
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Dr. Martina Schmidt
Prof. Dr. Thomas Wieland, Pharmakologie & Toxikologie, Mannheim of the University
Heidelberg: Regulation and physiological importance of PLD signaling in cardiomyocytes.
Netherlands
Prof. Dr. Johannes Bos, Physiological Chemistry, Utrecht: Physiological role of Epac
signaling in whole animals
Dr. Maurice van den Hoff, Anatomy & Embryology, Amsterdam: Reprogramming of cardiac
fibroblasts into myocardial lineage
Prof. Dr. Martin Michel, Pharmacology & Pharmacotherapy, Amsterdam: Role of Epac and
PLD in vascular smooth muscle contraction
Prof. Dr. Ulrich Eisel, Molecular Neurobiology, Groningen: Pathways in the chronic
inflammatory disorders Alzheimer’s dementia and COPD
Prof. Dr. Rob Henning, Clinical Pharmacology, Groningen: Exploting nature’s tricks:
dissecting hibernation to limit organ damage
International
Prof. Dr. Li Han, Dept. Infection Control & Research, Beijing: Actin organization by cofilin
and PLD during bacterial and viral infection
Prof. Dr. Susumo Seino, Kobe, Japan: Epac-deficient mice models
Dr. Lonny Levin, Cornell, USA: Soluble adenylyl cyclclase and immune cells
Dr. Alan Smrcka, Rochester, USA: Phospholipase C- and COPD
Dr. Manuela Zaccolo, Glasgow, UK: Spatio-temporal cAMP signaling in the airways
Dr. Stephen Yarwood, Glasgow, UK: Inflammatory mediator and Epac
6
Scientific publications and patent(s)
International (refereed) journals IF = Impact factor
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
Schmidt, M., Varsányi, M., Thieleczek, R. & Heilmeyer Jr., L.M.G. (1993) Identification of a new 80 k
isoform of phosphatidylinositol 4-phosphate 5-kinase from bovine brain. FEBS Lett. 325, 201-204.
(IF=3.84)
Schmidt, M., Hüwe, S.M., Fasselt, B., Homann, D., Rümenapp, U., Sandmann, J. & Jakobs, K.H.
(1994) Mechanisms of phospholipase D stimulation by m3 muscarinic acetylcholine receptors.
Evidence for involvement of tyrosine phosphorylation. Eur. J. Biochem. 225, 667-675. (IF=3.26)
Wieland, T., Liedel, K., Kaldenberg-Stasch, S., Meyer zu Heringdorf, D., Schmidt, M. & Jakobs, K.H.
(1995) Analysis of receptor-G protein interactions in permeabilized cells. Naunyn-Schmiedeberg´s
Arch. Pharmacol. 351, 329-336. (IF=1.96)
van Koppen, C.J., Lenz, W., Nunes, J.P.L., Zhang, C., Schmidt, M. & Jakobs, K.H. (1995) The role of
membrane proximal threonine residues conserved among guanine-nucleotide-binding-protein-coupled
receptors in internalization of the m4 muscarinic acetylcholine receptor. Eur. J. Biochem. 234, 536-541.
(IF=3.26)
Schmidt, M., Fasselt, B., Rümenapp, U., Bienek, C., Wieland, T., van Koppen, C.J. & Jakobs, K.H.
(1995) Rapid and persistent desensitization of m3 muscarinic acetylcholine receptor-stimulated
phospholipase D. Concomitant sensitization of phospholipase C. J. Biol. Chem. 270, 19949-19956.
(IF=6.36)
Schmidt, M., Bienek, C., van Koppen, C.J., Michel, M.C. & Jakobs, K.H. (1995) Differential calcium
signalling by m2 and m3 muscarinic acetylcholine receptors in a single cell type. NaunynSchmiedeberg´s Arch. Pharmacol. 352, 469-476. (IF=1.96)
Rümenapp, U., Geiszt, M., Wahn, F., Schmidt, M. & Jakobs, K.H. (1995) Evidence for ADPribosylation-factor-mediated activation of phospholipase D by m3 muscarinic acetylcholine receptor.
Eur. J. Biochem. 234, 240-244. (IF=3.26)
Gehrmann, T., Vereb, G., Schmidt, M., Klix, D., Meyer, H.E., Varsányi, M. & Heilmeyer Jr., L.M.G.
(1996) Identification of a 200 kDa polypeptide as type 3 phosphatidylinositol 4-kinase from bovine
brain by partial protein and cDNA sequencing. Biochim. Biophys. Acta 1311, 53-63. (IF=3.48)
Schmidt, M., Rümenapp, U., Bienek, C., Keller, J., von Eichel-Streiber, C. & Jakobs, K.H. (1996)
Inhibition of receptor signaling to phospholipase D by Clostridium difficile toxin B. Role of Rho
proteins. J. Biol. Chem. 271, 2422-2426. (IF=6.36)
Schmidt, M., Bienek, C., Rümenapp, U., Zhang, C., Lümmen, G., Jakobs, K.H., Just, I., Aktories, K.,
Moos, M. & von Eichel-Streiber, C. (1996) A role for Rho in receptor- and G protein-stimulated
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[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25]
[26]
[27]
[28]
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Dr. Martina Schmidt
phospholipase C. Reduction in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxin B.
Naunyn-Schmiedeberg´s Arch. Pharmacol. 354, 87-94. (IF=1.96)
Zhang, C., Schmidt, M., von Eichel-Streiber, C. & Jakobs, K.H. (1996) Inhibition by toxin B of inositol
phosphate formation induced by G protein-coupled and tyrosine kinase receptors in N1E-115
neuroblastoma cells: Involvement of Rho proteins. Mol. Pharmacol. 50, 864-869. (IF=5.08)
Schmidt, M., Nehls, C., Rümenapp, U. & Jakobs, K.H. (1996) m3 Muscarinic receptor-induced and Gimediated heterologous potentiation of phospholipase C stimulation: Role of phosphoinositide synthesis.
Mol. Pharmacol. 50, 1038-1046. (IF=5.08)
Schmidt, M., Rümenapp, U., Nehls, C., Ott, S., Keller, J., von Eichel-Streiber, C. & Jakobs, K.H.
(1996) Restoration of Clostridium difficile toxin-B-inhibited phospholipase D by phosphatidylinositol
4,5-bisphosphate. Eur. J. Biochem. 240, 707-712. (IF=3.26)
Rümenapp, U., Schmidt, M., Wahn, F., Tapp, E., Grannass, A. & Jakobs, K.H. (1997) Characteristics
of protein-kinase-C- and ADP-ribosylation-factor-stimulated phospholipase D activities in human
embryonic kidney cells. Eur. J. Biochem. 248, 407-414. (IF=3.26)
Keller, J., Schmidt, M., Hussein, B., Rümenapp, U. & Jakobs, K.H. (1997) Muscarinic receptorstimulated cytosol-membrane translocation of RhoA. FEBS Lett. 403, 299-302. (IF=3.84)
Lümmen, G., Virchow, S., Rümenapp, U., Schmidt, M., Wieland, T., Otto, T., Rübben, H. & Jakobs,
K.H. (1997) Identification of G protein-coupled receptors potently stimulating migration of human
transitional-cell carcinoma cells. Naunyn-Schmiedeberg´s Arch. Pharmacol. 356, 769-776. (IF=1.96)
Schmidt, M., Lohmann, B., Hammer, K., Haupenthal, S., Voß, M., Nehls, C. & Jakobs, K.H. (1998)
Gi- and protein kinase C-mediated heterologous potentiation of phospholipase C signaling by G proteincoupled receptors. Mol. Pharmacol. 53, 1139-1148. (IF=5.08)
Rümenapp, U., Schmidt, M., Olesch, S., Ott, S., von Eichel-Streiber, C. & Jakobs, K.H. (1998)
Tyrosine-phosphorylation-dependent and Rho-protein-mediated control of cellular phosphatidylinositol
4,5-bisphosphate levels. Biochem. J. 334, 625-631. (IF=4.28)
Schmidt, M., Voß, M., Thiel, M., Bauer, B., Grannaß, A., Tapp, E., Cool, R.H., de Gunzburg, J., von
Eichel-Streiber, C. & Jakobs, K.H. (1998) Specific inhibition of phorbol ester-stimulated phospholipase
D by Clostridium sordellii lethal toxin and Clostridium difficile toxin B-1470 in HEK-293 cells.
Restoration by Ral GTPases. J. Biol. Chem. 273, 7413-7422. (IF=6.36)
Meyer zu Heringdorf, D., Lass, H., Alemany, R., Laser, K.T., Neumann, E., Zhang, C., Schmidt, M.,
Rauen, U., Jakobs, K.H. & van Koppen, C.J. (1998) Sphingosine kinase-mediated Ca2+ signalling by Gprotein-coupled receptors. EMBO J. 17, 2830-2837. (IF=10.49)
Vögler, O., Krummenerl, P., Schmidt, M., Jakobs, K.H. & van Koppen, C.J. (1999) RhoA-sensitive
trafficking of muscarinic acetylcholine receptors. J. Pharmacol. Exp. Ther. 288, 36-42. (IF=4.34)
*Schürmann, A., *Schmidt, M., Asmus, M., Bayer, S., Fliegert, F., Koling, S., Maßmann, S., Schilf, C.,
Subauste, M.C., Voß, M., Jakobs, K.H. & Joost, H.-G. (1999) The ADP-ribosylation factor (ARF)related GTPase ARF-related protein binds to the ARF-specific guanine nucleotide exchange factor
cytohesin and inhibits the ARF-dependent activation of phospholipase D. J. Biol. Chem. 274, 97449751. *Equal contribution. (IF=6.36)
Schmidt, M., Voß, M., Oude Weernink, P.A., Wetzel, J., Amano, M., Kaibuchi, K. & Jakobs, K.H.
(1999) A role for Rho-kinase in Rho-controlled phospholipase D stimulation by the m3 muscarinic
acetylcholine receptor. J. Biol. Chem. 274, 14648-14654. (IF=6.36)
Vögler, O., Nolte, B., Voss, M., Schmidt, M., Jakobs, K.H. & van Koppen, C.J. (1999) Regulation of
muscarinic acetylcholine receptor sequestration and function by -arrestin. J. Biol. Chem. 274, 1233312338. (IF=6.36)
Meyer zu Heringdorf, D., Lass, H., Kuchar, I., Alemany, R., Guo, Y., Schmidt, M. & Jakobs, K.H.
(1999) Role of sphingosine kinase in Ca2+ signalling by epidermal growth factor receptor. FEBS Lett.
461, 217-222. (IF=3.84)
Keffel, S., Schmidt, M., Bischoff, A. & Michel, M.C. (1999) Neuropeptide-Y stimulation of
extracellular signal-regulated kinases in human erythroleukemia cells. J. Pharmacol. Exp. Ther. 291,
1172-1178. (IF=4.34)
Voß, M., Oude Weernink, P.A., Haupenthal, S., Möller, U., Cool, R.H., Bauer, B., Camonis, J.H.,
Jakobs, K.H. & Schmidt, M. (1999) Phospholipase D stimulation by receptor tyrosine kinases mediated
by protein kinase C and a Ras/Ral signaling cascade. J. Biol. Chem. 274, 34691-34698. (IF=6.36)
Oude Weernink, P.A., Schulte, P., Guo, Y., Wetzel, J., Amano, M., Kaibuchi, K., Haverland, S., Voß,
M., Schmidt, M., Mayr, G.W. & Jakobs, K.H. (2000) Stimulation of phosphatidyl-inositol-4-phosphate
5-kinase by Rho-kinase. J. Biol. Chem. 275, 10168-10174. (IF=6.36)
Oude Weernink, P.A., Guo, Y., Zhang, C., Schmidt, M., von Eichel-Streiber, C. & Jakobs, K.H. (2000)
Control of cellular phosphatidylinositol 4,5-bisphosphate levels by adhesion signals and Rho GTPases
in NIH 3T3 fibroblasts. Eur. J. Biochem. 267, 5237-5246. (IF=3.26)
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Dr. Martina Schmidt
[30]
Schmidt, M., Frings, M., Mono, M.-L., Guo, Y., Oude Weernink, P.A., Evellin, S., Han, L. & Jakobs,
K.H. (2000) G protein-coupled receptor-induced sensitization of phospholipase C stimulation by
receptor tyrosine kinases. J. Biol. Chem. 275, 32603-32610. (IF=6.36)
Rümenapp, U., Asmus, M., Schablowski, H., Woznicki, M., Han, L., Jakobs, K.H., Fahimi-Vahid, M.,
Michalek, C., Wieland, T. & Schmidt, M. (2001) The M3 muscarinic acetylcholine receptor expressed
in HEK-293 cells signals to phospholipase D via G12 but not Gq type G proteins. Regulators of G
proteins as tools to dissect pertussis toxin-resistant G proteins in receptor-effector coupling. J. Biol.
Chem. 276, 2474-2479. (IF=6.36)
Schmidt, M., Evellin, S., Oude Weernink, P.A., vom Dorp, F., Rehmann, H., Lomasney, J.W. &
Jakobs, K.H. (2001) A new phospholipase-C-calcium signalling pathway mediated by cyclic AMP and
a Rap GTPase. Nature Cell Biol. 3, 1020-1024. (IF=20.65)
Evellin, S., Nolte, J., Tysack, K., vom Dorp, F., Thiel, M., Oude Weernink, P.A., Jakobs, K. H., Webb,
E., Lomasney, J.W. & Schmidt, M. (2002) Stimulation of phospholipase C- by the M3 muscarinic
acetycholine receptor mediated by cyclic AMP and the GTPase Rap2B. J. Biol. Chem. 277, 1680516813. (IF=6.36)
Wilde, C., Barth, H., Sehr, P., Han, L., Schmidt, M., Just, I. & Aktories, K. (2002) Interaction of the
Rho-ADP-ribosylating C3 exoenzyme with RalA. J. Biol. Chem. 277, 14771-14776. (IF=6.36)
Fahimi-Vahid, M., Gosau, N., Michalek, C., Han, L., Jakobs, K.H., Schmidt, M., Roberts, N., Avkiran,
M. & Wieland, T. (2002) Distinct signaling pathways mediate cardiomyocyte phospholipase D
stimulation by endothelin-1 and thrombin. J. Mol. Cell Cardiol. 34, 441-453. (IF=4.20)
Gosau, N., Fahimi-Vahid, M., Michalek, C., Schmidt, M. & Wieland, T. (2002) Signalling components
involved in the coupling of 1-adrenoceptors to phospholipase D in neonatal rat cardiac myocytes.
Naunyn-Schmiedeberg’s Arch. Pharmacol. 365, 468-476. (IF=1.96)
Fetscher, C., Fleichmann, M., Schmidt, M., Krege, S. & Michel, M.C. (2002) M3 muscarinic receptors
mediate contraction of human urinary bladder. Br. J. Pharmacol. 136, 641-644. (IF=3.33)
Heneweer, C., Kruse, L.H., Kindhäuser, F., Schmidt, M., Jakobs, K.H., Denker, H.-W., Thie, M.
(2002) Adhesiveness of human uterine epithelial RL95-2 cells for trophoblast: Rho protein regulation.
Mol. Hum. Reprod. 8, 1014-1022. (IF=3.07)
Genth, H., Schmidt, M., Gerhard, R., Aktories, K. & Just, I. (2003) Activation of phospholipase D1 by
ADP-ribosylated RhoA. Biochem. Biophys. Res. Commun. 302, 127-132. (IF=2.90)
Stope, M.B., kunkel, C., Kories, C., Schmidt, M. & Michel, M.C. (2003) Differential agonist-induced
regulation of human M2 and M3 muscarinic receptors. Biochem. Pharmacol. 66, 2099-2105. (IF=3.44)
Oude Weernink, P.A., Meletiadis, K., Hommeltenberg, S., Hinz, M., Ishihara, H., Schmidt, M. &
Jakobs, K.H. (2004) Activation of type I phosphatidylinositol-4-phosphate 5-kinase isoforms by the
Rho GTPases, RhoA, Rac1, and Cdc42. J. Biol. Chem. 279, 7840-7849. (IF=6.36)
Lutz, S., Freichel-Blomquist, A., Rümenapp, U., Schmidt, M., Jakobs, K.H. & Wieland, T. (2004)
p63RhoGEF and GEFT are Rho-specific guanine nucleotide exchange factors encoded by the same
gene. Naunyn-Schmiedeberg’s Arch. Pharmacol. 369, 540-546. (IF=1.96)
vom Dorp, F., Sari, A.Y., Sanders, H., Keiper, M., Oude Weernink, P.A., Jakobs, K.H. & Schmidt, M.
(2004) Inhibition of phospholipase C- by Gi-coupled receptors. Cell. Signal. 16, 921-928. (IF=4.74)
Stope, M.B., vom Dorp, F., Szatkowski, D., Böhm, A., Keiper, M., Nolte, J., Oude Weernink, P.A.,
Rosskopf, D., Evellin, S., Jakobs, K.H. & Schmidt, M. (2004) Rap2B-dependent stimulation of
phospholipase C-by epidermal growth factor receptor mediated by c-Src phosphorylation of
RasGRP3. Mol. Cell. Biol. 24, 4664-4676. (IF=7.82)
Keiper, M., Stope, M.B., Szatkowski, D., Böhm, A., Tysack, K., vom Dorp, F., Saur, O., Oude
Weernink, P.A., Evellin, S., Jakobs, K.H. & Schmidt, M. (2004) Epac- and Ca2+-controlled activation
of Ras and extracellular signal-regulated kinases by Gs-coupled receptors. J. Biol. Chem. 279, 4649746508. (IF=6.36)
Lutz, S., Freichel-Blomquist, A., Yang, Y., Rümenapp, U., Jakobs, K.H., Schmidt, M. & Wieland, T.
(2005) The guanine nucleotide exchange factor p63RhoGEF  a specific link between Gq/11-coupled
receptor signaling and RhoA. J. Biol. Chem. 280, 11134-11139. (IF=6.36)
Hennenberg, M., Biecker, E., Trebicka, J., Jochem, K., Zhou, Q., Schmidt, M., Jakobs, K.H.,
Sauerbruch, T. & Heller, J. (2005) Defective RhoA/Rho-kinase signaling contributes to vascular
hypocontractility and vasodilation in cirrhotic rats. Gastroenterology 130, 838-854. (IF=13.09)
López de Jesús, M., Stope, M.B., Oude Weernink, P.A., Börgermann, C., Ananaba, V.N., Michel, M.C.,
Jakobs, K.H. & Schmidt, M. (2006) Cyclic AMP-dependent and Epac-mediated activation of R-Ras by
G proteins-coupled receptors. Involvement of R-Ras in receptor-mediated stimulation of phospholipase
D. J. Biol. Chem. J. Biol. Chem. 281, 21837-21847. (IF=6.36)
Vogt, A., Lutz, S., Rümenapp, U., Han, L., Jakobs, K.H., Schmidt, M. & Wieland, T. (2007)
Regulators of G protein signalling 3 redirects prototypical Gi-coupled receptors from Rac to Rho
activation. Cell. Signal. 19, 1229-1237. (IF=4.74)
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[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
[47]
[48]
[49]
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Dr. Martina Schmidt
[50]
Barendrecht, M.M., Mulders, A.C.M., van der Poel, H., van den Hoff, M., Schmidt, M. & Michel,
M.C. (2007) Role of transforming growth factor  in rat bladder smooth muscle cell proliferation. J.
Pharmacol. Exp. Ther. 322, 117-122. (IF=4.34)
Gkoumassi, E., Dröge, M.J., Dekkers, B.G.J., Elzinga, C.R.S., Schmidt, M., Meurs, H., Zaagsma, J. &
Nelemans, S.A. (2007) Virodhamine and CP55,940 modulate cAMP production and IL-8 release in
human bronchial epithelial cells. Br. J. Pharmacol. 151, 1041-1048 (IF=3.33)
Han, L., Stope, M.B., López de Jesús, M., Oude Weernink, P.A., Urban, M., Wieland, T., Rosskopf, D.,
Jakobs, K.H. & Schmidt, M. (2007) Phospho-cofilin directly interacts with and stimulates receptorcontrolled phospholipase D1. EMBO J. 26, 4189-4202. (IF=10.46)
Nunes, R.O., Schmidt, M., Dueck, G., Baarsma, H., Halayko, A.J., Kerstjens, H.A., Meurs, H., Gosens,
R. (2008) The GSK-3/-catenin signaling axis in airway smooth muscle: Role in mitogenic signaling.
Am. J. Physiol. Lung Cell Mol. Physiol. 294, 1110-1118.
Nijholt, I., Dolga, A.M., Vieth, T., Ostroveanu, A., de Bruyn, M., Luiten, P.G.M., Schmidt, M. & Eisel,
U.L.M. (2008) Neuronal AKAP150 coordinates PKA and Epac mediated PKB/Akt phosphorylation.
Cell. Signal .20, 1715-1724.
Grandoch, M., Oude Weernink, P.A., Weber, A.-A., Kajobs, K.H. & Schmidt, M. (2009) B cell
receptor-induced growth arrest and apoptosis in WEHI-231 cells immature B lymphoma cells involve
cyclic AMP and Epac proteins. Cell. Signal. 21, 609-621.
Gkoumassi, E., Dekkers, B.G.J., Dröge, M.J., Elzinga, C.R.S., Hasenbosch, R.E., Meurs, H. S.A.
Nelemans, Schmidt, M. & Zaagsma, J. (2009) Virodhamine and CP55,940 modulate cAMP production
and IL-8 release in human bronchial epithelial cells. Naunyn-Schmiedeberg’s Arch. Pharmacol., DOI
10.1007/s00210-009-0406-z
Grandoch, M., Bujok, V., Fleckenstein, D., Schmidt, M., Fischer, J.W. & Weber, A.-A. (2009) Epac
inhibits apoptosis of human leukocytes. J. Leuk. Biol., in press.
[51]
[52]
[53]
[54]
[55]
[56]
[57]
Books
[1]
[2]
[3]
[4]
Vereb, G., Schmidt, M., Klix, D., Varsányi, M. & Heilmeyer Jr., L.M.G. (1992) Isolation and
characterization of phosphatidylinositol 4-kinase isozymes from bovine brain. Springer-Verlag NATO
ASI Series Vol. 76, pp. 167-171.
Schmidt, M., Vereb, G., Varsányi, M., Klix, D., Dreefs, C.E. & Heilmeyer Jr., L.M.G. (1992)
Renaturation of phosphatidylinositol 4- and phosphatidylinositol 4-phosphate 5'-kinases following
polyacrylamide gelelelectrophoresis in presence of SDS. Studies on their substrate binding requirements
using synthetic substrate analogues. Springer-Verlag NATO ASI Series Vol. 76, pp. 197-200.
Schmidt, M., Rümenapp, U., Zhang, C., Keller, J., Lohmann, B. & Jakobs, K.H. (1997) Receptor
regulation of phospholipases C and D. Springer-Verlag NATO ASI Series Vol. 101, pp. 199-209.
Schmidt, M., Oude Weernink, P.A., vom Dorp, F., Stope, M.B. & Jakobs, K.H. (2004) Mammalian
phospholipase C. Advances in Molecular and Cell Biology (van der Vusse GJ ed) Vol 33, Lipobiology
pp. 433-453, Elsevier Science, Amsterdam.
Review articles
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[9]
[10]
Rümenapp, U., Schmidt, M., Geiszt, M. & Jakobs, K.H. (1996) Participation of small GTP-binding
proteins in m3 muscarinic acetylcholine receptor signalling to phospholipase D and C. Prog. Brain Res.
Vol. 109, 209-216.
Schmidt, M., Rümenapp, U., Keller, J., Lohmann, B. & Jakobs, K.H. (1997) Regulation of
phospholipase C and D activities by small molecular weight G proteins and muscarinic receptors. Life
Sci. 60, 1093-1100.
Oude Weernink, P.A., Schmidt, M. & Jakobs, K.H. (2004) Regulation and cellular roles of
phosphoinositide 5-kinases. Eur. J. Pharmacol., 500, 87-99.
Peters, S.L.M., Schmidt, M. & Michel, M.C. (2006) Rho kinase: a target for treating urinary
incontinence. Trends Pharmacol. Sci. 27, 492-497.
Oude Weernink, P.A., Han, L., Jakobs, K.H. & Schmidt, M. (2006) Dynamic phospholipid signaling
by G protein-coupled receptors. Biochim. Biophys. Acta. 1768, 888-900.
Schmidt, M., Sand, C., Jakobs, K.H., Michel, M.C. & Oude Weernink, P.A. (2007) Epac and the
cardiovascular system. Curr. Opin. Pharmacol. 7, 193-200.
Oude Weernink, P.A., López de Jesús, M. & Schmidt, M. (2007) Phospholipase D signaling:
orchestration by PIP2 and small GTPases. Naunyn-Schmiedeberg’s Arch. Pharmacol. 374, 399-411.
Schaafsma, D., Roscioni, S.S., Meurs, H. & Schmidt, M. (2008) Monomeric G proteins as signal
transducers in airway (patho)physiology. Cell. Signal. 20, 1705-1714.
Gosens, R., Roscioni, S.S., Dekkers, B.G., Pera, T., Schmidt, M., Schaafsma, D., Zaagsma, J., Meurs,
H. (2008) Pharmacology of airway smooth muscle proliferation. Eur. J. Pharmacol. 585, 385-397.
Gosens, R., Meurs, H., Schmidt, M. (2008) The GSK-3/beta-catenin axis in smooth muscle and its
relationship with remodelling. Naunyn-Schmiedeberg’s Arch. Pharmacol. 378, 345-357185-191
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Dr. Martina Schmidt
[11]
Roscioni, S.S., Elzinga, C.R.S. & Schmidt, M. (2008) Epac: effectors and biological functions.
Naunyn-Schmiedeberg’s Arch. Pharmacol. 377, 345-357.
M. Grandoch, Roscioni, S.S. & Schmidt, M. (2009) Epac: novel cAMP mediators in inflammatory
pulmonary and neuronal dysfunction. Brit. J. Pharmacol., in revision.
[12]
Original manuscripts submitted/revision
[1]
Gosens, R., Barsma, H.A., Heijink, I.H., Halayko, A.J., Meurs, H. & Schmidt, M. De novo synthesis of
-catenin via H-Ras and MEK regulates airway smooth muscle growth. FASEB J.
Roscioni, S.S., Kistemaker, L.E.M., Menzen, M., Elzinga, C.R.S., Gosens, R., Halayko, A.J., Meurs, H.
& Schmidt, M. PKA and Epac cooperate to augment bradykinin-induced interleukin-8 release from
human airway smooth muscle. Resp. Res.
Sand, C., Börgermann, C., Oude Weernink, P.A., Mahlke, Y., Schwindenhammer, B., Weber, A.-A., &
Schmidt, M. 8-pCPT-conjugated cyclic AMP analogs exert thromboxane receptor antagonistic
properties. Biochem. Pharmacol.
Ostroveanu, A., van der Zee, E., Eisle, U.L.M., Schmidt, M. & Nijholt, I. Exchange protein directly
activated by cyclic AMP2 (Epac2) plays a specific and time-limited role in memory retrieval.
Hippocampus, in revision.
van Wijk, B., van den Berg, G., Abu-Issa, R., van der Velden, S., Schmidt, M., Ruijter, J.M., Kirby,
M.L., Moorman, A.F.M. & van den Hoff, M.J.B. Epicardial cells separate from the myocardial lineage
under influence of FGF-signaling via Mek1/2. Cir. Res., in revision.
[2]
[3]
[4]
[5]
Patent: Nijholt, I.M., Schmidt, M. (2008) "Modulation of memory function"; P85114US00
6
Acquisition of 2nd and 3rd-stream funding
1996
1998
1998
1999
1999
2001
2002
2003
2003
2004
Deutsche Forschungsgemeinschaft, project Regulation der Phospholipase D durch
Rezeptoren und GTPasen. 2 Ph.D. positions (BAT IIa/2) plus DM 180.000 for 3 years.
Deutsche Forschungsgemeinschaft, project Rezeptor-induzierte Langzeit-Potenzierung
der Phospholipase C-Stimulation. 1 Ph.D. position (BAT IIa/2), 1 technician (BAT
Vc) plus DM 105.000 for 3 years.
Recruitment of Ph.D. stipends from the Interne Forschungsförderung Essen. Up to
now: 15 positions for medical students plus € 5.000 per project.
Interne Forschungsförderung Essen, project Regulation der PIP2-Synthese durch Rho,
Rho-kinase und Rezeptoren. 2 positions for medical students plus DM 30.000 for 1
year.
Deutsche Forschungsgemeinschaft, project Regulation der Phospholipase D durch
Rezeptoren und GTPasen. 2 Ph.D. positions (2 BAT IIa/2), 1 technician (BAT Vc)
plus DM 180.000 for 3 years.
Interne Forschungsförderung Essen, project Charakterisierung eines neuen
Signaltransduktionsweges von Membranrezeptoren zur Phospholipase C. 2 positions
for medical students plus DM 38.000 for 1 year.
Deutsche Forschungsgemeinschaft, project Rezeptor-induzierte Langzeit-Potenzierung
der Phospholipase C-Stimulation. 1 Post-doc position (BAT IIa), 1 technician (BAT
Vb) plus € 61.355 for 3 years.
Fonds der Chemischen Industrie im Verband der Chemischen Industrie eV, € 3.000
plus travel expenses.
Interne Forschungsförderung Essen, project Aktivierung von Phospholipasen in
Lymphozyten - Funktionelle Analysen nach systematischem RNA-Silencing. 2
positions for medical students plus € 19.717 for 1 year.
Interne Forschungsförderung Essen, project Physiologische Rolle von Epac und
Phospholipase C- im kardiovaskulären System. € 12.000 for 1 year.
Page 10
2004
2005
2005
2006
2006
2006
2006
2008
2008
2008
7
Dr. Martina Schmidt
Post-doctoral fellowship for Dr. Maider López de Jesús from the Basque Goverment.
€ 52.000 for 2 years.
Forschungsstipendium, Deutsche Forschungsgemeinschaft, project Physiologische
Rolle von Epac-Proteinen im kardiovaskulären System. € 54.552 for 2 years.
Deutsche Forschungsgemeinschaft, project Mechanismen der vaskulären
Hypokontraktilität bei portaler Hypertension. Participant in the grant application of
Dr. Jörg Heller, Universitätsklinikum Bonn. 1 Ph.D. position (BAT IIa/2) plus €
40.000 for 2 years.
Deutsche Forschungsgemeinschaft, project Untersuchungen zum Mechanismus der
kälteinduzierten Apoptose. Participant in the grant application of Dr. Ursula Rauen,
Universitätsklinikum Essen (RA 960/1-3). 1 Ph.D. position (BAT IIa/2), 1 technician
(BAT Vb) plus € 48.000 for 3 years.
Rosalind Franklin Fellowship, start-up fund € 200.000
Transfer of € 150.000 to Groningen. Deutsche Forschungsgemeinschaft, project
Rezeptor-induzierte Langzeit-Potenzierung der Phospholipase C-Stimulation. 1 Postdoc position (BAT IIa), 1 technician (BAT Vb).
Ubbo Emmius Scholarship, University of Groningen. Ph.D. position for 4 years.
International Research Training Group GRK 880-3 Mannheim-Heidelberg-Groningen,
Vascular medicine, project - (Patho)physiological role of NO/cGMP-induced
RhoGEF17 activation in the vasculature. Principal Investigator with Dr. Susanne
Lutz, Depart. Experimental & Clinical Pharmacology and Toxicology, Unversity of
Heidelberg, Germany. 2 Ph.D. positions plus € 40.000 for 2 years.
Ubbo Emmius Scholarship, University of Groningen, Ph.D. position for 4 years.
Nederlands Astma Fonds, project The novel cAMP effector Epac: new avenues in the
treatment of inflammation, tissue remodeling and airway narrowing in COPD. €
250.974 for 4 years, 1 Ph.D. position.
Teaching
Professionalization and didactic schooling attended

University Lecturer Training Course “Lehren Lernen” (Teach the Teachers), Advanced Training
for University Teaching, Medical Faculty of the University Duisburg-Essen in cooperation with
the Zentrum für Hochschuldidaktik und Qualitätsentwicklung:
- Basic course Fundamental Theoretical Knowledge and Practical Competence in
University Teaching (19/20.10.2001 and 04/05.04.2003)
- Sequel Unit 1 (04.07.2003): „Lehrveranstaltungen planen“
- Sequel Unit 2 (12.12.2003): „ Rhetorik, Präsentation, Einsatz von Medien“

Seminar (27/28.05.2004): „Personalführung und Konfliktmanagement“, Dr. C. Färber

Seminar (01.05.2004): „Potenzialanalyse und Laufbahnplanung“, Dr. C. Färber
Undergraduate teaching given
Institut für Physiologische Chemie, Ruhr-University Bochum

Practical courses and oral examinations in Physiological Chemistry for medical students (1989 1992)
Page 11
Dr. Martina Schmidt
Institut für Pharmakologie, Faculty of Medicine, University Duisburg-Essen
Teaching of medical students:

Seminars in General and Systemic Pharmacology and Toxicology (1993-2005)
- Adrenergic system and pharmacology of asthma bronchiale; Cholinergic agents, skeletal
muscle relaxants and histamine; Vasodilators and antihypertensives; Treatment of heart
failure and antiarrhythmic drugs; Haemostasis, thrombosis and diuretics; Antibiotics;
- Opioid and non-opioid analgesic drugs; Thyroid agents, insulin and oral hypoglycemic
agents; Corticosteroids and sex hormones; Antidepressants, sedatives & antipsychotic drugs.

Lectures in General Pharmacology and Toxicology (1999-2005)
- Antiviral and antifungal agents; Immunosuppressive agents; Pharmacokinetics: Drug
absorption, distribution, and elimination; Drug metabolism.

Problem-based Learning (2003-2005)
With the lecturer as mentor, students in small groups of 10 work out independently selected
topics in pharmacology and toxicology, after having presented and discussed representative
patient case studies.

Examination of undergraduate students (2004-2005)
Responsible for the entire organization and execution of the course General and Systemic
Pharmacology and Toxicology, including programming, composing and judging the
examination-papers.
Faculty of Medicine, University Duisburg-Essen

Doctoral examination of graduate students (2001- )

Tutor in the University Lecturer Training Course "Lehren Lernen" (2003-2005)

Coordinator of the University Female Mentor Network "Meduse" (2004- )
University of Groningen

Bachelor Postpropedeuse Farmacie / Farmaceutische Wetenschappen

Flexibel Bacheloropleiding Levenswetenschappen (propedeuse)
(Students of Biology, Pharmacy, Medical Biology, Medicine)

Algemene Farmacologie I (Introduction Physiology & Pharmacology, level 1)

Algemene Farmacologie II (Introduction Physiology & Pharmacology, level 2)

Course coordination & student lectures (5 ECTS)

Flexible Bacheloropleiding Levenswetenschappen (post-propedeuse)

Receptorpharmakologie

Course coordination & student lectures (5ECTS)

Master Farmacie / Farmaceutische Wetenschappen

Geneesmiddelgroepen: Tractus Circulatorius

Physiology & Pharmacology: Cardiovascular system, kidney, blood

Course coordination & student lectures (5 ECTS)

Caput Moleculaire Farmacologie (Master Farmacie)

Course coordination & student lectures (3 ECTS)

Participatie in Communicatie en Orientatie (Farmacologie)

Begeleiding Practicum Moleculaire Farmacologie

Begeleiding Hoofd- en Bijvakonderzoek (Bachelor & Master)

BCN International Master Course

Participatie in Genes, Brain, and Brain Functions
Page 12
Dr. Martina Schmidt
% time teaching
Duties and responsibilities in Teaching required about 30 % of my working hours.
Ph.D. Supervisor
Institut für Pharmakologie, Graduation University Duisburg-Essen, Faculty of Medicine
Dr. med. is about equivalent to a Dutch undergraduate master project
[1]
[2]
[3]
[4]
[5]
[6]
[7]
[8]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
Dr. med. Birgit Maria Fasselt (1993-1994) November 1995. Judgement: magna cum laude.
Dr. med. Yuanjian Guo (1997-1999) May 1999. Judgement: magna cum laude.
Dr. med. Markus Frings (1997-1998) March 2001. Judgement: magna cum laude.
Dr. med. Stephan Haupenthal (1997-1998) September 2001. Judgement: magna cum laude.
Dr. med. Kerstin Hammer (1997-1998) October 2001. Judgement: magna cum laude.
Dr. med. Ursula Möller (1997-1998) November 2001. Judgement: magna cum laude.
Dr. med. Christoph Nehls (1995) January 2002. Judgement: magna cum laude.
Dr. med. Christine Bienek (1994-1995) May 2002. Judgement: cum laude.
Dr. med. Marie-Luise Mono (1999) November 2002. Judgement: magna cum laude.
Dr. med. Eva Tapp (1997) November 2002. Judgement: magna cum laude.
Dr. med. Silke Bayer (1998) November 2002. Judgement: magna cum laude.
Dr. med. Sibylle Eicken (1999-2001) May 2003. Judgement: cum laude.
Dr. med. Christina Rother (1998-1999) May 2003. Judgement: magna cum laude.
Dr. med. Karina Tysack (2001-2002) October 2004. Judgement: magna cum laude.
Dr. med. Jan Nolte (2001-2002) October 2004. Judgement: magna cum laude.
Dr. med. Felix Kindhäuser (2000-2001) October 2004. Judgement: cum laude.
Dr. med. Melanie Asmus (1998) May 2005. Judgement: magna cum laude.
Dr. med. Anja Böhm (2002) November 2005. Judgement: magna cum laude.
Dr. med. Patrizia Caracciola (1999-2000) December 2005. Judgement: magna cum laude.
Dr. med. Ayse Y. Sari (2001-2002) May 2006. Judgement: magna cum laude.
Dr. med. Daniel Szatkowski (2002) November 2006. Stipendiary of the Studienstiftung des
deutschen Volkes. Judgement: magna cum laude.
[23] Dr. med. Bernhard Limper (2008) Ocotber 2008, Jugdgement: cum laude.
[24] Dr. med. Martina Urban (2009) March 2009, Judgement: magna cum laude.
Institut für Pharmakologie, Graduation University Duisburg-Essen,
Departments of Biology, Chemistry and Pharmacy
Dr. rer. nat. is equivalent to a Dutch graduate thesis
[1]
[2]
[3]
[4]
[5]
Dr. rer. nat. Ulrich Rümenapp (1993-1996) December 1996. Judgement: summa cum laude.
Fritz-Külz-Preis für Experimentelle Pharmakologie of the Deutsche Gesellschaft für
Experimentelle und Klinische Pharmakologie und Toxikologie.
Dr. rer. nat. Matthias Voß (1996-2000) September 2000. Judgement: magna cum laude.
Dr. rer. nat. Sandrine Evellin (1999-2003) January 2003. Judgement: magna cum laude.
Dr. rer. nat. Li Han (2000-2003) March 2003. Judgement: magna cum laude.
Dr. rer. nat. Melanie Keiper (2002-2005) March 2005. Judgement: magna cum laude.
Ph.D. External Examiner
Faculty of Medicine, University Duisburg-Essen
[1] Dr. med. Norman Putzki (2002) Judgement: magna cum laude.
[2] Dr. med. Andrea Waβmuth (2002) Judgement: cum laude.
[3] Dr. med. Bertrand Prévôt (2003) Judgement: magna cum laude.
[4] Dr. med. Mirabutaleb Samimi (2003) Judgement: cum laude.
[5] Dr. med. Thomas-Heinrich Vockel (2003) Judgement: cum laude.
[6] Dr. med. Dörthe Zupancic (2003) Judgement: cum laude.
[7] Dr. med. Petronela Nemesszeghyova (2003) Judgement: magna cum laude.
[8] Dr. med. Anne Flörcken (2004) Judgement: magna cum laude.
Page 13
[9]
Dr. Martina Schmidt
Dr. med. Julia Fee Landscheidt (2004) Judgement: magna cum laude.
Elsewhere
[1] Dr. rer. nat. Stéphanie Boutillier (2002) University of Strasbourg. Judgement: magna cum laude.
[2] Dr. Angela Hommel (2007) Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke.
Judgement: magna cum laude.
Ph.D. Supervisor-University Groningen
[1] Dr. Mark Boterman (2006) Groningen. Molecular Pharmacology. Judgement: cum laude.
[2] Dr. Harm Maarsingh (2006) Groningen. Molecular Pharmacology. Judgement: cum laude.
[3] Dr. Dedmer Schaafsma (2007) Groningen. Molecular Pharmacology. Judgement: cum laude.
[4] Dr. Martin Hennenberg (2007) Groningen. Molecular Pharmacology. Judgement: cum laude.
[5] Dr. Effimia Gkoumassi (2007) Groningen. Molecular Pharmacology. Judgement: cum laude.
[6] Dr. Amalia M. Dolga (2008) Groningen. Judgement: cum laude.
[7] cand. Dr. Sarah Roscioni (2006-) Airway smooth muscle transition and its impact on the
progession of COPD.
[8] cand. Dr. Fatemeh Talaei (2008) Epac: A key role in hibernation?
Supervision of Postdoctoral fellows and guest researchers
[1] Dr. Frank vom Dorp (2001-2003)
[2] Dr. Christoph Börgermann (2004-2005)
[3] Dr. Maider López de Jesús (2004-). Stipendiary of the Basque Government.
[4] Dr. Christina Michalek (2002)
[5] Dr. Peter Hein (2002)
[6] Dr. Carola Heneweer (2002-2004)
[7] Dr. Christoph Altmann (2003)
[8] Dr. Martin Hennenberg (2004-)
[9] Dr. Harm Maarsingh (2006-)
[10] Dr. Reinoud Gosens (2006-)
[11] Dr. Ingrid Nijholt (2006-)
9
Research concept
My scientific record verifies our achievements and reputation in the molecular regulation of
phospholipases, G proteins, and lipid and protein kinases by membrane receptors, and the discovery of
novel signaling cascades in various cellular systems. It is becoming increasingly clear that signaling
pathways are executed after clustering of molecular partners in defined subcellular compartments
(signalosomes), that enables cells to exert highly specialized tasks. Actually, our goal for the future is
to unravel the organization of the recently discovered signaling components within functional units by
biochemical, molecular and cell biological methods. A second goal will be to further define how these
novel pathways regulate physiological processes in cell, tissue and organ systems. We have directed
our attention to chronic inflammatory disorders, as evidence exist for a role of our signaling
components (Epac, PLD) in vascular smooth muscle cells, neuronal cells, immune cells as well as
cardiomyocytes and airway smooth muscle cells. Many devastating diseases, e.g. cancer, type-II
diabetes mellitus, Alzheimers’s dementia, cardiovascular and airway diseases (heart failure, cardiac
arrhythmia, developmental defects, asthma and COPD) are associated with defective or derailed
signaling processes, and research into the control of these processes clearly is of great public and
social importance as well. The proposed goals clearly demand a multidisciplinary proceeding, and
continuing and new collaborations with local, national and international groups will be increasingly
important to finish successful projects and to continue the strong and high-ranking publication output.
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Dr. Martina Schmidt

Regulation of phospholipase D by cofilin: impact on the actin cytoskeleton
We have elucidated signaling pathways from the M3 muscarinic receptor that lead to the activation of
PLD. One pathway consists of the sequential activation of Rho-kinase and LIM-kinase by RhoA,
resulting in phosphorylation of the actin depolymerizing factor cofilin. Phosphorylated cofilin directly
interacts with and stimulates PLD1, disclosing a novel and exciting function of cofilin and a direct
connection between PLD and cytoskeleton organization (Han et al, EMBO J., 26, 4189-4202). Many
cellular tasks depend on dynamic actin reorganization, and PLD/cofilin interaction likely has a major
impact on cellular functioning. The role of PLD will be primarily analyzed in cells from the
cardiovascular system, but further promising possibilities and avenues are feasible, including the role
of PLD/cofilin in cytoskeletal rearrangements in vascular/airway smooth muscle remodeling, and
cellular adhesiveness.

Role of PLC potentiation in neuronal cells
It is almost axiomatic in neuroscience that postsynaptically induced long-term potentiation is a cellular
substrate of learning and memory formation. However, the signaling processes that support this form
of neuronal plasticity are incompletely understood. In contrast to most other signaling cascades that
are down-regulated upon continued receptor stimulation, we found that repeated triggering of
membrane receptors resulted in enhanced signaling by PLC. This interesting phenomenon likely
reflects a form of cellular memory, and we therefore started to characterize the molecular mechanism
of PLC potentiation. Recently, we demonstrated for the first time that Epac2 specifically modifies
memory retrieval (Ostroveanu et al, Hippocampus, in revision), and this research line delivered a
patent "Modulation of memory function"; P85114US00.

Regulation and cellular roles of phospholipase C-
We have successfully defined several signaling pathways from membrane receptors towards the
recently identified PLC- isoform (e.g. Schmidt et al, Nat. Cell Biol., 3, 1020-1024). Studies into the
involvement of PLC- in other cellular processes and specialized cell types are initiated, and
preliminary results indicate that PLC stimulation by the antigen receptor in B lymphocytes is
dependent on Epac proteins and Rap GTPases (Grandoch et al., Cell. Signal., 21, 609-621). As PLC-
is likely to represent a molecular switch between Ras and ERK1/2, which are reported to be implicated
in the bone morphogenetic protein (BMP) receptor pathway, our studies may further elucidate
signaling processes during stages of embryonic heart development (van Dijk et al., Circ. Res., in
revision).

Physiological role of Epac in chronic inflammatory disorders
The function of cells in the cardiovascular and neuronal system (cardiomyocytes, vascular smooth
muscle cells and neuronal cells) is strictly controlled by receptors that regulate the activity of ion
channels as well as the generation of the universal second messengers cAMP and Ca2+. cAMP
typically stimulates PKA, but recently, Epac proteins were identified as novel cAMP effectors, which
function as activators for Rap GTPases. As mentioned above, we have characterized a novel and
exciting signaling pathway from Gs-coupled receptors to PLC-, and these studies established Epac
proteins as essential cellular switches that connect changes in cAMP levels with cellular Ca 2+
homeostasis. With our powerful tools (combining in vitro and in vivo models), we collected recently
evidence that Epac driven signaling is of importance in physiological systems that likely depend on
cAMP/Ca2+ interactions or Rap GTPases, for instance integrin-mediated cell adhesion, cell migration
(tumorigenesis and cancer), embryonic heart development, neuronal diseases and chronic
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Dr. Martina Schmidt
inflammatory disorders. In particular, we gain insight into the spatio-temporal organization of cyclic
AMP signaling by identifying signaling complexes composed of AKAP-PKA-Epac (Nijholt et al.,
Cell. Signal., 20, 17150-1724), and focus on the impact of Epac signaling in B and T lymphocytes
(Grandoch et al., Cell. Signal., 21, 609-612; Grandoch et al., J. Leuk. Biol., in press). In addition, Epac
modulates hibernation and COPD (Nederlands Astma Fonds project). Of interest the impact of Epac
on hibernation, 'wintersleep', that makes animals cycle from low body temperature (full rewarming,
without organ damage). Evidently, this trick of nature may be exploited in 'harsh' conditions in man.
Limitations in time or metabolic-rate are beneficial in many medical conditions: severe trauma, organ
transplantation, cardiac arrest. Molecular mechanisms of hibernation are largely unexplored, but seem
to be related to Epac.