Dr. Katharina

Wenzel-Seifert

Senior Scientist

Department of        Pharmaceutical Chemistry I

Chairman:

Prof. Dr. Sigurd Elz

    Curriculum vitae

• May 1986: Graduation from Medical School at the Free University of Berlin, Medical degree
• 1985-87: Postdoctoral fellow at the Institute of Clinical Physiology, Free University of Berlin
• 1987-90: Training in Internal Medicine at the Benjamin Franklin Klinikum, Free University of Berlin
• 1990-95: Postdoctoral fellow at the Institute of Pharmacology, Free University of Berlin
• 1995-98: Postdoctoral fellow at the Department of Molecular and Cellular Physiology, Howard Hughes Medical Institute, Stanford University (Brian Kobilka)
• 1998-2000: Research Associate at the Department of Pharmacology, University of Kansas
• 2000-2003: Research Assistant Professor at the Department of Pharmacology, University of Kansas
• since 2002: studies of history, political sciences and philosophy at the FernUniversität Hagen, Germany
• since October 2005: senior scientist

Fields of Research:

• 5-Hydroxytryptamine Receptors

5-hydroxytryptamine receptors (5-HTR) are G protein-coupling receptors (GPCRs). 5-HT_{2A, B, C} receptors couple with G proteins of the G_q family, whereas 5-HT₆R and 5-HT_7A and _B are G_s coupling receptors. In collaboration with Dr. Elz I will study the effects of several newly synthesized agonists and antagonists on these 5-HT receptor subtypes.

• Formyl Peptide Receptors

In the past ten years I worked mainly about human neutrophils which play a major part in the first-line host defense against invading microorganisms. My main topic were the classical leukocyte chemoattractants (N-formyl peptides, the activated complement fragment C5a, leukotriene B₄ (LTB 4 ), the phospholipid platelet-activating factor (PAF) and the cytokine interleukin-8 which bind to specific heptahelical G-protein-coupled receptors (GPCRs). The formyl peptide receptor is expressed in nearly every human tissue . However, its role besides host defense is still unclear. In several pathophysiological conditions such as ischemia-reperfusion injury (after stroke, myocardial infarction) and inflammatory or autoimmune diseases (e. g. juvenile periodontitis, renal diseases, Crohn's disease, ulcerative colitis, rheumatoid arthritis, multiple sclerosis, Behcet's disease) the inappropriate activation of phagocytes is often the major cause of tissue damage.
In my future studies I plan to characterize the signal transduction of so-called FPR-like receptors.

• β-Adrenoceptors

In a previous studies, our laboratory has shown that the β₂-adrenoceptor coupled to the long splice variant of G_sαL but not the β₂-adrenoceptor coupled to the short splice variant of G_sαS has the properties of a constitutively active receptor. These differences in receptor/G-protein coupling can be explained by differences in the GDP-affinity of G_sαS and G_sαL. Specifically, G_sαL has a lower GDP-affinity than G_sαS. Thus, the receptor activation energy required for releasing GDP from G_sαL is lower than the activation energy required for releasing GDP from G_sαS. As the result of this difference in activation energy, even the agonist-free β₂-adrenoceptor can efficiently promote GDP release from G s a L and partial agonists promote GDP-release at the G_sαL-coupled β₂-adrenoceptor more easily than at the G_sαS -coupled β₂-adrenoceptor. These properties of the G_sαL-coupled β₂-adrenoceptor constitute the hallmarks of constitutive activity.
One of the goals of research in our lab was to answer the question whether the differential coupling of a receptor to G_sα splice variants as a result of different GDP-affinities of the G-proteins is a mechanism that is of general pharmacological relevance. To address this question, fusion proteins of different G_s subunits coupling receptors and G_sα splice variants have been expressed in Sf9 cells. In the future, I will analyze the effects of a large series of receptor ligands on the GTPγS binding and adenylyl cyclase activity of β₁- and β₃-adrenoceptor G_sα fusion proteins.

Publication List