Angela Rösen-Wolff - Characterization of the molecular mechanisms that influence phagocyte functions

Previous and current research

Phagocytes are large white cells that engulf and digest marauding microorganisms and other antigenic particles. Important phagocytes are monocytes and macrophages. Monocytes circulate in the blood, then migrate into tissues whereby they develop to macrophages. Macrophages are seeded throughout the body tissues in a variety of guises. Specialised macrophages include alveolar macrophages in the lungs, mesangial phagocytes in the kidneys, microglial cells in the brain, Kupffer cells in the liver, and osteoclasts in bone. Impairment of monocyte functions leads to a variety of human diseases, some of which have been studied by my group: Chronic granulomatos disease (CGD), a defect of NADPH oxidase in neutrophils and monocytes, which leads to a severe immunodeficiency, Tumor necrosis factor alpha receptor associated periodic syndrome (TRAPS) which is associated with periodic fever, and Interferon-gamma receptor deficiencies leading to severe infections with atypical mycobacteria.

Future prospects and goals

Future projects
Future projects will deal with the identification of cellular mechanisms which are involved in pathogenesis of the diseases mentioned above: The role of monocytes in granuloma formation in CGD will be characterized in an in vitro model and the formation of endosomes in interferon-gamma receptor deficient cells will be studied. In addition the cell biological characterization of remodelling of bone by osteoclasts is another main future project. In this connection the influence of bone matrix proteins on these cells is of special interest.

Goals
The goal of our studies is to understand the various functions of phagocytes in different tissues on a molecular level in order to develop novel approaches to therapy of diseases which are caused by impairment of phagocyte functions.

Selected publications

Khattak, S., Darai, G., Süle, S. and Rösen-Wolff, A. (2002): Characterization of expression of Puumala virus nucleocapsid protein in transgenic plants. Intervirology, 45: 334-339

Khattak, S., Darai, G. and Rösen-Wolff, A. (2004): Puumala virus nucleocapsid protein expressed in transgenic plants is not immunogenic after oral administration. Virus Genes, 29: 109-116

Rösen-Wolff, A., Koch, A., Friedrich, W., Hahn, G., Gahr, M. and Roesler, J. (2004): Successful elimination of an invasive Aspergillus nidulans lung infection by voriconazole after failure of a combination of caspofungin and liposomal amphotericin B in a boy with chronic granulomatous disease. Ped Inf Dis., J 23: 584-586

Pörksen, G., Rösen-Wolff, A., Heyden, S., Förster, T., Wendisch, J., Heubner, G., V. Bernuth H, Sallmann S, Gahr M, Roesler J (2004): Periodic fever, mild arthralgias, and reversible moderate and severe organ inflammation associated with V198M mutation in the CIAS1 gene in three German patients – expanding phenotype of CIAS1 related autoinflammatory syndrome CRAS. Eur J Hematol., 72: 1-5

Rösen-Wolff, A., Quietsch, J., Schröder, H., Lehmann, R., Gahr, M. and Roesler, J. (2003): Two German CINCA (NOMID) patients with different clinical severity and response to anti-inflammatory treatment. Eur J Hematol., 71: 215-219)

Angela Rösen-Wolff

1986: MD, University of Heidelberg, Germany

1991: PhD, University of Heidelberg, Germany

1986-1991: Resident at the Institute of Medical Virology, University of Heidelberg, Germany

1991-1993: Resident at the Hygiene Institute, University of Heidelberg, Germany

since 1995: Head of the Dept. of Clinical Research at the Dept. Of Pediatrics, Medical Faculty, Dresden University of Technology