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I hold a Ph.D. (2001) in Biological Sciences from the University of Erlangen-Nuernberg, Germany. I joined the Scrable Lab in March 2002, where I am a Research Associate. My interest is in investigating the HI-Virus, the agent that causes Acquired Immunodeficiency Syndrome (AIDS). My research focuses on an accessory protein of HIV, called Nef. Nef is a 27 kDa protein which is expressed early in the viral life cycle. In vitro functions of Nef (see Figure 1) are interference with cell signaling pathways (Fig. 1, Nr. 1), CD4 (Fig. 1, Nr. 2) and MHCI downregulation and enhancement of viral infectivity (Fig. 1, Nr. 3). In vivo Nef is an important pathogenesis factor during the progression of the disease.
The goal of my research is to develop an animal (mouse) model to explore the function of Nef at the organismal level. The lac repressor regulatory system developed and successfully used in our lab will allow me to study the function of the Nef protein by regulating it's expression temporally and spatially. To express Nef tissue specifically in CD4+ T-cells, which are the target cells of HIV, Nef will be expressed under the control of the CD4 promoter, which is active only in CD4+ T-cells. To make the CD4 promoter temporally regulatable, lac operator sequences will be introduced into the promoter region. At specific times Nef than can be activated with the lactose analogue IPTG. Presently, I am inserting lac operator sequences at different positions into the CD4 promoter and I am testing the activity and the regulatability of the modified CD4 promoter in cell culture.
Being stable and reversible, this mouse model will be an excellent in vivo system to investigate Nef function and the pathogenic mechanisms by which HIV-1 destroys the mammalian immune system.
Figure 1: The three in vitro functions of Nef. 1. Interference with cell signaling pathways.
2. CD4 downregulation. 3. Enhancement of viral infectivity
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Publications:·
- Wolf D., Witte V., Laffert B., Blume K., Stromer E., Trapp S., D'Aloja P., Schürmann A. and Baur A. S. (2001)HIV-1 Nef associated PAK and PI3-Kinases stimulate Akt-independent Bad-phosphorylation to induce anti-apoptotic signals. Nature Medicine 7, 1217-1224
- Fackler O. T./Wolf D., Weber H. O., Laffert B., D'Aloja P., Schuler-Turner B., Geffin R., Saksela K., Geyer M., Peterlin B. M., Schuler G. and Baur A. S. (2001)A natural variability in the proline-rich motif of Nef modulates HIV-1 replication in primary T cells. Curr. Biol. 11, 1294-1299
- Geffin R./Wolf D., Müller R., Hill M. D., Stellwag E., Freitag M., Sass G., Scott G. B. and Baur A. S. (2000). Functional and Structural Defects in HIV-1 nef Genes Derived from Pediatric Long-term Survivors. AIDS Res. Hum. Retroviruses 16, 1855-1868
- Xu X.-N./Laffert B., Screaton G. R., Kraft M. S., Wolf D., Kolanus W., Mongkolsapay J., McMichael A. J. and Baur A. (1999). Induction of Fas ligand expression by HIV involves the interaction of Nef with the T cell receptor zeta chain. J.Exp.Med. 189, 1489-1496
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