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Anja Nohe, Ph.D.
- Development of Delivery Techniques. Current research is limited in tools to transfect proteins into cells, especially the cell nucleus. We recently developed a new very efficient transfection technique for proteins and nanoparticles into the cell nucleus. Our method provides 70-80 percent transfection efficiency of primary cells and cell lines. The uptake is very rapidly, cells stay alive for at least 3 days. Studies show that the method is non invasive, making it a powerful transfection tool. We are currently working on the detailed mechanism of the delivery.
- Development of New Imaging Techniques. In order to study signal transduction in real time in live cells new imaging tools must be developed. One major goal of my research focuses on the further development of the Family of Image Correlation Spectroscopy (FICS), a powerful tool to measure protein dynamics, aggregation and signalling.
- Differentiation of Stem Cells: Role of Hormones and Growth factors. In general my laboratory is interested in determining molecular dynamics underlying stem cell differentiation. In detail I am interested in developing new imaging techniques and probes to study real time dynamics of signal transduction mechanisms. We are especially interested to develop new probes and delivery techniques and use these approaches to investigate the influence of nanoscale receptor dynamics underlying diseases such as cancer and osteoporosis.
- Toxicity of Nanoparticles. Since we are developing new tools and probes for imaging it is crucial to test the toxicity of our newly synthesized probes. Our preliminary results indicate that our synthesized quantum dots (QD's, small semiconductor nanoparticles) due to their size were acutely toxic to zebrafish embryos. Exposure of zebrafish to 30nM of QD's was lethal within 1 to 12h, depending upon the surface properties of the QD's. Moreover, confocal microscopy revealed that quantum dots accumulate within zebrafish embryos. An in vivo transgenic zebrafish model of metal induced transcription showed metal-mediated bioactivity after QD exposure. The magnitudes of bioaccumulation and bioactivity differed in our experiments depending upon the particular type of QD that was used for exposure. These results raise the question whether the surface properties of QD's can be correlated to particle uptake, cell death, and embryo survival. We are currently investigating how the size, charge, and composition of QD's affect the uptake, distribution, and toxicity of QD's in zebrafish embryos and cell lines.
Differentiation of Stem Cells
- Role of BMP in stem cell differentiation. We plan on identifying the role of our new identified proteins in BMP signaling and osteoblast differentiation. Moreover we want to test the effect of our developed peptides on Bone Marrow Stromal Cells isolated from mice exhibiting an age related osteoporotic phenotype. We expect that these peptides enhance osteoblast differentiation rather than fat cell differentiation. If this is the case these peptides could be potent new therapeutics for the treatment of osteoporosis.
- Role of IGF1 in stem cell differentiation. Insulin-like Growth Factor- I (IGF-I) is a critical peptide for skeletal growth and consolidation. The Bone group at The Jackson Laboratory identified a QTL for serum IGF-I, (Igflsl-1, LOD score ~9.0) located on Chromosome (Chr) 6. Dr. Rosen generated a congenic strain (B6.C3H-6T;6T), which resulted in a phenotype that included very low trabecular bone volume(BV/TV), reduced bone formation, impaired entry of stromal cells into the osteoblast lineage, acclerated marrow adiposity and insulin sensitivity. Female 6T congenics had ~20% lower serum IGF-I, as well as reduced skeletal and fat expression of this peptide. In preliminary studies, my laboratory found significant strain differences in the distribution of both caveolin 3 and the IGFR between 6T and B6. Hence, we want to analyze the effect of the clustering and aggregation of IGFR in caveolae on cell differentiation. We will do this by quantifying the co-localization of IGFR with caveolae in bone MSCs isolated from B6 and 6T mice and investigating the effect of co-localization of IGFR with caveolae on signal transduction and osteogenesis. Our preliminary results indicate that in these mice membrane aggregation is altered. These results suggest that membrane dynamics may play a crucial role for osteoblast differentiation and during osteoporosis. New therapeutics aimed to restore aggregation could be used as new therapeutics for the treatment of osteoporosis.
- Role of Vitamin D in Cancer. One of my current interests is to explore the molecular basis of cancer by establishing the role of 1,25 dihydroxy vitamin D3 (Vitamin D3) and its membrane receptor in hormone-dependent cancer cells, such as those of the breast, ovary, and prostate. In hormone-dependent cancers, tumor growth is driven by the binding of the hormone to its receptor. Vitamin D3 can have both preventive and therapeutic effects by regulating cell growth, the cell cycle, apoptosis, and differentiation Epidemiological studies have found a significant association between low serum levels and low dietary intake of Vitamin D3 and the incidence, degree of malignancy, metastases, and mortality of cancers of the breast, prostate, colon, and ovaries , . Based on this research, it has been proposed that taking 1,000 international units (IU) - or 25 micrograms - of Vitamin D3 daily could lower an individual's cancer risk by 50% in colon cancer, and by 30% in breast and ovarian cancer. The mechanism for Vitamin D3's chemoprevention not well-defined, but understanding how it works would provide vital information for targeting populations at high risk for developing hormone-dependent cancers. Additionally, it could lead to improved chemotherapies that are more individualized and less toxic.
- Shayamala Thinakaran, M.D. - Postdoctoral Fellow (M.D., Ross University). Understanding the role of interactions between BMP and EGF receptors in tumorigenesis of breast cancer.
- Jeremy Bonor, B.S. - (B.S., University of Maine).
- Beth Bragdon, B.S. - Graduate Student (B.S., University of Maine).
- Ingraham BA, Bragdon B, Nohe A. Molecular basis of the potential of vitamin D to prevent cancer. Curr Med Res Opin. 2008;24(1):139–149.
- Keating E, Nohe A, Petersen NO. Studies of distribution, location and dynamic properties of EGFR on the cell surface measured by image correlation spectroscopy. Eur Biophys J. 2008;37(4):469–481.
- Nohe A, Petersen NO. Image correlation spectroscopy. Sci STKE. 2007;2007(417):pl7.
- Nohe A, Keating E, Fivaz M, van der Goot FG, Petersen NO. Dynamics of GPI-anchored proteins on the surface of living cells. Nanomedicine. 2006;2(1):1–7.
- Nohe A, Keating E, Underhill TM, Knaus P, Petersen NO. Dynamics and interaction of caveolin-1 isoforms with BMP-receptors. J Cell Sci. 2005;118(Pt 3):643–650.
- Pohl F., Koelbl O., Flentje M., Nohe A. Analysis of the Formation of Heterotopic Ossifications in a Cell Model – Effects of Irradiation on Cellular Signalling Regarding the BMP-receptors. In: Leeds DT, ed. Focus on Cellular Signalling Research. Nova Science Publishers, Inc.; 2005:55–71.
- Kovar M., Nohe A., Petersen N.O., Norton P. Optical Imaging using NSOM. In: Photonics Handbook. Laurin publishing; 2004:H77–80.
- Nohe A, Petersen NO. Analyzing for co-localization of proteins at a cell membrane. Curr Pharm Biotechnol. 2004;5(2):213–220.
- Nohe A, Petersen NO. Analyzing protein-protein interactions in cell membranes. Bioessays. 2004;26(2):196–203.
- Nohe A, Keating E, Knaus P, Petersen NO. Signal transduction of bone morphogenetic protein receptors. Cell Signal. 2004;16(3):291–299.
- Nohe A, Keating E, Loh C, Underhill MT, Petersen NO. Caveolin-1 isoform reorganization studied by image correlation spectroscopy. Faraday Discuss. 2004;126:185–95; discussion 245–54.
- Hassel S, Schmitt S, Hartung A, et al. Initiation of Smad-dependent and Smad-independent signaling via distinct BMP-receptor complexes. J Bone Joint Surg Am. 2003;85-A Suppl 3:44–51.
- Nohe A, Keating E, Underhill TM, Knaus P, Petersen NO. Effect of the distribution and clustering of the type I A BMP receptor (ALK3) with the type II BMP receptor on the activation of signalling pathways. J Cell Sci. 2003;116(Pt 16):3277–3284.
- Pohl F, Hassel S, Nohe A, et al. Radiation-induced suppression of the Bmp2 signal transduction pathway in the pluripotent mesenchymal cell line C2C12: an in vitro model for prevention of heterotopic ossification by radiotherapy. Radiat Res. 2003;159(3):345–350.
- Nohe A., Petersen N.O. Image correlation spectroscopy: Exploring intramolecular interactions. Biophotonics. 2002;9:39–52.
- Nohe A, Hassel S, Ehrlich M, et al. The mode of bone morphogenetic protein (BMP) receptor oligomerization determines different BMP-2 signaling pathways. J Biol Chem. 2002;277(7):5330–5338.
- Gilboa L, Nohe A, Geissendorfer T, Sebald W, Henis YI, Knaus P. Bone morphogenetic protein receptor complexes on the surface of live cells: a new oligomerization mode for serine/threonine kinase receptors. Mol Biol Cell. 2000;11(3):1023–1035.
- Nohe A, Lermann G, Schwoerer H, Kiefer W, Sawatzki J, Surawicz G. High resolution low wavenumber Fourier transform Raman spectroscopy with a rubidium vapor filter and a Ti:sapphire laser. J Mol Struct. 1997;410:65–68.
- Nohe A., Lermann G., Schwoerer H., Kiefer W., Sawatzki J., Surawicz G. High Resolution/Low Wavenumber Fourier Transform Raman Spectroscopy with a Rubidium Vapor Filter and a Ti: Sapphire laser. In: Asher SA, Stein PB, eds. Proceedings of the XVth International Conference on Raman Spectroscopy. New York: Wiley; 1996:1240–1241.
Phone: (302) 831-2959
Fax: (302) 831-2281
Office: 324 Wolf Hall
Lab: 247 Wolf Hall
Department of Biological Sciences
University of Delaware
Newark, DE 19716
- Diplom. - University of Würzburg (Germany)
- Ph.D. - Theodor Boveri Institute, University of Würzburg (Germany)
- Postdoctoral - University of Western Ontario (Canada)