Immunology Graduate Group
Nina Luning Prak, M.D., Ph.D.
Assistant Professor, Pathology and Laboratory Medicine
Address: 405B Stellar Chance Labs,
422 Curie Blvd., Philadelphia PA 19104
Office Phone: (215) 746-5768
Lab Phone: (215) 746-5769
Fax: (215) 573-6317
Email: luning@mail.med.upenn.edu
Education:
M.D., University of Pennsylvania
Ph.D., University of Pennsylvania
A.B., Princeton University
Research Interests
- Regulation of mobile DNA in somatic cells.
- Antibody gene rearrangement in normal and autoimmune B cells.
- L1 retrotransposon mouse models .
Research Summary
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Chromosomal DNA is not static in somatic cells- it can transpose or rearrange. We are interested in how DNA mobility is regulated in mammalian cells. The two types of mobile DNA that we study are antibody genes and L1 retrotransposons.
Antibodies are important components of our immune system, protecting us from extracellular pathogens and toxins. Antibodies can also recognize self molecules. Such autoantibodies can cause autoimmune diseases such as systemic lupus erythematosus (SLE). We are interested in how antibody production is controlled in normal and in autoimmune-prone B cells. Antibodies are assembled from gene segments by DNA rearrangement. B cells that "break the rules" of normal gene rearrangement may promote autoimmune disease. One form of rule breaking is the expression of more than one kind of antibody per B cell (allelic inclusion). We believe that allelically included B cells may serve as precursors to autoimmune B cells. To study antibody gene rearrangement, we use mice with genetically simplified immunoglobulin genes. Currently the lab is using an anti-DNA antibody heavy chain knock-in mouse called 56R. This heavy chain, when paired with almost every light chain, produces anti-DNA antibodies. By tracking the light chain usage, we can monitor the fate of autoreactive and allelically included B cells in vivo.
L1 retrotransposons (LINE1 elements, L1s) are mobile DNA elements that replicate via an RNA intermediate. The human genome contains over 500,000 L1 insertions of which only approximately 80 can move. Highly active L1s could be harnessed for a variety of biomedical applications including gene delivery, insertional mutagenesis and cell lineage analysis. We, along with Haig Kazazian, have constructed a transgenic mouse model of L1 retrotransposition using an active human L1 element tagged with green fluorescent protein (GFP). Our long-term aim is to use L1 transgenic mice to study where, when and how often L1 elements move and how L1 mobility is regulated in vivo. Several mechanisms have been postulated to limit L1 mobility including methylation and RNA interference (RNAi). In addition to RNA and RNAi studies, we are pursuing whether states such as transformation, neoplasia, injury (by DNA damaging agents) or even normal aging could result in greater L1 activity.
Recent Publications
Li, H., Jiang, Y., Cao, H., Radic, M., Luning Prak, E., and M. Weigert. 2003. "Regulation of anti-phosphatidylserine antibodies," Immunity 18: 185-192.
Luning Prak, E., Dodson, A.W., Farkash, E. A. and H. H. Kazazian. 2003. "Tracking an embryonic L1 retrotransposition event," Proc. Natl. Acad. Sci. (U.S.A.) Vol. 100 No. 4: 1832-1837.
Louzoun, Y., Friedman, T., Luning Prak, E., Litwin, S. and M. Weigert. 2002. "Analysis of B cell receptor production and rearrangement. Part 1. Light chain rearrangement." Semin. Immunol. 14 (3): 169.
Li, H., Jiang, Y., Luning Prak E., Radic, M. and M. Weigert. 2001. "Editors and Editing of anti-DNA receptors," Immunity Vol. 15: 947-957.
Luning Prak, E. and H. H. Kazazian. 2000. "Mobile elements and the human genome." Nature Genetics Reviews Vol. 1: 134-144.
Ostertag, E., Luning Prak, E., DeBerardinis, R., Moran, J.V. and H. H. Kazazian. 2000. "Determination of L1 retrotransposition kinetics in cultured cells." Nucl. Acids Res. Vol. 28(6): 1418-1423.
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