Links:
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Research Program
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Faculty Laboratories:
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| Andrew Mellor, PhD |
| David Munn, MD |
| Pandelakis Koni, PhD |
| Michiko Shimoda, PhD |
| Affiliated Faculty: |
| Yukia He, MD, PhD |
Pandelakis A. Koni, PhD
email: pkoni@mcg.edu
Office: 706-721-6897
Lab: 706-721-7710
Research Emphasis:
My laboratory investigates the mechanisms whereby the immune system is regulated and how this knowledge might be translated into new therapeutics for the treatment of autoimmune diseases, cancer and infectious disease. One ongoing project is concerned with the interface between antigen-presenting cells and T cells with a specific interest in major histocompatibilty complex class II (MHC-II)-dependent events mediated by various, still incompletely defined, subsets of antigen-presenting cells, including B cells and dendritic cells (DCs). This involves the use of Cre/loxP conditional knockout mouse technology as well as various other whole animal and in vitro tools. A second project is concerned with soluble mediators of communication between cells of the immune system, specifically the interleukin-(IL-)12 family member IL-27 and other novel family members. Another such family member, IL-23, is implicated in inflammatory bowel diseases, diseases that are certainly of interest to our laboratory. Another project is concerned with the roles of DC in the gut in maintaining tolerance to food allergens and how they are influenced in the gut by dietary fiber products both in health and in mouse models of inflammatory bowel diseases. Last but not least, our laboratory has expertise in B cells not only as antigen-presenting cells but as the source of antibodies. B cells make antibodies in response to immune priming, and T cell-dependent long-term antibody protection is the basis for many vaccines. We are currently working on a novel mouse model of T cell-independent antibody generation, which we believe provides new opportunities for generating antibodies as tools, and in particular to generate antibodies to complex non-protein structures such as carbohydrates on pathogenic organisms.
As the Director of the Mouse ES Cell & Transgenesis Core Facility, I also oversee four staff members who provide various services, including generation of transgenic and knockout mice, to investigators in the University of Georgia system on a fee-for-service basis. Knockout mice are generated on a pure C57BL/6 background using our own C57BL/6 embryonic stem cells (external publication link). Our C57BL/6 knockout mouse efforts have also been greatly facilitated by our in-house trials with (C3HxBALB/c)F1 blastocysts for the generation of ES cell chimeras (external publication link).
Research Tools:
TIE2Cre transgenic mouse line 12: this line is backcrossed to a C57BL/6J background and is available from JAX mice as B6.Cg-Tg(Tek-Cre)12Flv/J. This line causes deletion of loxP-flanked targets in hematopoietic and endothelial progenitor cells, and was originally described in a publication in which we studied mice engineered with loxP sites for conditional deletion of vascular cell adhesion molecule-1 (external publication link).
TIE2Cre transgenic mouse line 27: this is a sister line of the above line 12. I have not yet published a description of this line but it was employed by our collaborators to cause endothelial cell-restricted deletion of a loxP-flanked STAT3 (external publication link), which unlike line 12 above also causes deletion in hematopoietic progenitor cells.
CD8a-Cre knock-in mouse: contains the Cre recombinase open reading frame knocked into the de novo CD8a gene such that the Cre recombinase start codon is in place of the CD8a start codon (not yet published). The Cre recombinase sequence is followed by an internal ribosomal entry sequence that drives expression of CD8a, but reconstitution of CD8a expression is only about 13% of the wild type level. Also, the degree of deletion of loxP-flanked targets in populations of CD8 T cells and CD8a-expressing dendritic cells is only about 70%. Efficiency in CD8a intraepithelial lymphocytes is being determined.
Cell-permeable Cre recombinase: we have generated a modified Cre recombinase that mediates deletion of loxP-flanked targets in primary cells as well as cell lines in vitro by simply adding this Cre recombinase protein to cell cultures (external publication link).
Laboratory members:
Mayuko Iwasaki and Sushama Wakade.
Mouse ES Cell & Transgenesis Core Facility Members:
Suzanne M. Dederscheck, Silvia Leanhart, Gabriela Pacholczyk, Rupali Suhag.
Selected recent publications:
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Pacholczyk G., Suhag R., Mazurek M., Dederscheck S.M. and Koni P.A. (2008). Generation of C57BL/6 knockout mice using C3HxBALB/c blastocysts. BioTechniques 44:413-416.
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Ou R., Zhang M., Huang L., Koni. P.A.* and Moskophidis, D.* (2008). Regulation of immune response and inflammatory reactions against viral infections by VCAM-1. J. Virol. 82:2952-2965. (*co-corresponding authors) (abstract)
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Shimoda M. and Koni P.A. (2007). MHC-II-restricted B cell antigen presentation in memory B cell maintenance and differentiation. Crit. Rev. Immunol. 27:47-60. (abstract)
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Shimoda M., Mmanywa F., Joshi S.K., Li T., Miyake K., Pihkala J.P.S., Abbas J.A. and Koni P.A. (2006). Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. J. Immunol. 176:6503-6511. (abstract)
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Shimoda M., Li T., Pihkala J.P.S. and Koni P.A. (2006). Role of MHC-II on memory B cells in post-germinal center B cell homeostasis and memory response. J. Immunol. 176:2122-2133. (abstract)
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Cavanagh L.L., Bonasio R., Mazo I.B., Halin C., Cheng G., van der Velden A.W.M., Cariappa A., Chase C., Russell P., Starnbach M.N., Koni P.A., Pillai S., Weninger W. and von Andrian U.H. (2005). Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells. Nature Immunol. 6:1029-1037. (abstract)
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Joshi S.K., Hashimoto K. and Koni P.A. (2002). Induced DNA recombination by Cre recombinase protein transduction. Genesis 33:48-54. (abstract)
- Koni P.A., Joshi S.K., Temann U.-A., Olson D., Burkly L. and Flavell R.A. (2001). Conditional vascular cell adhesion molecule 1 deletion in mice: impaired lymphocyte migration to bone marrow. J. Exp. Med. 193:741-753. (abstract)