Member, Cancer Immunology, Inflammation and Tolerance Program
GRU Cancer Center
Associate Professor of Medicine
Basic Science Faculty
1120 15th Street, CN 4154
Phone: (706) 721-6897
The Koni 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 and cancer. One 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. This involves the use of Cre/loxP conditional knockout mouse technology and various other whole animal and in vitro tools. Another project is concerned with antigen-presenting cells in the gut in maintaining tolerance to innocuous food allergens and how they are influenced in the gut by dietary fiber products both in health and in mouse models of inflammatory bowel disease.
Last but not least, the Koni laboratory has expertise in B cells, not only as antigen-presenting cells, but also as a 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. The Koni laboratory is developing and investigating a novel mouse model of T cell-independent antibody generation, which is anticipated to provide new opportunities for the generation of antibodies as tools and therapeutics, and in particular to generate antibodies against non-protein structures such as carbohydrates on pathogenic organisms and tumor cells.
Mouse ES Cell and Transgenesis Core Facility
Dr. Koni also oversees four staff members who provide services, including transgenic and knockout mouse generation, to investigators in the University of Georgia System on a fee-for-service basis. C57BL/6 knockout mouse generation has also been greatly facilitated by in-house trials of novel blastocysts, with subsequent implementation of the use of (C3HxBALB/c)F1 blastocysts, for the generation of ES cell chimeras .
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. The line was originally described in a publication in which mice engineered with loxP sites for conditional deletion of vascular cell adhesion molecule-1 were described.
TIE2Cre transgenic mouse line 27
This is a sister line of the above line 12. A thorough description of this line has not yet been published, but it was employed by our collaborators to cause endothelial cell-restricted deletion of a loxP-flanked STAT3, which is unlike line 12 above that also causes deletion in hematopoietic progenitor cells.
CD8a-Cre knock-in mouse.
This 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 percent 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 percent. Efficiency in CD8a intraepithelial lymphocytes is being determined.
Cell-permeable Cre recombinase.
This is 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.
Getting rid of cancer means, at least in part, out-maneuvering the immune system. Instead of recognizing cancer cells as a threat, the immune system typically suppresses the body’s defenders, the lymphocytes, T cells and others. Dr. Koni and other investigators are looking for ways, such as vaccines, to alert the immune system.
“There are trials going on, but they are not entirely successful because there is a lot we still need to learn about the basic biology of the immune cells,” he says.
In 1990, Dr. Koni earned a BSc at the University of Warwick, UK, and three years later a PhD at the University of Cambridge, UK. Between January, 1994, and March, 1995, he did postdoctoral training at the Babraham Institute, UK, followed by four years at the Yale University School of Medicine, New Haven, Conn., with Dr. R.A. Flavell. Dr. Koni has contributed to nearly 40 articles in peer-reviewed professional journals.
- Bill and Melinda Gates Foundation: Antibody-Dependent Cellular Cytotoxicity Targeted Against HIV-1 Env Glycans: Grand Challenges Explorations Grant. 2010, Koni, PA, PI
Grant information is updated quarterly.
ad hoc reviewer:
- American Journal of Pathology
- Journal of Immunology
Sharma MD, Hou DY, Baban B, Koni PA, He Y, Chandler PR, Blazar BR, Mellor AL, Munn DH. Reprogrammed foxp3(+) regulatory T cells provide essential help to support cross-presentation and CD8(+) T cell priming in naive mice. Immunity. 2010 Dec 14;33(6):942-54.
Bolduc A, Long E, Stapler D, Cascalho M, Tsubata T, Koni PA, Shimoda M.Constitutive CD40L expression on B cells prematurely terminates germinal center response and leads to augmented plasma cell production in T cell areas. J Immunol. 2010 Jul 1;185(1):220-30.
Johnson BA 3rd, Kahler DJ, Baban B, Chandler PR, Kang B, Shimoda M, Koni PA, Pihkala J, Vilagos B, Busslinger M, Munn DH, Mellor AL. B-lymphoid cells with attributes of dendritic cells regulate T cells via indoleamine 2,3-dioxygenase. Proc Natl Acad Sci U S A. 2010 Jun 8;107(23):10644-8.
Igyarto BZ, Jenison MC, Dudda JC, Roers A, Müller W, Koni PA, Campbell DJ, Shlomchik MJ, Kaplan DH. Langerhans cells suppress contact hypersensitivity responses via cognate CD4 interaction and langerhans cell-derived IL-10. J Immunol. 2009 Oct 15;183(8):5085-93.
Baban B, Chandler PR, Sharma MD, Pihkala J, Koni PA, Munn DH, Mellor AL. IDO activates regulatory T cells and blocks their conversion into Th17-like T cells. J Immunol. 2009 Aug 15;183(4):2475-83.
Takabatake Y, Sugiyama T, Kohara H, Matsusaka T, Kurihara H, Koni PA, Nagasawa Y, Hamano T, Matsui I, Kawada N, Imai E, Nagasawa T, Rakugi H, Isaka Y. The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature. J Am Soc Nephrol. 2009 Aug;20(8):1714-23.
Sharma MD, Hou DY, Liu Y, Koni PA, Metz R, Chandler P, Mellor AL, He Y, Munn DH. Indoleamine 2,3-dioxygenase controls conversion of Foxp3+ Tregs to TH17-like cells in tumor-draining lymph nodes. Blood. 2009 Jun 11;113(24):6102-11.
Liston A, Nutsch KM, Farr AG, Lund JM, Rasmussen JP, Koni PA, Rudensky AY. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11903-8.
Pacholczyk G, Suhag R, Mazurek M, Dederscheck SM, Koni PA. Generation of C57BL/6 knock-out mice using C3HxBALB/c blastocysts. BioTechniques 2008;44:413-6.
Ou R, Zhang M, Huang L, Koni PA, Moskophidis D. Regulation of immune response and inflammatory reactions against viral infections by VCAM-1. J. Virol. 2008;82:2952-65.
Publications are updated quarterly. For a complete listing, see Dr. Koni’s work on PubMed
Liston A, Nutsch KM, Farr AG, Lund JM, Rasmussen JP, Koni PA, Rudensky AY. Differentiation of regulatory Foxp3+ T cells in the thymic cortex. PNAS USA. 2008;105:11903-8.
Pacholczyk G, Suhag R, Mazurek M, Dederscheck SM, Koni PA. Generation of C57BL/6 knockout mice using C3HxBALB/c blastocysts. BioTechniques. 2008;44:413-6.
Ou R, Zhang M, Huang L, Flavell RA, Koni PA*, Moskophidis D.* Regulation of immune response and inflammatory reactions against viral infections by VCAM-1. J. Virol. 2008;82:2952-65. (*co-corresponding authors)
Shimoda M, Koni PA. MHC-II-restricted B cell antigen presentation in memory B cell maintenance and differentiation. Crit. Rev. Immunol. 2007;27:6047-59.
Shimoda M, Mmanywa F, Joshi SK, Li T, Miyake K, Pihkala JPS, Abbas JA, Koni PA. Conditional ablation of MHC-II suggests an indirect role for MHC-II in regulatory CD4 T cell maintenance. J. Immunol. 2006;176:6503-11.
Shimoda M, Li T, Pihkala JPS, Koni PA. Role of MHC- class II on memory B cells in post-germinal center B cell homeostasis and memory response. J. Immunol. 2006;176:2122-33.
Cavanagh LL, Bonasio R, Mazo IB, Halin C, Cheng G, van der Velden AWM, Cariappa A, Chase C, Russell P, Starnbach MN, Koni PA, Pillai S, Weninger W and von Andrian UH. Activation of bone marrow-resident memory T cells by circulating, antigen-bearing dendritic cells. Nature Immunol. 2005;6:1029-37.
- Associate Professor, Medical College of Georgia and College of Graduate Studies, Georgia Health Sciences University
- Member, American Association for the Advancement of Science
- Member, American Association of Immunologists
- Member, British Society for Immunology
- Member, International Cytokine Society