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My laboratory is focussed on understanding the mechanisms of pulmonary immunity and pulmonary fibrosis and on studying the regulation and development of anti-leukemic activity in syngeneic graft versus-host disease.
Experiments from our laboratory were the first to show that BLM-induced pulmonary fibrosis could be induced in SCID mice in the absence of lymphocytes and that fibrosis under those conditions were associated with profound eosinophilia. More recent studies have shown that BLM-induced fibirosis occurred in anti-IL-5 knockout mice in the absence of eosinophilia as well as in NK deficient mice suggesting that neither cell type was required for the induction of fibrosis. Currently, the levels and kinetics of fibrogenic and anti-inflammatory cytokines are being elucidated to determine their role in fibrosis. In addition, we have adopted a transgenic mouse strategy to deplete monocytes and consequently inflammatory macrophages by expressing an inducible suicide gene for the macrophage specific promoter, cfms, to express green fluorescent protein (GFP) and a suicide gene containing two units of FK506 binding protein (FKBP) fused to the cytoplasmic region of Fas. Dimerization of the FKBP with the drug AP20187 activates fas-mediated apoptosis and results in a dramatic reduction in GFP+ macrophages. In addition, these Tg mice develop an interesting clinical syndrome that includes massive adhesions and inflammation, the mechanism of which is currently under study.
We are also studying the mechanisms responsible for the induction of murine cyclosporine A-induced syngeneic graft-versus-host disease (SGVHD). Ongoing work in this model has ranged from describing the regulation and pathogenesis associated with the induction and adoptive transfer of this disease, to analysis of T cell clones isolated from diseased animals. It has been shown clinically that a beneficial consequence of GVHD following bone marrow transplantation (BMT) is the generation of anti-tumor or graft-versus-leukemia (GVL) responses and similarly mice with SGVHD have demonstrated the ability to reject syngeneic tumors. We are currently studying three aspects of SGVHD: 1) the immunoregulatory events that are responsible for induction of the disease; 2) the mechanism of GVL activity with particular focus on innate immunity; and 3) the induction and regulation of a Crohn’s/colitis like autoimmune disease which appears to be a prominent feature of SGVHD.
Perez J., Brandon J.A., Cohen D.A., Jennings C.D., Kaplan A.M., Bryson J.S.Accumulation of CD4+ T cells in the colon of CsA-treated mice following myeloablative conditioning and bone marrow transplantation. Am J Physiol. Gastrointest Liver Physiol. [Epub, 2011, Feb. 3]. PDF
Brandon, J.A., C.D. Jennings, A.M. Kaplan and J.S. Bryson. Murine syngeneic graft-versus-host disease is responsive to broad-spectrum antibiotic therapy. J. Immunol. 2011. 186:3726-34. [Epub 2011 Feb 4] PDF
Zhan Ye, A. M. Uittenbogaard, D.A. Cohen, A. M. Kaplan, J. Ambati and S.C. Straley. Distinct CCR2+ Gr1+ Cells Control Growth of YopM- Yersinia pestis in Liver and Spleen During Systemic Plague. Infect Immun. 79:674-87, 2010. [Epub 2010 Dec 13] PDF
Ahmed, A.L., E.K. Zuba-Suma, K.M. Ziada, KM. Kucia, D. A. Cohen. A.M. Kaplan, G.Van-Zant, S.Selim, S. S. Smyth, and M. Z. Ratajczak. Evidence of mobilization of pluripotent stem cells into peripheral blood of patients with myocardial ischemia. Exp Hematol. 38:1131-1142. Epub 2010 Aug 26. PDF
Brandon, J.A., C.D. Jennings, A.M. Kaplan and J.S. Bryson. Development of a TH17 immune response during the induction of murine syngeneic graft-versus- host disease. Cytokine. 52:265-273, 2010. Epub 2010 Sep 15.
Brandon, J.A., J. Perez, C.D. Jennings, A.M. Kaplan and Bryson, J.S. Association between chronic liver and colon inflammation during the development of murine syngeneic graft-versus-host disease. Am. J. Physiol. Gastrointest. Liver Physiol. 299:G602-G613, 2010. Epub 2010 Jul 15. PDF
Zeng L, O’Connor, CO, Zhang,J, Kaplan AM and DA Cohen. IL-10 Promotes Resistance to Apoptosis and Metastatic Potential in Lung Tumor Cell Lines. In Cytokine. 49:294-302, 2010.
Zhan Y, Kerschen, EJ, , Cohen, DA, Kaplan, AM, van Rooijen, N and Straley, SC. Gr1+ Cells Control Growth of YopM-Negative Yersinia pestis during Systemic Plague. Infection and Immunity. 77:3791-3806, 2009. PDF
Qualls, J.E., Tuna, H., Kaplan, A.M., and Cohen, D.A. Supression of Experimental Colitis in Mice by CD11c+ Dendritic Cells. Inflammatory Bowel Disease. 15:236-247, 2009. PDF
Jose, P., Avdiushko, R., Akira, S., Kaplan, A.M., and Cohen, D.A. Modulation of IL-10 signaling in lung dendritic cells by TLR-4 ligand lipopolysaccharide. Experimental Lung Research. 35:1-28, 2009. PDF
Bryson, JS, Jennings CD, Brandon, JA, Perez, J, Caywood, BE, and Kaplan, AM. Adoptive transfer of murine syngeneic graft-versus-host disease by CD4+ T cells. J. Leukocyte Biol. 82:1393-1400, 2007. PDF
Brandon J., Jennings, C.D., Perez, J., Caywood, B., Alapat, D., Kaplan, A.M., and Bryson, J.S. Induction of murine syngeneic graft-versus-host-disease by cells of recipient origin. Transplantation. 83:1620-1627, 2007. PDF
Qualls J., Kaplan A.M. and Cohen D.A. Protective role of intestinal macrophages during experimental colitis. J. Leukocyte Biol. 80:802-815, 2006. PDF
Schwertfeger, Kathryn L., Xian, Wa, Kaplan, Alan M., Burnett, Sandra H.Burnett. A critical role for the inflammatory response in a mouse model of preneoplastc progression. Cancer Res 66:5676-5685, 2006. PDF
Burnett, S.H., Beus, B.J., Avdiushko, R, Qualls, J., Kaplan, A.M. and Cohen, D.A. Development of peritoneal adhesions in macrophage depleted mice. J. Surgical Research. 131:296-301, 2006. PDF
Philipovskiy A.V., Cowan C., Wulff-Strobel C.R., Burnett S.H., Kerschen E.J., Cohen, D.A., Kaplan, A.M. and Straley, S.C. Antibody against V antigen prevents Yop-dependent growth of Yersinia pestis. Infection and Immunity 73:1532-1542, 2005. PDF
Hongo, D., Bryson, S., Kaplan, A.M., Cohen, D.A. Endogenous nitric oxide protects against T cell-dependent lethality during graft-vs-host disease and idiopathic pneumonia syndrome. J. Immunology. 173:1744-1756, 2004. PDF
Kerschen, E.J., Cohen, D.A., Kaplan, A.M., Straley, S.C. The plague virulence protein Yop M targets the innate immune response by causing global depletion of NK cells. In revision. Infect. Immunity. 72:4589-4602, 2004. PDF
Burnett, S., Kershchen, E.J., Zhang, J., Zheng, L., Straley, S., Kaplan, A.M., and Cohen, D.A. Conditional macrophage ablation in transgenic mice expressing a Fas-based suicide gene. J. Leukocyte Biol. 75:612-623, 2004. PDF
Bryson, J.S., Zhang, L., Goes, S.W., Jennings, C.D., Caywood, B.E., Carlson, S.L. and Kaplan, A.M. CD4+ T cells mediate murine syngeneic graft-versus-host disease-associated colitis. J. Immunology. 172:679-687, 2004. PDF
Fernandez, S., Jose, P., Avdiushko, M., Kaplan, A.M. and Cohen, D.A. Inhibition of IL-10 receptor function in the lung by Toll-Like receptor agonists. J. Immunology. 172:2613-2620, 2004. PDF