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Ali Naji, M.D., Ph.D.
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Jonathan E. Rhoads Professor of Surgical Science II
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Attending Staff, Hospital of the University of Pennsylvania
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Associate Director, Institute for Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine
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Department: Surgery
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Graduate Group Affiliations
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- Immunology e
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Contact information
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University of Pennsylvania Medical Center
1c 2 Founders Courtyard
3a 3400 Spruce Street
Philadelphia, PA 19104-4283
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1c 2 Founders Courtyard
3a 3400 Spruce Street
Philadelphia, PA 19104-4283
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Office: (215) 662-2066
34 Fax: (215) 615-4900
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34 Fax: (215) 615-4900
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Email:
ali.naji@uphs.upenn.edu
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ali.naji@uphs.upenn.edu
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Education:
21 c Diploma c
54 Shiraz University School of Arts and Sciences, Shiraz, Iran, 1964.
21 c Diploma c
4c Shiraz University School of Medicine, Shiraz, Iran , 1968.
21 9 None c
58 University of Pennsylvania School of Medicine, Philadelphia, PA, 1969.
21 9 M.D. c
38 Shiraz University, Shiraz, Iran, 1970.
21 a Ph.D. 17 (Immunology) c
58 University of Pennsylvania School of Medicine, Philadelphia, PA, 1981.
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Permanent link21 c Diploma c
54 Shiraz University School of Arts and Sciences, Shiraz, Iran, 1964.
21 c Diploma c
4c Shiraz University School of Medicine, Shiraz, Iran , 1968.
21 9 None c
58 University of Pennsylvania School of Medicine, Philadelphia, PA, 1969.
21 9 M.D. c
38 Shiraz University, Shiraz, Iran, 1970.
21 a Ph.D. 17 (Immunology) c
58 University of Pennsylvania School of Medicine, Philadelphia, PA, 1981.
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92 Mechanisms regulating the maintenance and loss of immune tolerance to tissue specific antigens in autoimmune diseases and transplantation
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18 Research Summary
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466 Autoimmune diabetes serves as an important paradigm for the loss of immune tolerance to tissue specific autoantigen(s) mediated by the activation of islet-reactive T lymphocytes. The non-obese diabetic (NOD) mouse is an excellent model for study of the immune pathogenesis of human insulin-dependent diabetes mellitus. NOD mice spontaneously develop overt diabetes as a result of the selective, T cell mediated destruction of insulin producing b cells of the islets of Langerhans. Elucidation of the cellular nature of the antigen presentation driving the evolution of a destructive anti-islet T cell response is one main focus of the laboratory. Based on our finding that B cell deficient NOD mice are fully resistant to the development of autoimmune diabetes, we have hypothesized that the progression of the islet-specific T cell response in NOD mice is dependent on antigen presentation by B lymphocytes. Specifically, ongoing research is focused on determining the role of: 1) MHC class II mediated cognate T/B collaboration and 2) BCR and non-BCR mediated means of antigen uptake by APCs in NOD diabetogenesis.
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539 Another major effort in the laboratory is the elucidation of the mechanisms contributing to the maintenance of T cell tolerance and the parameters favoring its dysregulation. The fate and activation requirements of T cells specific for tissue restricted neo- and allo- antigens will be studied in the context of spontaneous autoimmune disease and following transplantation of cellular and solid organ allografts. Specifically, an MHC class II restricted, CD4+ TCR transgenic model is utilized to study the phenotype, homing patterns, and pathogenic potential of autoreactive T cells, 1) developing in the milieu of tissue restricted neo-antigen expression and 2) encountering neo- antigens present in transplanted organs. Furthermore, using bone marrow chimeras we have investigated the mechanisms of immunologic tolerance mediated by T cell deletion and anergy to alloantigens. Ongoing studies are focused on defining the antigen presenting requirements determining the shape of the alloreactive T cell repertoire and its functional state. Understanding the basic parameters dictating the state of tolerance and activation requirements of T cells reactive to tissue restricted autoantigens, as well as alloantigens, will permit the design of therapeutic means aimed at modulating the response of auto- and allo-reactive T cells.
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Description of Research Expertise
23 Research Interest8
92 Mechanisms regulating the maintenance and loss of immune tolerance to tissue specific antigens in autoimmune diseases and transplantation
8
18 Research Summary
8
466 Autoimmune diabetes serves as an important paradigm for the loss of immune tolerance to tissue specific autoantigen(s) mediated by the activation of islet-reactive T lymphocytes. The non-obese diabetic (NOD) mouse is an excellent model for study of the immune pathogenesis of human insulin-dependent diabetes mellitus. NOD mice spontaneously develop overt diabetes as a result of the selective, T cell mediated destruction of insulin producing b cells of the islets of Langerhans. Elucidation of the cellular nature of the antigen presentation driving the evolution of a destructive anti-islet T cell response is one main focus of the laboratory. Based on our finding that B cell deficient NOD mice are fully resistant to the development of autoimmune diabetes, we have hypothesized that the progression of the islet-specific T cell response in NOD mice is dependent on antigen presentation by B lymphocytes. Specifically, ongoing research is focused on determining the role of: 1) MHC class II mediated cognate T/B collaboration and 2) BCR and non-BCR mediated means of antigen uptake by APCs in NOD diabetogenesis.
8
539 Another major effort in the laboratory is the elucidation of the mechanisms contributing to the maintenance of T cell tolerance and the parameters favoring its dysregulation. The fate and activation requirements of T cells specific for tissue restricted neo- and allo- antigens will be studied in the context of spontaneous autoimmune disease and following transplantation of cellular and solid organ allografts. Specifically, an MHC class II restricted, CD4+ TCR transgenic model is utilized to study the phenotype, homing patterns, and pathogenic potential of autoreactive T cells, 1) developing in the milieu of tissue restricted neo-antigen expression and 2) encountering neo- antigens present in transplanted organs. Furthermore, using bone marrow chimeras we have investigated the mechanisms of immunologic tolerance mediated by T cell deletion and anergy to alloantigens. Ongoing studies are focused on defining the antigen presenting requirements determining the shape of the alloreactive T cell repertoire and its functional state. Understanding the basic parameters dictating the state of tolerance and activation requirements of T cells reactive to tissue restricted autoantigens, as well as alloantigens, will permit the design of therapeutic means aimed at modulating the response of auto- and allo-reactive T cells.
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e5 Alfrey EJ, Campos L, Naji A, Barker CF, and Dafoe DC: Liver Allografts Confer Donor Specific Tolerance to Transplanted Islets in Rats. 2001 Notes: In Press.
114 Greeley SAW, Moore DJ, Noorchashm H, Noto L, Rostami SY, Schlachterman, A, Song HK, Koeberlein B, Barker CF, and Naji A: Impaired Lymph Node CD4 T-Cell Activation in MT-/-NOD Mice. 2001 Notes: Submitted.
1a1 Wu, H., Wasik, MA., Haynes, B., Moore, H.C.F., Leonard, D.G.B., Montone, K.T., Kamoun, M., Przybylski, G., Naji, A., Tomaszewski, J., and Salhany, K.: Hepatosplenic γδ T-Cell Lymphoma as a Late-Onset Posttransplant Lymphoproliferative Disorder in Renal Transplant Patients. American Journal of Clinical Pathology. 113(4): 487-496, April 2000.
18b Shaw, L.M., Korecka, M., Aradhye, S., Grossman, R., Bayer, L., Innes, C., Cucciara, A., Barker, C., Naji, A., Nicholls, A. and Brayman, K.: Mycophenolic Acid Area Under the Curve Values in African American and Caucasian Renal Transplant Patients are Comparable. Journal of Clinical Pharmacology. 40(6): 624-633, June 2000.
188 Noorchashm, H., Moore, D.J., Noto, L.E., Noorchashm, N, Reed, A.J., Reed, A.L., Song, H.K., Mozaffari, R., Jevnikar, A.M., Barker, C.F., and Naji, A.: Impaired CD4 T Cell Activation Due to Reliance upon B-Cell Mediated Costimulation in Non-Obese Diabetic (NOD) Mice. Journal of Immunology. 165: 4685-4696, October 2000.
15d Larson, R.A., Naji, M., Lombardi, J.V., Naji, A., Koeberlein, B., Golden, M.A. Ryan, S.: Adenoviral-Mediated Uteroglobin Gene Transfer Inhibits Neointimal Hyperplasia after Balloon Injury in the Rat Carotid Artery. Journal of Vascular Surgery. 32(6): 1111-1117, December 2000.
167 Noorchashm, H., Moore, D.J., Lieu, Y.K., Noorchashm, N., Schlacterman, A., Song, H.K., Lambris, J.D., Barker, C.F., and Naji, A.: Contribution of the Innate Immune System to Autoimmune Diabetes: A Role for the Cr1/Cr2 Complement Receptors. Cellular Immunology. 195(1): 75-79, July 1999.
1b1 Noorchashm H., Lieu Y.K., Noorchashm N, Rostami S.Y., Greeley, S.A.S., Schlacterman A., Song H.K., Noto, L.E., Jevnikar A.M., Barker C.F., and Naji A.: I-A g7-Mediated Antigen Presentation by B Lymphocytes Is Critical in Overcoming a Checkpoint in T Cell Tolerance to Islet β Cells of Nonobese Diabetic Mice. Journal of Immunology. 163(2): 743-750, July 1999.
103 Song, H.K., Noorchashm, H., Lieu, Y.K., Rostami, S., Greeley, S.A.S., Barker, C.F., and Naji, A.: Tracking Alloreactive Cell Division In Vivo. Transplantation. 68(2): 297-299, July 1999.
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Selected Publications
13c Jordan, M.S., Boesteanu, A., Reed, A.J., Petrone, A.L., Holenbeck, A., Lerman, M.A., Naji, A., and Caton, A.J.: Thymic Selection of CD4+ CD25+ Regulatory T Cells Induced by an Agonist Self-Peptide. Nature Immunology. 2(4): 301-306, April 2001.e5 Alfrey EJ, Campos L, Naji A, Barker CF, and Dafoe DC: Liver Allografts Confer Donor Specific Tolerance to Transplanted Islets in Rats. 2001 Notes: In Press.
114 Greeley SAW, Moore DJ, Noorchashm H, Noto L, Rostami SY, Schlachterman, A, Song HK, Koeberlein B, Barker CF, and Naji A: Impaired Lymph Node CD4 T-Cell Activation in MT-/-NOD Mice. 2001 Notes: Submitted.
1a1 Wu, H., Wasik, MA., Haynes, B., Moore, H.C.F., Leonard, D.G.B., Montone, K.T., Kamoun, M., Przybylski, G., Naji, A., Tomaszewski, J., and Salhany, K.: Hepatosplenic γδ T-Cell Lymphoma as a Late-Onset Posttransplant Lymphoproliferative Disorder in Renal Transplant Patients. American Journal of Clinical Pathology. 113(4): 487-496, April 2000.
18b Shaw, L.M., Korecka, M., Aradhye, S., Grossman, R., Bayer, L., Innes, C., Cucciara, A., Barker, C., Naji, A., Nicholls, A. and Brayman, K.: Mycophenolic Acid Area Under the Curve Values in African American and Caucasian Renal Transplant Patients are Comparable. Journal of Clinical Pharmacology. 40(6): 624-633, June 2000.
188 Noorchashm, H., Moore, D.J., Noto, L.E., Noorchashm, N, Reed, A.J., Reed, A.L., Song, H.K., Mozaffari, R., Jevnikar, A.M., Barker, C.F., and Naji, A.: Impaired CD4 T Cell Activation Due to Reliance upon B-Cell Mediated Costimulation in Non-Obese Diabetic (NOD) Mice. Journal of Immunology. 165: 4685-4696, October 2000.
15d Larson, R.A., Naji, M., Lombardi, J.V., Naji, A., Koeberlein, B., Golden, M.A. Ryan, S.: Adenoviral-Mediated Uteroglobin Gene Transfer Inhibits Neointimal Hyperplasia after Balloon Injury in the Rat Carotid Artery. Journal of Vascular Surgery. 32(6): 1111-1117, December 2000.
167 Noorchashm, H., Moore, D.J., Lieu, Y.K., Noorchashm, N., Schlacterman, A., Song, H.K., Lambris, J.D., Barker, C.F., and Naji, A.: Contribution of the Innate Immune System to Autoimmune Diabetes: A Role for the Cr1/Cr2 Complement Receptors. Cellular Immunology. 195(1): 75-79, July 1999.
1b1 Noorchashm H., Lieu Y.K., Noorchashm N, Rostami S.Y., Greeley, S.A.S., Schlacterman A., Song H.K., Noto, L.E., Jevnikar A.M., Barker C.F., and Naji A.: I-A g7-Mediated Antigen Presentation by B Lymphocytes Is Critical in Overcoming a Checkpoint in T Cell Tolerance to Islet β Cells of Nonobese Diabetic Mice. Journal of Immunology. 163(2): 743-750, July 1999.
103 Song, H.K., Noorchashm, H., Lieu, Y.K., Rostami, S., Greeley, S.A.S., Barker, C.F., and Naji, A.: Tracking Alloreactive Cell Division In Vivo. Transplantation. 68(2): 297-299, July 1999.
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