Principal Investigator & Distinguished Senior Research Scientist
Edison Biotechnology Institute

J.O. Watson Endowed Chair for Diabetes Research
Department of Biomedical Sciences
College of Osteopathic Medicine

Education

1957
B.A.
Columbia College, New York, NY

1961
M.D.
Columbia College of Physicians and Surgeons, New York, NY

Research associates

Scientific Staff
Eric Dickerson, Molecular Biology Technician
Kelly McCall, Post-doctoral Fellow

Research interests

My group and I focus on how autoimmune disease begins — the mechanism of onset, particularly of endocrine autoimmunity (Graves' disease, diabetes). Our goal is to discover new drugs for treatment of these conditions.

We also study regulation of the growth and function of the thyroid and the basis for self-tolerance. Then we evaluate the mechanism of transcriptional regulation of MHC gene expression and its link to hormonal regulation and self-tolerance.

Our projects in collaboration with academic and business partners include:

Drug development for treating autoimmune disease. A potential "lead" agent useful in treating autoimmune problems in systemic lupus and Type 1 diabetes has been identified based on in vitro and in vivo studies.

Drug development for treating inflammatory disease associated with increases in adhesion molecule gene expression and leukocyte adhesion. The agent in the above-mentioned program has been shown to selectively inhibit VCAM-1> E-selectin but not affect ICAM-1 in human arterial endothelial cells (HAEC). It inhibits leukocyte binding to HAEC and does this in a novel manner: inhibition of IRF-1 gene expression. The drug has been tested in a disease model, DSS-induced colitis, and shown to be efficacious. The agent thus has both anti-inflammatory and anti-immune properties. A related model evaluating its in vivo action in atherosclerosis and vascular complications of diabetes, which has a pathogenic basis similar to colitis, will be evaluated.

Drug development for treating innate immunity. The agent in the aforementioned programs has been found to be effective in blocking innate immune responses involved in disease development, such as toxic shock. Its usefulness in vivo has been established in mice.

Diagnostics. Improved methods to measure thyrotropin receptor autoantibodies, using transfected cells with chimeric receptors, have been developed. They are being beta tested in clinical settings and for production assays.

Clinical data base and tissue repository. A clinical data base and repository for endocrine disease, with a primary focus on diabetes and its complications, has been established. The results are of potential interest to drug companies and other commercial partners.

Professional activities and memberships

American Society of Biological Chemists, member from 1970
American Thyroid Association, member from 1978
American Endocrine Society, member from 1986
Honorary Member, Japan Endocrine Society, 1994
Honorary Doctorate of Medicine, University of Chieti, Italy, 1999
Ingbar Award: American Thyroid Association 1999
Member, Editorial Board, Endocrinology, 1995-1999, 2000 to present
Member, Editorial Board, Thyroid, 1990 to 2000

Interthyr Research Foundation:
A Non-Profit Supporting Endocrine Research
Board of Directors, 1982 to present
Treasurer, 1988 to present

Interthyr Corporation
President and CSO, 2000 to present

Selected publications

Kohn, L. D., Schwartz, F., Silver, M. J., and Goetz, D. J.: Toll-like Receptors in Nonimmune Cells and Environmental Induction of the Pathologic Expression of Innate Immunity and Autoimmune Inflammatory Diseases: A New Therapeutic Opportunity. Ohio Research and Clinical Review, 15, Spring, in press (2005).

Sakhalkar, H. S., Hanes, J., Fu, J., Benavides, U., Borruso, C. L., Kohn, L. D., Kurjiaka, D. T., and Goetz, D. J.: Enhanced Adhesion of Ligand-Conjugated Biodegradable Particles to Colitic Venules. FASEB Journal, 19, March (2005).

Harii, N., Lewis, C. J., Vasko, V., McCall, K., Benavides-Peralta, U., Sun, X., Ringel, M. D., Saji, M., Giuliani, C., Napolitano, G., Goetz, D. J., and Kohn, L. D.: Thyrocytes Express a Functional Toll-like Receptor 3 (TLR3): Overexpression Can Be Induced by Viral Infection, Reversed by Phenylmethimazole, and Is Associated with Hashimoto's Autoimmune Thyroiditis. Mol. Endocrinol., 19, 1231-1250 (2005).

Yoshida, A., Hisatome, I., Taniguchi, S., Sasaki, N., Yamamoto, Y., Miake, J., Fukui, H., Shimizu, H., Okamura, T., Okura, T., Igawa, O. Shigemasa, C., Green, E. D., Kohn, L. D., Suzuki, K.: Mechanism of iodide/chloride exchange by pendrin. Endocrinology, 145, 4301-4308 (2004).

Grassadonia, A., Tinari, N., Fiorentino, B., De Tursi, M., Suzuki, K., Nakazato, M., A., Giuliani, C., Napolitano, G., Singer, D. S., Iacobelli, S., and Kohn, L. D.: The 90K protein increases MHC class I expression and is regulated by hormones, gamma-interferon, and double-strand polynucleotides. Endocrinology, 145, 4728-4736 (2004).

Fuse, M., Tanaka, T., Shibata, T., Yoshida, T., Noguchi, Y., Misawa, N., Yasuda, T., Saito, Y., Kohn, L. D., Tatsuno, I.:Regulation of geranylgeranyl pyrophosphate synthase in the proliferation of rat FRTL-5 cells: involvement of both cAMP-PKA and PI3-AKT pathways. Biochem. Biophys. Res. Commun., 315, 1147-1153 (2004).

Dagia, N. M., Harii, N., Meli, A. E., Sun, X., Lewis C. J., Kohn, L. D., and Goetz, D. J.: Phenylmethimazole inhibits TNF-alpha-induced VCAM-1 expression in and IRF-1-dependent manner and reduces monocyte cell adhesion to endothelial cells. J. Immunology, 173, 2041-2049 (2004).

Wang, P., Sun, S-H., Silver, P. B., Chan, C-C., Wiggert, B., Agarawal, R. K., Jamieson, G. A., Kohn, L. D., and Caspi, R. R.: Methimazole protects from experimental autoimmune uveitis (EAU) by inhibiting antigen presenting cell function and reducing antigen priming. J. Leukocyte Biol., 73, 57-64 (2003).

Saunier, B., Triyatni, M., Ulianich, L., Maruvada, P., Yen, P., and Kohn, L. D.: The role of asialoglycoprotein receptor in the binding and entry of hepatitis C structural proteins in cultured human hepatocytes. J. Virology, 77, 546-559 (2003).

Pacifico, F., Montuori, N., Mellone, S., Liguoro, D., Ulianich, L., Caleo, A., Troncone , G., Kohn, L. D., Di Jeso, B., and Consiglio, E.: The RHL-1 subunit of the asialoglycoprotein receptor of thyroid cells: cellular localization and its role in thyroglobulin endocytosis. Mol. Cell. Endocrinol., 208: 51-59 (2003).

Molteni, M., Rossetti, C., Scrofani, S., Bonara, P., Scorza, R., and Kohn, L. D.: Regulatory CD8+ T cells control thyrotropin receptor-specific CD4+ clones in healthy subjects. Cancer. Detect. Prev. 27, 167-174 (2003).

Kohn, L. D. and Shong, M.: Thyrotropin receptor signaling. Encyclopedia of Medicine, in press (2003).

Kohn, L. D. And Harii, N.: Thyrotropin receptor autoantibodies (TSHYRAbs): Epitopes, Origins, and Clinical significance. Autoimmunity. 36, 331-338 (2003).

Kim, H., Suh, J. M., Hwang, E. S., Kim, D.W., Chung, H. K., Song, J. H., Hwang, J. H., Park, K. C., Kwon, O-Y., Ro, H. K., Cho, E-K., Lee, M. S. Kohn, L. D., and Shong, M.: TSH-mediated repression of class II transactivator (CIITA) expression in thyroid cells: involvement of signal transducer of transcription 3(STAT3) and suppreessor of cytokine signaling (SOCS). J. Immunol. 171, 616-27 (2003).

Kim, T. Y., Park, Y. J., Park, D. J., Chung, H.-K., Kim,W. B., Kohn, L. D. and Cho, B. Y.: Prediction of Outcome in Patients with Graves’ Disease after Antithyroid Drug Treatment According to Epitope Heterogeneity of Thyroid-Stimulating Antibodies. J. Clin. Endocrinol. Metab. 88, 117-124 (2003).

Yoshida, A., Taniguchi, S., Hisatome, I., Royaux, I. E., Green, E. D., Kohn, L. D., and Suzuki, K.: Pendrin is an iodide-specific apical porter responsible for iodide efflux from the cell. J. Clin. Endocrinol. Metab. 87, 3356-3361 (2002).

Suzuki, K., Royaux, I. E., Everett, L. A., Mori-Aoki, A., Suzuki, S., Nakamura, K., Sakai, T., Katoh, R., Toda, S., Green, E. D., and Kohn, L. D.: Expression of PDS/Pds, the Pendred Syndrome Gene, in Endometrium. J. Clin. Endocrinol. Metab., 87, 938-941 (2002).

Rotman-Pikielny, P., Hirschberg, K., Maruvada, P., Suzuki, K., Royaux, I. E., Green, E. D., Kohn, L. D., Lippencott-Schwartz, J., Yen, P.M.: Retention of Pendrin in the endoplasmic reticulum is a major mechanism for Pendred Syndrome. Human Molecular Genetics, 11, 2625-2633 (2002).

Napolitano, G., Bucci, I., Giuliani, G., Massafra, C., Di Petta, C., Devangelio, E., Singer, D. S., Monaco, F., Kohn, L. D.: High glucose levels increase MHC class I gene expression in thyroid cells and amplify interferon-gamma action. Endocrinology, 143, 1008-1017 (2002).

Suzuki, K., Yanagi, M., Mori-Aoki, A., Moriyama, E., Ishii, K. J., and Kohn, L. D.: Replication of Hepatitis Type A virus RNA directly induces MHC class I in cultured hepatocytes. Clinical and Experimental Immunology, 127:234-242, (2001).

Nakazato, M. Chung, H-K., Ulianich, L., Suzuki, K., and Kohn, L. D.: Thyroglobulin repression of thyroid transcription factor (TTF)-1 gene expression is mediated by decreased DNA binding of nuclear factor 1 proteins which control constitutive TTF-1 expression. Mol. Cell. Biol. 20, 8499-8512 (2000).

Kohn, L. D., Napolitano, G., Singer, D. S., Moltini, M., Scorza, R., Shimojo, N., Kohno, Y., Mozes, E., Nakazato, M., Ulianich, L., Chung, H-K., Matoba, H., Saunier, B., Suzuki, K., Schuppert, F., and Saji, M.: Graves’ disease: a host defense mechanism gone awry. Int. Rev. Immunol., 19, 633-644 (2000).

Suzuki, K., Mori, A., Ishii, K. J., Saito, J., Singer, D. S., Klinman, D. M., Krause, P. R., and Kohn, L. D.: Activation of target tissue immune recognition molecules by double strand polynucleotides. Proc. Natl. Acad. Sci. U. S. A., 96, 2285-2290 (1999).

Suzuki, K., Lavaroni, S., Mori, A., Ohta, M., Saito, J., Pietrarelli, M., Singer, D. S., Kimura, S., Katoh, R., Kawaoi, A., and Kohn, L. D.: Autoregulation of thyroid-specific gene transcription by thyroglobulin. Proc. Natl. Acad. Sci., U. S. A., 95, 8251-8256 (1998).

Montani, V., Shong, M., Taniguchi, S.-I., Suzuki, K., Giuliani, C., Napolitano, G., Saji, M., Fiorentino, B., Reimold, A. M., Singer, D. S., and Kohn, L. D.: Regulation of major histocompatibility (MHC) class II gene expression in thyrocytes: opposite effects of interferon and methimazole. Endocrinology, 139, 290-302 (1998).

Singer, D. S., Mozes, E., Kirshner, S., and Kohn, L. D.: Role of MHC class I molecules in autoimmune disease. Critical Reviews in Immunology, 17, 463-468 (1997).

Saji, M., Shong, M, Napolitano, G., Palmer, L. A., Taniguchi, S-I., Ohmori, M., Ohta, M., Suzuki, K., Kirshner, S. L., Giuliani, C., Singer, D. S., and Kohn, L. D.: Regulation of major histocompatibility class I gene expression in thyroid cells: role of the cAMP response element-like sequence. J. Biol. Chem., 272, 20096-20107 (1997).

Shimojo, N., Kohno, Y., Yamaguchi, K-I., Kikuoka, S-I., Hoshioka, A., Niimi, H., Hirai, A., Tamura, Y., Saito, Y., Kohn, L. D., and Tahara, K.: Induction of Graves’-like disease in mice by immunization with fibroblasts transfected with the thyrotropin receptor and a class II molecule. Proc. Natl. Acad. Sci. U, S. A., 93, 11074-11079 (1996).

Ohmori, M., Shimura, H., Shimura, Y., and Kohn, L. D.: A Y-Box protein is a suppressor factor which decreases thyrotropin receptor (TSHR) gene expression. Mol. Endocrinol., 10, 76-89 (1996).

Shimura, H., Shimura, Y., Ohmori, M., Ikuyama, S., and Kohn, L. D.: Single strand DNA-binding proteins and thyroid transcription factor-1 conjointly regulate thyrotropin gene expression. Mol Endocrinol., 9, 527-539 (1995).

Kohn, L. D., Shimura, H., Shimura, Y., Hidaka, A., Giuliani, C., Napolitano, G., Ohmori, M., Laglia, G., and Saji, M.: The Thyrotropin Receptor. In Litwack, G (Ed): Vitamins and Hormones, 50, 287-384 (1995).

Giuliani, C., Saji, M., Napolitano, G., Palmer, L. A. Taniguchi, S-I., Shong, M., Singer, D. S., and Kohn L. D.: Hormonal modulation of Major Histocompatibility Complex Class I Gene expression involves an Enhancer A binding complex consisting of Fra-2 and the p50 subunit of NF-cappa-B. J. Biol. Chem.,270, 11453-11462 (1995).

Kohn, L. D., Giuliani, C., Montani, V., Napolitano, G., Ohmori, M., Ohta, M., Saji, M., Schuppert, F., Shong, M-H., Suzuki, K., Taniguchi, S-I., Yano, K., and Singer, D. S.: Antireceptor Immunity. In Rayner, D. and Champion B. (Eds): Thyroid Immunity. R. G. Landes Biomedical Publishers, Austin/Georgetown, Texas, 115-170 (1995).