Institute for Environmental and Gender-Specific Medicine
Iwao Sekigawa, MD, PhD.
PhD: Juntendo University School of Medicine (1987)
Education and Appointments:
1978 | Graduation from Fukushima Medical College (M.D.) |
1985-1988 | Juntendo University Faculty of Medicine, Department of Pathology, Instructor (Ph.D.) |
1988-1991 | Harvard Medical School, New England Deaconess Hospital Department Hematology/Oncology, Instructor |
1991-1995 | Juntendo University Faculty of Medicine, Department of Internal Medicine and Rheumatology, Instructor |
1995-2004 | Juntendo University Faculty of Medicine, Department of Internal Medicine and Rheumatology, Assistant professor |
2004-2008 | Juntendo University Faculty of Medicine, Department of Internal Medicine and Rheumatology, Associate professor Juntendo University Graduate School of Medicine, The Institute for Environment and Gender-Specific Medicine, Associate professor (concurrent) |
2008- | Juntendo University Faculty of Medicine, Department of Internal Medicine and Rheumatology, Professor
Juntendo University Graduate School of Medicine, The Institute for Environment and Gender-Specific Medicine, Professor (concurrent) |
Members:
Iwao Sekigawa MD,PhD: Sinji Morimoto MD,PhD: Keigo Ikeda MD,PhDKunihiro Hayakawa PhD: Tomoko Miyasita MD.PhD: Takuya Hirai MD
Hiroshi Tushima MD: Maki Fujisiro MS: Yuko Yoshida PhD: Minami Masuzawa
Mikiko Kawasaki PhD
Research Specialty:
The incidence of certain autoimmune diseases such as systemic lupus erythematosus (SLE) is well known to be far higher in females than in males. We are interested in the gender bias of autoimmune diseases, especially (SLE), and mainly investigating the mechanisms of such sexual differences.Research description:
1) The pathogenesis of SLE: We have been investigating the possible role of human endogenous retroviruses (HERV) on the induction of SLE, and reported the higher transcription and translation of HERV in SLE patients as compared to controls. We examine the mechanisms (especially epigenetic regulation, including DNA methylation and acethylation) of increased transcription of HERV in the patients with SLE.2) With reference to 1), we also investigate the fluctuation of gene expressions in SLE patients along with the disease activities using a DNA micro array method. The effect of sex hormones on gene expressions are also examined by using the same method. Furthermore, in order to make clear the mechanisms of gender bias of SLE, we are performing the quantitative and qualitative analyses of hormone (such as estrogen-alpha and beta) receptors in the patients with SLE.
3) Clinical studies relating to autoimmune diseases are also performed. For instance, we are investigating the relationship between fetal loss of mothers having with autoimmune diseases and certain autoantibodies, and the precise mechanisms of the therapeutic effect of anti-tumor necrosis factor (TNF)-alpha antibodies, which is a most recent treatment to rheumatoid arthritis (RA), on the patients with RA.In addition, through the case studies of patients with autoimmune and/or rheumatic diseases, we also explore the establishment of new clinical features or entities, as well as more effective therapeutic approaches for these disorders.
These studies seem to contribute to the elucidation of the pathogenesis of SLE or RA as well as the mechanisms of gender bias of these disorders, and the development of new treatments of them.
Research contents:
We are investigating the pathogenesis of autoimmune diseases including rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) using modern biological technologies such as mass spectrometry and DNA/RNA microarrays, and seeking new diagnostic/therapeutic approaches from data obtained in our research.1) Rheumatoid arthritis (RA): We are investigating the mechanisms underlying the efficacy of recently developed biological drugs for RA (including infliximab, etanercept, adalimumab and tocilizmab) using mass spectrometry. We have found that certain serum/plasma proteins show remarkable quantitative changes in RA patients before and after treatment. We are developing new therapeutic strategies and diagnostic technologies targeting these proteins, using RA model mice and human RA samples.
2) Systemic lupus erythematosus (SLE): We are investigating SLE-disease-activity-related genes in peripheral blood mononuclear cells (PBMC) from SLE patients using DNA microarray methods. Our data have suggested an important role of interferon regulatory genes (IFRg) in the activation of SLE. Furthermore, we found abnormal activities of IFRg-related gene cascades in SLE patients by using pathway network analysis. We have examined the therapeutic efficacy of a drug which has inhibitory effects on these gene cascades in model mice of SLE.3) Mechanisms of gender bias in incidence of autoimmune diseases such as SLE, RA, and Sjogren’s syndrome (SS) are also investigated in our laboratory. In addition, the role of microRNA in the translation/transcription of genes in RA and/or SLE are studied using the latest microRNA analysis technology.
Publications (2008-2015)
- Nakano S, Morimoto S, Suzuki S, Tsushima H, Yamanaka K, Sekigawa I, Takasaki Y.Immunoregulatory role of IL-35 in T cells of patients with rheumatoid arthritis. Rheumatology (Oxford). 54:1498-106,2015
- Nozawa K, Fujishiro M, Takasaki Y, Sekigawa I. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor. World J Orthopedics 18: 1-7, 2014.
- Suzuki S, Morimoto S, Fujishiro M, Kawasaki M, Hayakawa K, Miyashita T, Ikeda K, Miyazawa K, Yanagida M, Takamori K, Ogawa H, Sekigawa I, Takasaki Y. Inhibition of the insulin-like growth factor system is a potential therapy for rheumatoid arthritis. Autoimmunity. 2014 Oct 29:1-8. [Epub ahead of print]
- Yanagida M, Kawasaki M, Fujishiro M, Miura M, Ikeda K, Nozawa K, Kaneko H, Morimoto S, Takasaki Y, Ogawa H, Takamori K, Sekigawa I. Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with tocilizumab: an anti-interleukin-6 receptor antibody. Biomed Res Int 2013;2013:607137.Doi: 10.1155/2013/607137. Epub 2013 Aug 22101.
- Nozawa K, Fujishiro M, Kawasaki M, Yamaguchi A, Ikeda K, Morimoto S, Iwabuchi K, Yanagida M, Ichinose S, Morioka M, Ogawa H, Takamori K, Takasaki Y, Sekigawa I. Inhibition of connective tissue growth factor ameliorates rheumatoid arthritis in a murine model. Arthritis Rheum 65: 1477-1486, 2013
- Yanagida M, Jung G, Tanaka Y, Sone S, Fujishiro M, Ikeda K, Nozawa K, Kaneko H, Takasaki Y, Ogawa H, Takamori K, Sekigawa I. Serum proteome analysis in patients with rheumatoid arthritis receiving therapy with etanercept, a chimeric tumor necrosis factor-alpha receptor. Int J Rheum Dis 15: 486-495, 2012
- Yamaguchi A, Nozawa K, Fujishiro M, Kawasaki M, Suzuki F, Takamori K, Ogawa H, Takasaki Y, Sekigawa I. CC motif chemokine ligand 13 is associated with rheumatoid arthritis pathogenesis. Mod Rheumatol 23: 856-863, 2012
- Yamaguchi A, Nozawa K, Fujishiro M, Kawasaki M, Takamori K, Ogawa H, Sekigawa I, Takasaki Y. Estrogen inhibits apoptosis and promotes CC motif chemokine ligand 13 expression on synovial fibroblasts in rheumatoid arthritis. Immunopharmacol Immunotoxicol 34: 852-857, 2012
- Fujishiro M, Yamaguchi A, Kawasaki M, Nozawa K, Takasaki Y, Takamori K, Ogawa H, Endo K, Ng PS, Takehara K, Sekigawa I. The detection of plasma levels of connective tissue growth factor in rheumatoid arthritis patients. Clin Exp Rheumatol 30: 145-146, 2012
- Fujishiro M, Nozawa K, Kawasaki M, Yamaguchi A, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Fukui H, Kaneko K, Ogawa H, Takamori K, Takasaki Y, Sekigawa I. Regenerating gene (REG) 1 alpha promotes pannus progression in patients with rheumatoid arthritis. Mod Rheumatol 22: 228-237, 2012
- Kawasaki M, Fujishiro M, Yamaguchi A, Nozawa K, Kaneko H, Takasaki Y, Takamori K, Ogawa H, Sekigawa I: Possible role of the JAK/STAT pathways in the regulation of T cell-interferon related genes in systemic lupus erythematosus. Lupus 20: 1231-1239, 2011
- Kawasaki M, Fujishiro M, Yamaguchi A, Nozawa K, Kaneko H, Takasaki Y, Takamori K, Ogawa H, Sekigawa I: Fluctuations in the gene expression of peripheral blood mononuclear cells between the active and inactive phases of systemic lupus erythematosus. Clin Exp Rheumatol 28: 311-317, 2010.
- Sekigawa I, Fujishiro M, Yamaguchi A, Kawasaki M, Inui A, Nozawa K, Takasaki Y, Takamori K, Ogawa H: A new hypothesis of the possible mechanisms of gender differences in systemic lupus erythematosus. Clin Exp Rheumatol 28: 419-423, 2010.
- Nozawa K, Fujisiro M, Kawasaki M, Kaneko H, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Takasaki Y, Ogawa H, Takamori K, Sekigawa I: Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis: novel protective mechanism of articular destruction on anti-TNF-alpha blocking therapy. Arthritis Res Ther 11: R174, 2009.
- Kawasaki M, Sekigawa I, Nozawa K, Kaneko H, Takasaki Y, Takamori K, Ogawa H: Changes in the gene expression of peripheral blood mononuclear cells during the menstrual cycle of females is associated with a gender bias in the incidence of systemic lupus erythematosus. Clin Exp Rheumatol 27: 260-266, 2009.
- Sekigawa I, Yanagida M, Iwabuchi K, Kaneda K, Kaneko H, Takasaki Y, Jung G, Sone S, Tanaka Y, Ogawa H, Takamori K: Protein biomarker analysis by mass spectrometry in patients with rheumatoid arthritis receiving anti-tumor necrosis factor-α antibody therapy. Clin Exp Rheumatol 26: 261-267, 2008.