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- Tsutomu TAKEUCHI
Researcher's Profile
- Fellow
- Tsutomu TAKEUCHI
- RCAST Fellow
- tsutake
z5.keio.jp
Biography
| September 1984 | Keio University, Faculty of Medicine, PhD |
|---|---|
| January 1985 | Research Fellow, Tumor Immunology (Prof. Stuart F. Schlossman), Dana-Farber Cancer Institute, Harvard University |
| July 1998 | Professor of Internal Medicine, Division of Rheumatology, Department of Internal Medicine, Saitama Medical School |
| August 2004 | Vice President of Saitama Medial University |
| August 2009 | Professor of Internal Medicine, Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine |
| October 2013 | General Director of Keio University Hospital (October 1, 2013~July 31, 2017) |
| August 2017 | Vice President of Keio University |
| April 2021 | Emeritus Professor, Keio University |
| 2021 | Project Professor, Saitama Medical University |
| March 2022 | Fellow, RCAST, The University of Tokyo |
| April 2022 | Vice President of Saitama Medial University |
Research Interests
- Pathogenesis of systemic autoimmune diseases: My major research interests include the molecular understanding of systemic lupus erythematosus (SLE), rheumatoid arthritis, Sjogren’s syndrome, vasculitis, and other systemic autoimmune diseases. In particular, we aim to investigate the samples from the patients, coupled with the high-quality longitudinal clinical data from the patients. In 1990s, the peripheral blood from the patients with SLE were immunized to mice and generated a long list of monoclonal antibodies (mAbs) reacting with the patients’ peripheral lymphocytes. By screening with the increased expression of the molecules recognized by the mAbs in SLE patients, compared to healthy individual, we identified increased expression of alpha4beta1 (α4β1)integrin with vasculitis, increased alphaEbeta7(αEβ7) with epithelitis, and down-regulated TCR(CD3) zeta expression in SLE. More recently, we utilize, whole or cell-specific RNA expression with gene chip, single cell RNA sequencing, and CyTOF for the analysis on the peripheral blood, synovium, salivary glands, and kidney samples from the patients. For the analysis, I strongly try to obtain the combined data from the longitudinal sampling, depending on the appropriate timing on the treatment, and the high-quality standardized clinical data to provide high-quality and reproducible outp
- Prediction and monitoring biomarkers for systemic autoimmune diseases: Important clinical research topics is to search for the biomarkers of the predicting and activity-monitoring for the targeted treatment. We have been analyzed these biomarkers by whole blood, cell-subset specific transcriptome by gene-chip, serum, urine, and bronco-alveolar lavage fluids proteome by nucleic aptamer methods, and immune-phenotype, along with clinical, imaging, and pathological data. For example, longitudinal peripheral blood sampling from RA patients treated with methotrexate (MTX: anti-metabolite, first line therapy), anti-TNF mAbs, and anti-IL-6receptor mAbs with the above-described multi-omics molecular profiling were performed. Even though the comparable clinical remission was achieved at 6 months with MTX, anti-TNF, and anti-IL-6R, the molecular signatures were significantly different among the patients with different targeted treatment with clinical remission. We generated the algorithm for RA odds by multi-omics data and defined molecular remission with the RA odds. The patients with molecular remission at 6 months after targeted treatment is associated with more stable clinical course over two years, compared with clinical remission at 6 months, indicating that the molecular signatures such as molecular remission may be valuable for assessing the disease status at 6 months after targeted treatment. This is a first report for the significance of molecular remission in RA patients with targeted treatment.
- Clinical research for systemic autoimmune diseases: I participated in a number of pharmaceutical company-sponsored, physician initiated clinical trials and clinical studies as a principal investigator or an investigator. Particularly, I played a lead investigator for the global phase 3 clinical trials for RA with anti-IL-6 mAbs and Jak inhibitors. By these intense experiences with clinical trials and studies, I was nominated as a committee member for European League Against Rheumatism (EULAR) recommendation for RA in 2016 and 2019 and would be joining the meeting for 2022 revision as only one member from Japan.
- Framework for clinical trials and clinical study: From 2013 to 2017, I was nominated as general director of Keio University Hospital, one of the biggest university hospitals in Tokyo. During my term, the stable management of hospital and function as university hospital were refined and clinical trial center was established in Keio University Hospital in 2015, leading to the achievement of the certification of Core Hospital of Clinical Studies in Japan. By these experiences, I am continuously interested in evaluating and establishing the appropriate structure, strategy, human resources, and education for clinical study in academia and core hospitals.
Keywords
Autoimmune diseases, Molecular mechanism, Biological treatment, Clinical study
