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Systems Medicine

Overview

The sedentary lifestyle and rapid aging of the society are continuingly increasing the incidence and prevalence of non-communicable diseases (NCDs), such as cardiovascular and metabolic diseases. In particular, more and more patients now have combined dysfunctions in multiple organs (multimorbidity). In our lab, we aim to elucidate the molecular mechanism underlying the development of multimorbidity and translate the basic science into novel therapeutic and diagnostic strategies. Particular focuses are the crosstalk between multiple systems, such as immune, neural, cardiovascular and metabolic systems, and the molecular underpinning of the crosstalk.

Professor:
Ichiro Manabe, MD, PhD

TEL: +81-43-226-2964
FAX: +81-43-226-2964
e-mail: imanabe●chiba-u.jp
URL: http://plaza.umin.ac.jp/manabe/en/

※　Please change "●" mark to at-mark if you send emails.

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Research & Education

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  1. The hematopoietic stem cell - monocyte - macrophage continuum in multimorbidity
    We elucidate the alterations in the hematopoietic stem cells and their progenies as a unifying mechanism of multimorbidity.
  2. Homeostatic function of tissue macrophages and its alterations in NCDs
    Tissue macrophages, such as cardiac macrophages, are essential for maintaining homeostasis and proper stress response. We are analyzing the physiological functions of tissue macrophages and their modulations in NCDs. W also found that aging alters macrophage functions, which may promote tissue dysfunction and chronic inflammation in the elderly (inflammaging).
  3. Epigenetic and immunometabolic regulation of macrophages
    We are analyzing epigenetic regulatory mechanisms of macrophage function and differentiation. We are particularly interested in the mechanisms that generate diverse populations and/or activation states in macrophages.
  4. Organ crosstalk in homeostasis and NCDs
    We previously showed that inflammation in adipose tissue promotes inflammation in pancreatic islets, resulting in beta cell dysfunction (Cell Metab 2012). We also showed that the heart-brain-kidney network is essential for proper adaptive response to cardiac stress (Nat Med 2017). In these organ crosstalk, the metabolic, immune, endocrine, circulatory, and neural systems interact with each other. We are analyzing such inter-system interactions in physiology and diseases.
  5. Bioinformatics and computational analysis of big data
    We are developing software tools for analyzing various data generated by next-generation sequencing and modalities of single-cell analyses.

Recent Publications

  • Sugita J, Fujiu K, Manabe I, et al. Cardiac macrophages prevent sudden death during heart stress. Nat Commun 12:1910, 2021.
  • Liu L, Manabe I, Oishi Y, et al. Identification of a KLF5-dependent program and drug development for skeletal muscle atrophy. Proc Natl Acad Sci U S A 118:e2102895118, 2021.
  • Nakayama Y, Fujiu K, Manabe I, et al. A long noncoding RNA regulates inflammation resolution by mouse macrophages through fatty acid oxidation activation. Proc Natl Acad Sci USA 202005924, 2020.
  • Oishi Y, Manabe I. Organ System Crosstalk in Cardiometabolic Disease in the Age of Multimorbidity. Front Cardiovasc Med 7, 2020.
  • Abe H, Takeda N, Manabe I, et al. Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. Nat Commun 10:2824, 2019.
  • Oishi Y, Manabe I. Macrophages in inflammation, repair and regeneration. Int Immunol 30:511-528, 2018.
  • Fujiu K, Shibata M, Manabe I, et al. A heart-brain-kidney network controls adaptation to cardiac stress through tissue macrophage activation and cellular communication. Nat Med 23:611-622, 2017.
  • Hayashi S, Manabe I, et al. Klf5 regulates muscle differentiation by directly targeting muscle-specific genes in cooperation with MyoD in mice. eLife 2016;10.7554/eLife.17462.
  • Ogata F, Fujiu K, Manabe I, et al. Excess lymphangiogenesis co-operatively induced by macrophages and CD4+ T cells drives the pathogenesis of lymphedema. J Invest Dermatol 136:706-714, 2016.