Laboratories

Molecular Biomedicine for Pathogenesis

Professor: Toru Miyazaki
Lecturer: Satoko Arai

1. Research
"New gene, New function, and New therapy"
Our laboratory will focus on clarification of the pathogenesis of various diseases and the related physiological machineries in cellular and molecular aspects. Based on our technical advantage in gene manipulation via gene knockout and transgenesis, we will give high priorities to in vivo analyses. This will definitively contribute to the direct therapeutic application of our findings.
Since our rationale is to challenge to uncharacterized disease mechanisms and physiologies, we will not restrict our interest, strategy or technique employed, in certain specific field. Rather, we will expand our research area by establishing different collaborations with a broad spectrum of investigators. We believe this fits to the policy of the CDBIM, which aims the development of a comprehensive science including the fundamental and clinical medicines, and the biotechnology. Overall, we will attempt to discover novel biological insights rather than to study details of previously characterized physiologies, by targeting molecules newly identified by ourselves. The major specific aims during the next five years are as follows:
  1. Role of AIM (Apoptosis Inhibitor of Macrophage) in the development of metabolic syndrome.
  2. Regulation of hematopoiesis and its relevance to leukemogenesis;
    via functional analysis of a newly identified Polycomb group molecule MBT-1.
  3. Regulation of tumorgenesis by modulating apoptosis and cell cycle;
    via analysis of DEDD-deficient animals.
2. Publications
  1. Kurokawa, J. et al. A dipose tissue macrophage-derived AIM is endocytosed into adipccytes and induces lipolysis via inhibition of fatty acid synthase activity. Cell Metab. (in press).
  2. Bhatia, H. et al. A short-chain fatty acid mediated reversed globin gene switch in primary definitive erythroid cells. Blood 113: 6440-8. (2009).
  3. Kurabe, N. et al. The death effector domain-containing DEDD supports S6K1 activity via preventing Cdk1-dependent inhibitory phosphorylation. J. Biol.Chem. 284: 5050-5055 (2009).
  4. Jayachandran, R. et al. Survival of Mycobacteria in macrophages is mediated by Coronin 1-dependent activation of calcineurin. Cell 130: 1-14 (2007).
  5. Miyazaki, T. & Arai, S. Two distinct controls of mitotic Cdk1/cyclin B1 requisite for cell growth prior to cell division. Cell Cycle 6: 1419 - 1425 (2007).
  6. Arai, S. et al. The death-effector domain containing protein DEDD is a novel mitotic inhibitor requisite for cell growth. Proc. Natl. Acad. Sci. USA 104: 2289-2294 (2007).
  7. Arai, S. et al. A role of the apoptosis inhibitory factor AIM/Spα/Api6 in atherosclerosis development. Cell Metabolism 1: 201-213 (2005).
  8. Arai, S. & Miyazaki, T. Impaired maturation of myeloid progenitor cells exhibiting normal proliferative activity in mice lacking the novel Polycomb group protein MBT-1. EMBO J. 24: 1863-1873 (2005).