Research

Laboratory of Molecular Cell Biology

Professor Takanori So, Ph.D.
Associate Professor Masashi Morita, Ph.D.
Assistant Professor Kosuke Kawaguchi, Ph.D.

Our laboratory investigates how cellular proteins regulate signal transduction, metabolic reactions, and organelle functions and seeks to understand how dysfunction of these cellular events leads to the development of diseases in the immune and nervous system.

Novel cytokine receptor signaling mechanisms in immune cells that are regulated by TRAF and TNF-related molecules

The mammalian tumor necrosis factor (TNF) receptor-associated factor (TRAF) is composed of six family molecules that contain characteristic C-terminal TRAF domains. It has been demonstrated recently that intracellular TRAFs which associate with many different receptors expressed by immune cells including T-lymphocytes control signal transduction via these receptors in both positive and negative ways and in a context-dependent manner. However, the molecular mechanisms by which TRAFs control signaling function of these receptors remain obscure.
It is well known that TRAFs bind to the TNF receptor family molecules such as OX40 and control pro-inflammatory signaling in immune cells. Surprisingly, we have identified a novel anti-inflammatory function of TRAFs in the IL-6-receptor signaling. TRAF2 and TRAF5 bind to the signal transducing receptor gp130 and limit the pro-inflammatory activity in CD4+ T cells. We aim to understand novel and uncharacterized signaling functions of TRAFs and TNF-related molecules in the context of inflammatory and autoimmune diseases.

Understanding of molecular function and pathology of ABC protein subfamily D

ATP-binding cassette (ABC) protein subfamily D is composed of four family molecules, ABCD1 to ABCD4. We study the molecular mechanisms of substrate transport across membranes mediated by ABCD proteins in peroxisome and lysosome, and also analyze defective transporter activities of ABCD proteins in disease settings. Dysfunction of peroxisomal ABCD1 is responsible for X-linked adrenoleukodystrophy (X-ALD) that is characterized by the inflammation in the cerebrum and the progressive demyelination. We analyze the process of neurodegeneration in the brain that is driven by immune cells lacking expression of ABCD1.

Main research projects

  • 1. Regulation of pro-inflammatory cytokine signaling by TRAF family molecules
  • 2. Regulation of T cells by TNF-related family molecules
  • 3. Analysis of structure and function of ABC protein subfamily D
  • 4. Elucidation of molecular pathology of X-linked adrenoleukodystrophy and development of therapeutic agents