(1) Multi functional peptide Pituitary adenylate cyclase-activating polypeptide (PACAP)
PACAP, a pleiotropic neuropeptide, was first isolated from ovine hypothalamus based on its ability to stimulate adenylate cyclase in cultured rat anterior pituitary cells. PACAP is highly homologized to vasoactive intestinal polypeptide, categorized in secretin-glucagon family. PACAP lead depressor activity, vascular relaxation (on circulatory organ), secretion of catecholamine (on adrenal medulla) and positive inotropic action (on heart). In the brain cells PACAP affect not only pituitary neurons but also neurons from other brain region or astrocyte, leading to progression of neurite and suppression for neuronal death mediated by glutamate or brain stroke. Thus, we are focusing on 4 points shown below.
- Developing medicine against brain stroke in clinical therapy. We are focusing on indirect effect to protect neurons by PACAP via astrocyte or vascular cells which are also damaged by brain ischemia.
- To understand the translation mechanism of PACAP specifically in neurons through observation of cis-element on 5’ franking region of PACAP. associated with neuro-specific silencer
- Investigation of activity or ligand affinity on 4 splice-variants of PAC1 receptor.
- Physiological importance of PACAP on pain signaling.
(2) Orphan G-protein coupled receptors (GPCR)
GPCR having 7 trans membrane domains make greatest family in receptors, containing about 1000 families, in which 150 species of GPCR have not been identified their endogenous ligands. Such receptor is called orphan receptor.
- We are investigating GPCR for lipid expressed in circulatory system to understand a function on arterial sclerosis.
- We are identifying ligands of orphan receptors expressed in neurons to understand a signaling mechanism for generation, differentiation and live.
(3) Pharmacological genomics and proteomics
Global screening of how to effect on medicine to central nerves system.
(4) Develop a model of lifestyle disease on monkeys.
How do you know the effect of medicine on mice really occurred also in human being? The research of developing medicine and understanding pathology should be done in primates. Thus, we are making the model for diabetes, hyper-tension and arterial sclerosis with common marmoset. Marmoset propagates rapidly and treats easily compare to the other primates. Recently, the transgenic marmoset has been constructed by group belonged in Keio University. Therefore, marmoset will be paid more attention from now. We have a one of biggest colony for common marmoset and propagate by ourselves.