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Research

Control of HDL's Biological Activities

We have found that the biological activities (cholesterol efflux capacity, anti-inflammatory activities, etc.) of HDL are augmented by its genetic engineering, i.e., by fusing functional peptides to apoA-I. The mechanism of this augmentation and the methods for further augmentation through the comprehensive understanding of the structure-function relationship are under investigation.

 

Development of Therapeutically Active Nanocarriers on the Basis of HDL

Nascent form of HDL (nanodisc) can be prepared with various lipids and recombinant apoA-I protein or its mimetic peptides. We designated variously engineered nanodiscs as protein/peptide-rolled membrane discs (PMDs) and are developing PMDs as drug delivery nanocarriers. Our interest also focus on the development of lipid-free nanocarriers.

Development of the Assay Systems for Evaluating the Pharmacokinetics and Therapeutic Efficacy of Nanocarriers in Zebrafish

Zebrafish has been utilized as a vertebrate model in developmental biology research. Due to its availability in large number, its high physiological homologies with human and the optical transparency of its larvae, zebrafish is recently gaining attention as an efficient vertebrate model to enable the fast in vivo screening of nanocarriers functions with less cost and labor. In close joint research with Prof. Huwyler in Univ. of Basel, Switzerland, our effor is devoted to evaluation of the therapeutic potential of systemically or topically administered PMDs in zebrafish models of human diseases.

Restoring Vision with Donor-Acceptor-Linked Molecules (supported by JSPS Grant "Dynamic Excition")

Donor-acceptor-linked (D-A) molecules are photosensitizers in which a light harvester is sandwiched between an electron donor and an electron acceptor. Under visible light illumination, our D-A molecules yield a long-lived charge separeted state in it, which can be regarded as a "nano-electric field". We have reported that illuminated D-A molecules are capable of neuronal firing through decreasing the membrane potential (depolarization). In retinal ganglion cells in our retina, such neuronal firing following depolarization triggers visual transduction. By combining D-A molecules, synthesized by Prof. Imahori (Kyoto Univ.) and Prof. Sakuda (Nagasaki Univ.), and our nanocarriers, we are developing a novel therapy for restoring vision.

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(a) Gold nanorod (left) and carbon nanotubes (right).

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(a) Gold nanorod (left) and carbon nanotubes (right).