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Professor Hiroshi Hibino

Molecular and Cellular Pharmacology

The laboratory was founded in 1965 under Professor Sentaro Nagasaki. It has since been run by Professors Masayuki Okagawa, Toyoharu Imaizumi, Hiroshi Wada,Yoshihisa Kurachi and finally Hiroshi Hibino.

Clarifying the Logic of Organ Function from “Live” Local Phenomena Detected in Real Time

Each organ is made up of different tissues that stem from three-dimensional assemble of various cell types. Key questions in biology and medicine are how the organism function and how diseases are developed. To address this issue requires in vivo real-time detection of local phenomena that are elicited or affected by cells and integration of these measurements to events at tissues and organ levels. On the basis of such strategy, our group focuses on the study for the inner ear as well as drug pharmacokinetics. We are conducting unique research projects by means of state-of-the-art technologies that are developed and optimized through medicine-engineering collaboration. Among several approaches, “in vivo measurement” is crucial for our study.

1. Study for Cochlea of the Inner Ear in Mammals

Currently 5−10% of global population suffer from hearing loss. Particularly in developed countries including Japan, this figure is growing as a super-aging society steadily advances. Normal hearing is essential for people to have happy and fruitful lives. Hearing loss in the middle age leads to the greatest risk for dementia.

In order to overcome hearing loss, we intend to elucidate the mechanisms how the cochlea of the inner ear, a peripheral organ for hearing, works and to analyze the disease’s pathogenesis. The results and achievements would contribute to innovation of preventive medicine and pharmacotherapeutic interventions.

In the cochlea, sensory hair cells convert sound-driven vibrations to electrical signals, which are then transmitted to the brain. Together with supporting cells, the hair cells form a unique local space. Our group is working on the following four topics: (1) measuring in vivo the nanoscale vibration of the hair cells using a tomographic imaging system called “optical coherence tomography (OCT)”, which is constructed in collaboration with an engineer; (2) elucidating the “blueprint” of a cochlear biological battery that amplify sound signals by means of an electrophysiological sensor, as well as molecular biology, histology, and computational simulation; (3) analyzing the pathophysiology of deal animal models with the above approach; and (4) initiating a project to understand the relationship between hearing loss and cranial neuropathies such as dementia.

2. Research on Pharmacokinetics with Diamond sensor, an Advanced Material

A systemically administrated drug is delivered to all organs. Each organ is made up of a number of small cell populations that have different properties and roles. In many cases, some of these cell groups can be somehow affected, triggering a disease. To understand the desire and adverse reactions of a drug requires information whether the compound reached the target cell population and, when it has, how its “concentration” and “target cell function” will change over time. These indicators have not yet been fully measured by conventional methods. Therefore, we have developed a microsensing system that simultaneously measures the pharmacokinetics and pharmacodynamics of a drug in vivo. This real-time monitoring system consists of a “needle-type diamond microsensor”, which is an advanced electrochemical material developed by an engineer in Keio University.

Using this system, we are currently analyzing different drugs for the brain and inner ear. The results may explore regimens that maximize the efficacy of the drugs while suppressing adverse reactions, contribute to developing safe and effective drugs, and advance personalized medicine. We have also begun basic experiments to create a diamond sensor-based drug monitoring system that can be applied in clinical settings.