1)  Demyelinating disease

Myelin is a multilayered sheath wrapped around axons that is important for rapid action potential conduction, survival, and metabolic support. Various factors of genetic, immunological, and environmental origins can disrupt myelin structures and impair normal signal transduction, ultimately resulting in neurodegeneration. Multiple sclerosis (MS) is the most common demyelinating disease of the CNS. It is thought to be caused by the immune system inappropriately attacking myelin in the brain and spinal cord, resulting in the demyelination of axons. Although immunomodulators are being used for therapy, there is no drug for promoting remyelination. Therefore, we are trying to reveal the myelination process in vivo and to find new drug candidates for the improvement of remyelination.

2)  Oligodendrocyte(OL) dysfunction in neurodegenerative disease

Neurodegenerative disease has a complex pathophysiological mechanisms that contribute to phenotype. Although neuronal degeneration is a hallmark pathological feature, it isnow widely recognized that neighboring glial cells contribute to neuronal degeneration. Particuarly, oligodendrocyte dysfunction and myelin damage is considered to be a major contributing factor to neurodegeneration in several neurodegenerative disease such as amyotrophic lateral sclerosis (ALS), Parkinson disease and multiple system atrophy(MSA). To investigate the role of oligodendrocytes and myelin in pathogenesis, we generated humanized transgenic zebrafish and examined the pathological features and effects on neuronal degeneration.

More than 4 million people worldwide have rare disease and most rare diseases usually caused by genetic variation. To make the right diagnosis for the right treatment, it is important to identify the disease-causing genes. However, it can be difficult to predict disease-causing variant because many human disorders are caused by complex genetics involving combinations of low-penetrant genetic variants. Therefore, we are trying to generate zebrafish model using precise genome-editing for validation of disease-causing variants and investigation of pathological mechanisms.

Neurotoxicity means that biological, chemical, and physical agents adversely affect the structure or function of nervous systems. Zebrafish has become a popular model for both environmental and chemical toxicity assessments. We investigate and evaluate neurotoxic effects of chemicals using zebrafish. We are conducting behavioral analysis and image analysis for accurate neurotoxicity evaluation. 

Zebrafish is a powerful ‘model’ organism for disease and translational research. Zebrafish share much of the physiology and anatomy with humans and other vertebrates, and many of the disease processes of the zebrafish directly model clinical disease and outcome. Based on collaboration with MD clinician, we are generating zebrafish model that mimics various human diseases, and we are looking for ways how to understand and treat human disease.