Research Overview

My research career goal is to contribute to the understanding and treatment of human neurological disease, especially neurodevelopmental and neurodegenerative disease. Specifically, many neurodevelopmental and neurodegenerative diseases are possible to diagnose, but currently

impossible to treat effectively. After I received my M.D. degree at Keio University School of Medicine in Tokyo, I entered the Ph.D. course at Osaka University Graduate School of Medicine. While I spent my Ph.D. course in Osaka, neural stem cell research had been progressing rapidly. As I thought neural stem cell approaches might provide a breakthrough for the treatment of neurological diseases, I joined the Macklis lab as a postdoctoral fellow in 2001.

My current research interests lie in the neurobiological understanding of the role of the methyl-CpG binding protein 2 (MECP2) in the central nervous system (CNS). Rett syndrome is a neurodevelopmental disorder and one of the causes of mental retardation and autistic behavior primarily in girls, but also in a small group of boys. In 1999, it was discovered that mutation of MECP2 gene encoding a transcriptional repressor on the X chromosome causes Rett syndrome. Although it is evident that phenotypes of MECP2 mutant mice and symptoms of Rett syndrome are attributable to lack of the MECP2 gene in the CNS, there is little neuropathological understanding of the abnormalities in the CNS of MECP2-null mice as well as of patients with Rett syndrome. Therefore, I am investigating the neuropathological events in

MECP2-null mice using histological, molecular biological, and cell culture techniques, hoping that my study will not only add to our understanding of molecular mechanisms of MECP2 and pathological mechanisms of Rett syndrome, but will potentially contribute to the development of future therapeutic strategies for patients with Rett syndrome.

Key Recent Publications

• Kishi N, Macklis JD. MECP2 is progressively expressed in post-migratory neurons and is involved in neuronal maturation rather than cell fate decisions. Mol Cell Neurosci (2004) 27: 306-321.
• Kishi N, Macklis JD. Dissecting MECP2 function in the CNS. J Child Neurol (2005) 10:753-759.
• Kishi N, Macklis JD. "Neurogenesis in the adult mammalian brain" (Japanese), Igaku-no-Ayumi (2002) 201:313-317.