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MACKLIS LAB

Denis Jabaudon
Tina Lai

Arthur Czupryn

Liyun Li
Bartley Mitchell
Sanjay Magavi

Justine M. Nagurney

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MGH-HMS Center for Nervous System Repair
Macklis Lab

Noriyuki Kishi

Background

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.

Research Summary

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.

Publications (Original articles)

Kishi N, Tang Z, Maeda Y, Hirai A, Ito M, Suzuki S, Nakao K, Kinoshita T, Kadesch T, Hui C-c, Artavanis-Tsakonas S, Okano H, Matsuno K. Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis. Int. J. Devl. Neuroscience (2001) 19: 21-35.

Matsuno K, Ito M, Hori K, Miyasita F, Suzuki S, Kishi N, Artavanis-Tsakonas S, Okano H. Involvement of a proline-rich motif and a RING-H2 finger in a function of Deltex as a regulator of Notch signaling. Development (2002) 129: 1049-1059.

Yamamoto N, Yamamoto S, Matsunaga E, Kobayashi D, Torii M, Inagaki F, Kawaichi M, Fukamizu A, Kishi N, Matsuno K, Nakamura K, Okano H, Nakafuku M. Deltex mediates a Notch signaling targeting the transcriptional coactivator p300. J. Biol. Chem. (2001) 276: 45031-45040.

Asakawa S, Abe I, Kudoh Y, Kishi N, Wang Y, Kubota R, Kudoh J, Kawasaki K, Minoshima S, Shimizu N. BAC library: construction and rapid screening. Gene (1997) 191: 69-79.

Reviews

Kishi N, Okano H. "Isolation of neural stem cells" (Japanese), Noh-no-Kagaku (2003) suppl.: 36-41.

Kishi N, Macklis JD. "Neurogenesis in the adult mammalian brain" (Japanese), Igaku-no-Ayumi (2002) 201:313-317.

Kishi N, Okano H. "ES cells" (Japanese), Naika (2001) 88, 937-940.

Kishi N, Okano H. "Strategies of neural regenerartion using ES cells." (Japanese), Sanfujinka-no-Sekai (2001) 53:264-269.

Kishi N, Okano H. "Neural stem cells and its therapeutic application." (Japanese) Drug Delivery System (2001) 16: 23-28.

Kishi N, Okano H. "Isolation of neural stem cells and its clinical application." (Japanese) Noh-no-Kagaku (2001) 23: 111-117.

Kishi N, Okano H. "Common mechanisms of development in the nervous system from fly to mammalians." (Japanese) In The Brain and Neuron (Ishiura S eds.), pp62-69, Yohdosha, Tokyo, 1999.

Matsuno K, Ito M, Kishi N, Suzuki S, Artavanis-Tsakonas S, Okano H. "Physical and functional links between Deltex and Notch receptor in Drosophila melanogaster." In Neural Development (Uyemura K, Kawamura K, Yazaki T eds.), pp42-49, Springer Verlag, Tokyo, 1997

Abstracts

Kishi N, Macklis JD. "Neurobiological analysis of the role of MECP2 in differentiation and connectivity of cortical projection neurons." 33rd Society for Neuroscience in New Orleans (2003).

Kishi N, Macklis JD. "Neurobiological analysis of the role of MECP2 in differentiation and connectivity of cortical projection neurons: normal and MECP2 mutant mice." 4th Rett syndrome Symposium in Baltimore (2003).

Kishi N, Macklis JD. "The role of MECP2 in differentiation of cortical projection neurons." 32nd Society for Neuroscience in Orlando (2002).

Kishi N, Macklis JD. "The role of MECP2 in differentiation of cortical projection neurons." 3rd Rett syndrome Symposium in Baltimore (2002).

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