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).