Hiroi Noboru, MD


Location: Med Rm. 211B


Cellular and Integrative Physiology, Cell Systems and Anatomy, & Pharmacology

Noboru Hiroi, Ph.D.


Personal Statement:

The primary aim of this laboratory is to more fully understand the genetic, cellular and molecular mechanisms of developmental neuropsychiatric disorders. Copy number variations (CNVs) are associated with high rates of autism spectrum disorder, intellectual disability, and schizophrenia.

Because CNVs include many individual genes, it is not possible to determine whether chromosomal segments or single genes are responsible for specific dimensional aspects of developmental neuropsychiatric disorders in humans. To circumvent this obstacle, our laboratory examines the role of chromosomal segments within CNVs and individual CNV-encoded genes in behavioral and cellular phenotypes in cell and mouse models.


1985 B.A. Waseda University, Tokyo, Japan
1991 Ph.D. McGill University, Montreal, Canada


  • Genetic
  • Cellular and molecular mechanisms underlying dimensional aspects of schizophrenia
  • Autism spectrum disorder
  • Intellectual disability

Awards & Accomplishments

2018              Fellow, ACNP
1986              Government of Canada Award
1986-1988    Bindra Pre-doctoral Fellowship
1991               Dean’s Honor List, McGill University
1992-1994    Human Frontier Science Program Fellow
1998              NARSAD Young Investigator Award
2006             NARSAD Independent Investigator Award
2007             Maltz NARSAD Investigator
2013              Elected Full Member of the American College of
Neuropsychopharmacology (ACNP)
2014              Elected Member of the Psychiatric Research Society
2016              Lilly Neuroscience Basic Research Award, International
College of Neuropyschopharmacology (CINP)
2018              Fellow, ACNP


Mai, L, Inada, H. Kimura, R., Kanno, K., Matsuda, T., Tachibana, R.O., Tucci, V., Komaki, F., Hiroi, N., Osumi,N.  Advanced paternal age diversifies individual trajectories of vocalization patterns in neonatal mice. iScience, in press, 2022.

Hiramoto, T., Boku, S., Kang,G., Abe, S., Barbachan e Silva, M., Tanigaki, K., Nagashima, M., Ye, K., Yamauchi, T., Michurina, T.V., Ó Broin, P., Enikolopov, G., Hiroi, N. Transcriptional regulation of neonatal neural stem cells is a determinant of social behavior. BioRxiv. 2021 https://www.biorxiv.org/content/10.1101/2021.11.12.468452v1.abstract

Hiramoto, T., Sumiyoshi, A.,  Yamauchi, T., Tanigaki, K., Shi, Q., Kang, G., Ryoke, R., Nonaka, H., Enomoto, S., Izumi, T., Bhat, M.A., Kawashima, R., Hiroi. N. Tbx1, a 22q11.2-encoded gene, is a link between alterations in fimbria myelination and cognitive speed in mice. Molecular Psychiatry “27, 929-93, 2022.” https://www.nature.com/articles/s41380-021-01318-4

Nakamura, M., Ye, K.,  Barbachan E Silva, M.,  Yamauchi, T., Hoeppner, D., Fayyazuddin, A., Kang, G., Yuda, E., Nagashima, M., Enomoto, S., Hiramoto, T., Sharp, R., Kaneko, I., Tajinda, K., Adachi, M., Mihara, T., Tokuno, S., Geyer, M., O’Broin, P., Matsumoto, M., Hiroi, N.  Computational identification of variables in neonatal vocalizations predictive for post-pubertal social behaviors in a mouse model of 16p11.2 deletion. Molecular Psychiatry  26 (11), 6578-6588, 2021.

Kato, R., Machida, A., Nomoto, K., Kang, G., Hiramoto, T., Tanigaki, K., Mogi, K., Hiroi, N, Kikusui, T., Maternal approach behaviors toward neonatal calls are impaired by mother’s experiences of raising pups with a risk gene variant for autism. Developmental Psychobiology. 63(1) 108-113, 2021

Yamauchi, T., Kang, G., Hiroi, N.  Heterozygosity of murine Crkl does not recapitulate behavioral dimensions of human 22q11.2 hemizygosity. Genes, Brain and Behavior. 20(5) e12719, 2021

Mikael Marttinen, M., Ferreira, CV., Paldanius, K., Takalo, M., Natunen, T., Mäkinen, P., Leppänen, L., Leinonen, V., Tanigaki, K., Kang, G., Hiroi, N., Soininen, H., Rilla, K., Haapasalo, A., Mikko Hiltunen, M. Presynaptic Vesicle Protein SEPTIN5 Regulates the Degradation of APP C-Terminal Fragments and the Levels of Aß. Cells. 9(11):2482, 2000

Zinkstok, J., Boot, E., Bassett, A., Hiroi, N., Butcher, N., Vingerhoets, C., Vorstman J., van Amelsvoort, T. The 22q11.2 deletion syndrome from a neurobiological perspective. Lancet Psychiatry 6 (11), 951-960, 2019.

Hiroi, N. and Yamauchi. T. Modeling and predicting developmental trajectories of neuropsychiatric dimensions associated with copy number variations. International Journal of Neuropsychopharmacology 22 (8), 488-500, 2019.

Ó Broin, P., Beckert, M. ,Takahashi, T., Nishi, A., Izumi, T., Kang, G., Pouso, P., Pena, J.L., Hiroi, N. Computational Analysis of Neonatal Mouse Ultrasonic Vocalization, Current Protocols in Mouse Biology Jun;8(2):e46, 2018.

Hiroi, N. Critical Reappraisal of Mechanistic Links of Copy Number Variants to Dimensional Constructs of Neuropsychiatric Disorders in Mouse Models. Psychiatry and Clinical Neuroscience. 72(5):301-321, 2018.

Boku, S, Izumi, T., Abe, S., Takahashi, T., Nishi, A., Naka, Y., Nomaru, H., Kang, G., Hishimoto, A., Duran-Torres, G., Tanigaki, K., Zhang, Z., Ye, K., K., Nagashima, M, Enomoto, S., Kato, S., Ma¨nnisto, P.,  Kobayashi, K., Mannisto, P. Hiroi, N. Copy number elevation of 22q11.2 genes arrests the developmental maturation of working memory capacity and adult neurogenesis. Molecular Psychiatry, 23, 985-992, 2018.

Esposito, G., Hiroi, N., Scattoni, M.L. Cry, baby, cry: Expression of distress as a biomarker and modulator in Autism Spectrum Disorder. International Journal of Neuropsychopharmacology (2017) 20(6):498-503.

Kikusui, T. and Hiroi, N.  A self-generated environmental factor as a potential contr’ibutor to atypical early social communication in autism. Neuropsychopharmacology 42(1), 378 (2017)Online published in December 2016.

Takahashi, T., Okabe, S., Ó Broin, P., Nishi, A., Ye, K., Beckert, M.V., Izumi, T.,  Machida, A., Kang, G., Pena, JL., Golden, A., Kikusui, K., Hiroi, N. Structure and function of neonatal social communication in a genetic mouse model of autism. Molecular Psychiatry. 21(9):1208-14, 2016.

Boku, S., Toda, H., Nakagawa, S, Kato, A., Inoue, T., Koyama, K., Hiroi, N.,  Kusumi, I. Neonatal maternal separation alters the capacity of adult neural precursor cells to differentiate into neurons via methylation of retinoic acid receptor gene promoter. Biological Psychiatry77(4) 335-344, 2015.

Hiroi, N. Small Cracks in the Dam: Rare genetic variants provide opportunities to delve into mechanisms of neuropsychiatric disorders. Biological Psychiatry 76(2):91-2, 2014.

Hiroi, N., Takahashi, T., Hishimoto, A., Izumi, A. Boku, S., Hiramoto, T.  Copy Number Variation at 22q11.2: from rare variants to common mechanisms of developmental neuropsychiatric disorders. Molecular Psychiatry 18: 1153-1165, 2013.

Harper, K.M., Hiramoto, T., Tanigaki, K., Kang, G., Suzuki, G., Trimble, W., Hiroi, N. Alterations of social interaction through genetic and environmental manipulation of the 22q11.2 gene Sept5 in the mouse brain. Human Molecular Genetics 21(15): 3489-3499, 2012.

Hiramoto, T., Kang, G., Suzuki, G., Satoh, Y., Kucherlapati, R., Watanabe, Y., Hiroi, N. Tbx1: identification of a 22q11.2 gene as a risk factor for autism spectrum disorder in a mouse model. Human Molecular Genetics, 20(24):4775-85 2011.

Suzuki, G.,  Harper,K.M., Hiramoto, T.,  Funke, B., Lee, M.S., Kang, G., Buell, M., Geyer, M.A.,  Kucherlapati, R., Morrow, B., Männistö, P.T., Agatsuma, S., Hiroi, N. Over-expression of a human chromosome 22q11.2 segment including TXNRD2, COMT, and ARVCF developmentally affects incentive learning and working memory in mice. Human Molecular Genetics,18(20):3914-25, 2009.

Suzuki,G., Harper, K., Hiramoto, T., Lee, M., Kang, G., Kinoshita, M., Tanigaki, M., Buell, M., Geyer, M., Trimble, W., Agatsuma, S., Hiroi, N. Sept5 deficiency exerts pleiotropic influence on social and affective behaviors and cognitive functions in mice. Human Molecular Genetics, 18(9):1652-60, 2009.

Hiroi N., Zhu H., Lee M., Funke B., Arai M., Itokawa M., Kucherlapati R., Morrow B., Sawamura T., Agatsuma S. A 200-kb region of human chromosome 22q11.2 confers antipsychotic-responsive behavioral abnormalities in mice. Proc. Natl. Acad. Sci. USA 102(52), 19132-19137, 2005.