He did postdoctoral fellowships at the University of California San Diego and the University of California San Francisco. He also served on the faculty at Osaka City University School of Medicine in Japan. He was appointed to the faculty in the Department of Neurobiology & Anatomy at the College of Medicine in 2013. - See more at: http://www.drexelmed.edu/Home/AboutOurFaculty/KazuhitoToyooka.aspx#sthash.a5rQ7400.dpuf

Current lab personnel:

• Sara Blajezewski, PhD candidate
• Sarah Bennison, PhD candidate
• Xiaonan Liu, PhD candidate

Past lab personnel:

• Trevor Smith, research assistant
• Brett T. Cornell, PhD
• Tomoka Wachi, PhD, postdoctoral fellow
• Thomas Sibert, MD student
• Courtney Marshall, PhD candidate

Our lab has been studying the mechanisms of cerebral cortical development with a specific focus on neuronal migration and morphogenesis related to behavioral disorders such as autism spectrum disorder (ASD). To uncover the mechanisms involved in these processes, we have created and analyzed many novel mouse models with genetic modifications by utilizing a wide range of techniques including mouse genetics, in utero electroporation, time-lapse live imaging in vitro and on brain slices, and CRISPR/Cas9.

After migrating post-mitotic neurons reach the cortical plate in the cerebral cortex, neurons start establishing neuronal circuits. To accomplish this, neurite initiation is followed by the extension of neurites, which eventually develop into dendrites and an axon. There is no doubt that cytoskeletal proteins including actin, microtubules, and associated binding proteins are important for neurite initiation and extension. However, the precise mechanisms of neurite formation, and particularly neurite initiation, have not been clarified. Defects in neurite formation cause improper neural circuit formation, which has been implicated in neurological diseases such as ASD. Our goals are to decipher the mechanisms of neuronal morphogenesis that are required to form appropriate neuronal connections and to clarify the underlying molecules and mechanisms in this cellular process.

Ongoing Projects

• Analysis of the mechanisms of neuronal morphogenesis, such as neurite formation and synaptogenesis, in the cerebral cortex
• Understanding of the etiology of Lissencephaly/Miller Dieker syndrome
• Analysis of the functions of the 14-3-3 family of proteins in behavior with respect to human mental illnesses such as autism and schizophrenia

Preprints

"High-Throughput Kinase Inhibitor Screening Reveals Roles for Aurora and Nuak Kinases in Neurite Initiation and Dendritic Branching."
Blazejewski SM, Bennison SA, Liu X. and Toyo-oka K
BioRxiv. 2020.06.25.162271 [Preprint]. June 26, 2020.

"14-3-3 shuttles activity-dependent neuroprotective protein to the cytoplasm to promote appropriate neuronal morphogenesis, cortical connectivity and calcium signaling."
Bennison SA, Blazejewski SM, Liu X and Toyo-oka K
BioRxiv. 2020.05.26.105015 [Preprint]. May 27, 2020

"Glutathione S-transferase Pi (Gstp) Proteins Regulate Neuritogenesis in the Developing Cerebral Cortex."
Liu X, Bennison SA, Blazejewski SM and Toyo-oka K
BioRxiv. 2020.01.06.895672 [Preprint]. May 22, 2020

"PEDF-Rpsa-Itga6 signaling regulates cortical neuronal morphogenesis."
Blazejewski SM, Bennison SA, Ha NY, Liu X, Smith TH, Dougherty KJ, and Toyo-oka K
BioRxiv. 2020.01.06.895672 [Preprint]. April 13, 2020

Peer-Reviewed Manuscripts

"Methionine sulfoxide reductase A (MsrA) mediates the ubiquitination of 14-3-3 protein isotypes in brain."
Deng Y, Jiang B, Rankin CL, Toyo-Oka K, Richter ML, Maupin-Furlow JA, Moskovitz
J. Free Radic Biol Med. 2018, 129: 600-607.

"Complete ablation of the 14-3-3epsilon protein results in multiple defects in neuropsychiatric behaviors."
Wachi T, Cornell B and Toyo-oka K
Behav Brain Res, 2017, 319: 31-36.

" In vitro and in vivo Analysis of 14-3-3epsilon and the Regulation of Neuronal Morphogenesis via the Microtubule Binding Protein, Doublecortin."
Cornell B, Wachi T, Zhukarev V and Toyo-oka K
Hum Mole Genet, 2016, 25(20): 4405-4418.

"Overexpression of the 14-3-3Gamma Protein in Embryonic Mice Results in Neuronal Migration Delay in the Developing Cerebral Cortex"
Cornell B, Wachi T, Zhukarev V and Toyo-oka K
Neurosci Lett, in press, doi:10.1016/j.neulet.2016.06.009.

"Deficiency of 14-3-3ε and 14-3-3ζ by the Wnt1 promoter-driven Cre recombinase results in pigmentation defects"
Cornel B and Toyo-oka K
BMC Res Notes, 9(1);180-185, 2016

"Ablation of the 14-3-3gamma Protein Results in Neuronal Migration Delay and Morphological Defects in the Developing Cerebral Cortex"
Wachi T, Cornell B, Marshall C, Zhukarev V, Baas PW, and Toyo-Oka K
Dev Neurobiol., 76 (6): 600-614, 2016

"14-3-3epsilon and zeta Regulate Neurogenesis and Differentiation of Neuronal  Progenitor Cells in the Developing Brain""
Toyo-oka K, Wachi T, Hunt RF, Baraban SC, Taya S, Ramshaw H, Kaibuchi K,  Schwarz QP, Lopez AF and Wynshaw-Boris A
J Neurosci., 34(36):12168-12181, 2014

"14-3-3{varepsilon} Plays a Role in Cardiac Ventricular Compaction by Regulating the Cardiomyocyte Cell Cycle"
Kosaka Y, Cieslik KA, Li L, Lezin G, Maguire CT, Saijoh Y, Toyo-Oka K, Gambello MJ, Vatta M, Wynshaw-Boris A, Baldini A, Yost HJ and Brunelli L
Mol. Cell. Biol., 32:5089-5102, 2012

"Neurodevelopmental defects and neuropsychiatric behaviour arise from 14-3-3zeta deficiency"
Cheah PS, Ramshaw HS., Thomas PQ, Toyo-oka K, Martin S, Coyle P, Guthridge MA, Stomski F, van den Buuse M, Wynshaw-Boris A, Lopez AF and Schwarz QP
Mol. Psychiatr., 17:451-466, 2011

"Identification of YWHAE, a gene encoding 14-3-3epsilon, as a possible susceptibility gene for schizophrenia"
Ikeda M, Hikita T, Taya S, Uraguchi-Asaki J, Toyo-oka K, Wynshaw-Boris A, Ujike H, Inada T, Takao K, Miyakawa T, Osaki N, Kaibuchi K and Iwata N
Hum. Mol. Genet., 17: 3212-3222, 2008

"A Neuroepithelial Stem Cell Proliferation requires LIS1 for Precise Spindle Orientation and Symmetric Division"
Yingling J, Youn YH, Darling D, Toyo-oka K, Pramparo T, Hirotsune S and Wynshaw-Boris
Cell, 132: 474-486, 2008

"Protein Phosphatase4 catalytic subunit (PP4c) regulates CDK1 activity and organization of microtubules through dephosphorylation of NDEL1"
Toyo-oka K, Yano Y, Shiota M, Iwao H, Hiraiwa N, Muramatsu M, Yoshiki A and Hirotsune S
J Cell Biol., 180: 1133-1147, 2008

"NDEL1 Phosphorylation by Aurora-A Kinase Is Essential for Centrosomal Maturation, Separation, and TACC3 recruitment"
Mori D, Yano Y, Toyo-oka K, Yoshida N, Yamada M, Muramatsu M, Zhang D, Saya H, Toyoshima YY, Kinoshita K, Wynshaw-Boris A and Hirotsune S
Mol. Cell. Biol., 27: 352-367, 2007

"Mnt-Deficient Mammary Glands Exhibit Impaired Involution and Tumors with Characteristics of Myc Overexpression"
Toyo-oka K, Bowen TJ, Hirotsune S, Li Z, Jain S, Ota S, Lozach LE, Bassett IG, Lozach J, Rosenfeld MG, Glass CK, Eisenman R, Ren B, Hurlin PJ and Wynshaw-Boris A
Cancer Res., 66: 5565-5573, 2006

"Recruitment of katanin P60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration"
Toyo-oka K, Sasaki S, Yano Y, Mori D, Kobayashi T, Toyoshima YY, Tokuoka SM, Ishii S, Shimizu T, Muramatsu M, Hiraiwa N, Yoshiki A, Wynshaw-Boris A and Hirotsune S
Hum. Mol. Genet., 14: 3113-3128, 2005

"Complete Loss of Ndel1 Results in Neuronal Migration Defects and Early Embryonic Lethality"
Sasaki S, Mori D, Toyo-oka K, Chen A, Garrett-Beal L, Muramatsu M, Miyagawa S, Hiraiwa N, Yoshiki A, Wynshaw-Boris A, and Hirotsune A
Mol. Cell. Biol., 25:7812-7827, 2005

"Loss of the Max-interacting protein Mnt in mice results in decreased viability, defective embryonic growth and craniofacial defects: relevance to Miller-Dieker syndrome"
Toyo-oka K, Hirotsune S, Gambello MJ, Zhou Z-Q, Olson L, Rosenfeld MG, Eisenman R, Hurlin PJ and Wynshaw-Boris A
Hum. Mol. Genet., 13:1057-1067, 2004

"Evidence of Mnt-Myc Antagonism Revealed by Mnt Gene Deletion"
Hurlin PJ, Zhou Z-Q, Toyo-oka K, Ota S, Walker WL, Hirotsune S and Wynshaw-Boris A
Cell Cycle, 3:97-99, 2004

"Deletion of Mnt leads to disrupted cell cycle control and tumorigenesis"
Hurlin PJ, Zhou Z-Q, Toyo-oka K, Ota S, Walker WL, Hirotsune S and Wynshaw-Boris A
EMBO J., 22:4584-4596, 2003

"14-3-3epsilon is important for neuronal migration via binding of NUDEL : a molecular explanation for Miller-Dieker syndrome"
Toyo-oka K, Shionoya A, Gambello MJ, Cardoso C, Leventer R, Ward HL, Ayala R, Tsai L-H, Dobyns W, Ledbetter D, Hirotsune S and Wynshaw-Boris A
Nat. Genet., 34:274-285, 2003

"Refinement of a 400-kb Critical Region Allows Genotypic Differentiation between Isolated Lissencephaly, Miller-Dieker Syndrome, and Other Phenotypes Secondary to Deletions of 17p13.3"
Cardoso C, Leventer RJ, Ward HL, Toyo-oka K, Chung J, Gross A, Martin CL, Allanson J, Pilz DT, Olney AH, Mutchinick OM, Hirotsune S, Wynshaw-Boris A, Dobyns WB and Ledbetter DH
Am. J. Hum. Genet., 72:918-930, 2003

Reviews

"Protein kinases: master regulators of neuritogenesis and therapeutic targets for axon regeneration."
Bennison SA, Blazejewski SM, Smith TH, Toyo-oka K
Cell Mol Life Sci. (2019) Oct 28. doi: 10.1007/s00018-019-03336-6

"Neurodevelopmental Genetic Diseases Associated with Microdeletions and Microduplications of Chromosome 17p13.3"
Blajezewski SM, Bennison SA, Smith TH and Toyo-oka K
Front. Genet. 9:80 (2018) doi: 10.3389/fgene.2018.00080

"14-3-3 proteins in brain development: neurogenesis, neuronal migration and neuromorphogenesis."
Cornell B and Toyo-oka K
Front. Mol. Neurosci, 2017, 12 October 2017, https://doi.org/10.3389/fnmol.2017.00318v

"Novel Functions of 14-3-3 Proteins in Neurogenesis and Neuronal Differentiation In Vivo."
Wachi T and Toyo-oka K
Ther Targets Neurol Dis (Therapeutic targets for neurological diseases), 2015, 2(1), doi: 10.14800/ttnd.500

"Miller-Dieker Syndrome: Analysis of a Human Contiguous Gene Syndrome in the Mouse"
Yingling J, Toyo-oka K, and Wynshaw-Boris A
Am. J. Hum. Genet., 73(3):475-488, 2003