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MEF2C enhances dopaminergic neuron differentiation of human embryonic stem cells in a parkinsonian rat model.
Cho EG, Zaremba JD, McKercher SR, Talantova M, Tu S, Masliah E, Chan SF, Nakanishi N, Terskikh A, Lipton SA
PLoS One. 2011;6(8):e24027
Excitatory glycine responses of CNS myelin mediated by NR1/NR3 "NMDA" receptor subunits.
Piña-Crespo JC, Talantova M, Micu I, States B, Chen HS, Tu S, Nakanishi N, Tong G, Zhang D, Heinemann SF, Zamponi GW, Stys PK, Lipton SA
J Neurosci. 2010 Aug 25;30(34):11501-5
Neuroprotection by the NR3A subunit of the NMDA receptor.
Nakanishi N, Tu S, Shin Y, Cui J, Kurokawa T, Zhang D, Chen HS, Tong G, Lipton SA
J Neurosci. 2009 Apr 22;29(16):5260-5
Modulation of NMDA receptor properties and synaptic transmission by the NR3A subunit in mouse hippocampal and cerebrocortical neurons.
Tong G, Takahashi H, Tu S, Shin Y, Talantova M, Zago W, Xia P, Nie Z, Goetz T, Zhang D, Lipton SA, Nakanishi N
J Neurophysiol. 2008 Jan;99(1):122-32
Takusan: a large gene family that regulates synaptic activity.
Tu S, Shin Y, Zago WM, States BA, Eroshkin A, Lipton SA, Tong GG, Nakanishi N
Neuron. 2007 Jul 5;55(1):69-85
A developmental influence of the N-methyl-D-aspartate receptor NR3A subunit on prepulse inhibition of startle.
Brody SA, Nakanishi N, Tu S, Lipton SA, Geyer MA
Biol Psychiatry. 2005 May 15;57(10):1147-52
Excitatory glycine receptors containing the NR3 family of NMDA receptor subunits.
Chatterton JE, Awobuluyi M, Premkumar LS, Takahashi H, Talantova M, Shin Y, Cui J, Tu S, Sevarino KA, Nakanishi N, Tong G, Lipton SA, Zhang D
Nature. 2002 Feb 14;415(6873):793-8
Neurotrophins, but not depolarization, regulate substance P expression in the developing optic tectum.
Tu S, Debski EA
J Neurobiol. 2001 Aug;48(2):131-49
Activity-dependent regulation of substance P expression and topographic map maintenance by a cholinergic pathway.
Tu S, Butt CM, Pauly JR, Debski EA
J Neurosci. 2000 Jul 15;20(14):5346-57
Development and regulation of substance P expression in neurons of the tadpole optic tectum.
Tu S, Debski EA
Vis Neurosci. 1999 Jul-Aug;16(4):695-705
Shichun Tu's Research Focus
Alzheimer's Disease, Autism Spectrum Disorders
Dr. Tu has found that α1-takusan increases neuronal synaptic activity and in doing so mitigates synaptic damages caused by the accumulation of Aβ peptides, a primary pathology leading to memory loss and cognitive dysfunctions in Alzheimer’s disease (AD). Based on these findings, Dr. Tu is currently exploring the potential therapeutic benefits of this protein in the treatment of AD.
Dr. Tu has also established an animal model of autism-spectrum disorders (ASD) using mice heterozygous for Mef2c, an important transcription factor in neuronal development. These mice mimic ASD in human patients who only carry one copy of the MEF2C gene (MEF2C haploinsufficiency). Using these mice, he is attempting to understand the molecular and cellular deficits underlying the pathogenesis of ASD and evaluate the effectiveness of various drug treatments.
Shichun Tu's Research Report
Takusan family members protect against Aβ-induced synaptic dysfunction
Using microarray technology, Dr. Tu identified a large family of genes that he has named takusan (meaning “many” in Japanese). Takusan family members are proteins capable of increasing neuronal synaptic activity (Tu et al., 2007 Neuron). Dr. Tu reasoned that takusan mediated elevation of synaptic activity may be able to counteract the deleterious effects of pathogenic Aβ peptides. Indeed, his investigation ascertained that forced expression of takusan proteins in cultured hippocampal neurons alleviates synaptic degeneration induced by Aβ oligomers. He further determined that the protective effects of takusan are mediated by its interaction with the proteins PSD-95 and tau at postsynaptic sites. Currently, Dr. Tu’s research focuses on the therapeutic potential of takusan in the treatment of AD. To this end, he has generated truncated takusan constructs (~51 aa long) that retain their ability to protect against Aβ oligomers. He is currently working to exploit this finding by developing takusan-based agents for the treatment of AD in humans.
Modeling autism-spectrum disorders (ASD) using genetically modified mice
Rett syndrome (RTT) is a type of ASD caused by mutations in the X-linked MECP2 gene. MECP2 is a transcription factor that regulates expression of MEF2C, a transcription factor important for neuronal development. Recently, a heterozygous deletion of the MEF2C gene has been associated with autistic-like symptoms in human patients. Dr. Tu leads a multi-center research initiative involving scientists from Sanford-Burnham, Scripps, and UCSD to establish an animal model of ASD based on MEF2C haploinsufficiency. Using a combination of behavioral, biochemical, and electrophysiological analyses coupled with state-of-the-art Confocal imaging and Aperio scanning technology, Dr Tu and his colleagues have identified molecular deficits in synaptic functions in MEF2C heterozygous mice. Current endeavors focus on drug screening in MEF2C deficient animals to mitigate neurological deficits reminiscent of ASD. Collectively, these studies not only provide molecular insights into the pathogenesis of ASD, but may also lead to the identification novel disease modifying therapies.