Contact Information
423 Burrill Hall
407 South Goodwin Avenue
Urbana, IL 61801
Research Interests
Research Topics
Neurobiology, Synaptic Transmission, Learning and Memory
Disease Research Interests
Neurological and Behavioral Disorders
Research Description
Molecular mechanisms underlying excitability homeostasis and synaptic plasticity in health and disease
An imbalance in neuronal and synaptic excitability is a common abnormality observed in patients with various psychiatric and neurological disorders, including autism spectrum disorders, epilepsy and Alzheimer's disease. The dysregulation of excitability is thought to exacerbate disease symptoms. Identifying and understanding the mechanisms underlying the dysregulation of excitability could reveal novel therapeutic targets for these diseases. To achieve this goal, we utilize various approaches including molecular and cell biology, biochemistry, electrophysiology, and mouse genetics to understand the regulation of excitability homeostasis at synaptic, neuronal, network and system levels, and how the deficits of those affect behavior in diseases.
Current focuses of the lab include:
1. Studying activity-dependent translational control in fragile X syndrome
2. Exploring novel transcriptional and post-transcriptional regulators in neurodevelopment
3. Determining the role of cellular stress response in neuronal plasticity
4. Characterizing the molecular mechanisms contributing to comorbid seizures in Alzheimer's disease
Education
Postdoc 2010-2014 University of Texas Southwestern Medical Center, Dallas, TX
Ph.D. 2009 University of Minnesota, Minneapolis, MN
M.Sc. 2004 National Yang-Ming University, Taipei, Taiwan
B.S. 2002 National Taiwan University, Taipei, Taiwan
Awards and Honors
2020 James and Maxine Heath Excellence in Teaching Award
2019 Arnold O. Beckman Research Award
2016 - 2024 Teachers Ranked as Excellent
2015, 2018 NARSAD Young Investigator Award
2014 Simons Foundation Autism Initiative-Explorer Award
2011 National Research Service Award (NRSA) from NIH
2011 Meritorious Award at Postdoctoral Symposium at UTSW
2010 Dr. Marvin and Hadassah Bacaner Research Award, University of Minnesota
2008 Veneziale-Steer Research Award, University of Minnesota
2008 Milne Brandenberg Graduate Research Award, University of Minnesota
Additional Campus Affiliations
External Links
Highlighted Publications
Representative Publications
Kumar V, Lee KY, Acharya A, Babik MS, Christian-Hinman CA, Rhodes JS and Tsai NP (2024) mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS. EMBO Mol Med 16:506-522 [Link to paper]
Yook Y, Lee KY, Kim E, Lizarazo S, Yu X, and Tsai NP (2024) Hyperfunction of PSD-95 Promotes Seizure Response in Early-Stage Aβ Pathology. EMBO Rep 25:1233-1255 [Link to paper]
Lee KY, Wang H, Yook Y, Rhodes JS, Christian-Hinman CA, and Tsai NP (2023) Tumor Suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning. Molecular Psychiatry 28,3782–3794 [Link to paper] [News release]
Lizarazo S, Yook Y, and Tsai NP (2022) Amyloid beta induces Fmr1-dependent translational suppression and hyposynchrony of neural activity via phosphorylation of eIF2α and eEF2. J Cell Physiol 237:2929-2942 [Link to paper][News release]
Lodes DE, Zhu J, and Tsai NP (2022) E3 Ubiquitin Ligase Nedd4-2 Exerts Neuroprotective Effects During Endoplasmic Reticulum Stress. J Neurochem 160:613-624 [Link to paper]
Lee KY, Zhu J, Cutia CA, Christian-Hinman CA, Rhodes JS and Tsai NP (2021) Infantile spasms–linked Nedd4-2 mediates hippocampal plasticity and learning via cofilin signaling. EMBO Rep 22:e52645 [Link to paper][News release]
Liu DC, Lee KY, Lizarazo S, Cook JK and Tsai NP (2021) ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model. Neurobiol Dis 158, 105450 [Link to paper]
Eagleman DE, Zhu J, Liu DC, Seimetz J, Kalsotra A and Tsai NP (2020) Unbiased Proteomic Screening Identifies a Novel Role for the E3 Ubiquitin Ligase Nedd4-2 in Translational Suppression during ER Stress. J Neurochem 157:1809-1820 [Link to paper]
Liu DC, Soriano S, Yook Y, Lizarazo S, Eagleman DE and Tsai NP (2020) Chronic activation of Gp1 mGluRs leads to distinct refinement of neural network activity through non-canonical p53 and Akt signaling. eNeuro 7, 0438-19.2020 [Link to paper]
Liu DC, Eagleman DE and Tsai NP (2019) Novel Roles of ER Stress in Repressing Neural Activity and Seizures through Mdm2- and p53-dependent Protein Translation. PLOS Genet. 15(9):e1008364 [Link to paper][News release]
Zhu J, Lee KY, Jong TY and Tsai NP (2019) C2-lacking isoform of Nedd4-2 regulates excitatory synaptic strength through GluA1 ubiquitination-independent mechanisms. J Neurochem 151: 289-300 [Link to paper]
Lee KY, Jewett KA, Chung HJ and Tsai NP (2018) Loss of fragile X protein FMRP impairs homeostatic synaptic downscaling through tumor suppressor p53 and ubiquitin E3 ligase Nedd4-2. Hum Mol Genet. 27:2805–2816 [Link to paper][News release 1][News release 2]
Jewett KA, Lee KY, Eagleman DE, Soriano S and Tsai NP (2018) Dysregulation and restoration of homeostatic network plasticity in fragile X syndrome mice. Neuropharmacology 138:182-192 [Link to paper]
Liu DC, Seimetz J, Lee KY, Kalsotra A, Chung HJ, Lu H and Tsai NP (2017) Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural network activity. Hum Mol Genet. 26:3895–3908 [Link to paper]
Zhu J, Lee KY, Jewett KA, Man HY, Chung HJ and Tsai NP (2017) Epilepsy-associated gene Nedd4-2 mediates neuronal activity and seizure susceptibility through AMPA receptors. PLOS Genet. 13:e1006634 [Link to paper][Commentary][MCB News]
Jewett KA, Zhu J, and Tsai NP (2015) The tumor suppressor p53 guides GluA1 homeostasis through Nedd4-2 during chronic elevation of neuronal activity. J Neurochem 135:226-233
Wilkerson JR*, Tsai NP*, Maksimova MA, Wu H, Cabalo NP, Loerwald KW, Dictenberg JB, Gibson JR and Huber KM (2014). A role for dendritic mGluR5-mediated local translation of Arc/Arg3.1 in MEF2-dependent synapse elimination. Cell Rep 7:1589-1600 (*equal contribution)
Tsai NP*, Wilkerson, JR*, Guo, W, Maksimova, MA, DeMartino, GN, Cowan CW and Huber KM (2012) Multiple autism-linked genes mediate synapse elimination via proteasomal degradation of a synaptic scaffold PSD-95. Cell 151: 1581-1594 (*equal contribution)
Tsai NP, Lin YL, Tsui YC, Wei LN (2010) Dual action of epidermal growth factor: extracellular signal-stimulated nuclear-cytoplasmic export and coordinated translation of selected messenger RNA. J Cell Biol 188: 325-333.
Tsai NP, Tsui YC, Pintar JE, Loh HH, Wei LN (2010) Kappa opioid receptor contributes to EGF- stimulated neurite extension in development. Proc Natl Acad Sci U S A 107: 3216-3221.
Tsai NP, Ho PC, Wei LN (2008) Regulation of stress granule dynamics by Grb7 and FAK signalling pathway. EMBO J 27: 715-726.
Tsai NP, Bi J, Wei LN (2007) The adaptor Grb7 links netrin-1 signaling to regulation of mRNA translation. EMBO J 26: 1522-1531.
Recent Publications
Kumar, V., Lee, K. Y., Acharya, A., Babik, M. S., Christian-Hinman, C. A., Rhodes, J. S., & Tsai, N. P. (2024). mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS. EMBO Molecular Medicine, 16(3), 506-522. https://doi.org/10.1038/s44321-024-00038-w
Mehta, K., Yentsch, H., Lee, J., Yook, Y., Lee, K. Y., Gao, T. T., Tsai, N. P., & Zhang, K. (2024). Phosphatidylinositol-3-phosphate mediates Arc capsid secretion through the multivesicular body pathway. Proceedings of the National Academy of Sciences of the United States of America, 121(35), Article e2322422121. https://doi.org/10.1073/pnas.2322422121
Mitra, A., Deats, S. P., Dickson, P. E., Zhu, J., Gardin, J., Nieman, B. J., Mark Henkelman, R., Tsai, N. P., Chesler, E. J., Zhang, Z. W., & Kumar, V. (2024). Tmod2 Is a Regulator of Cocaine Responses through Control of Striatal and Cortical Excitability and Drug-Induced Plasticity. Journal of Neuroscience, 44(18), Article e1389232024. https://doi.org/10.1523/JNEUROSCI.1389-23.2024
Yook, Y., Lee, K. Y., Kim, E., Lizarazo, S., Yu, X., & Tsai, N. P. (2024). Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology. EMBO Reports, 25(3), 1233-1255. https://doi.org/10.1038/s44319-024-00090-0
Lee, K. Y., Wang, H., Yook, Y., Rhodes, J. S., Christian-Hinman, C. A., & Tsai, N. P. (2023). Tumor suppressor p53 modulates activity-dependent synapse strengthening, autism-like behavior and hippocampus-dependent learning. Molecular Psychiatry, 28(9), 3782-3794. https://doi.org/10.1038/s41380-023-02268-9
