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Nien-Pei Tsai

Profile picture for Nien-Pei Tsai

Contact Information

Department of Molecular and Integrative Physiology
423 Burrill Hall
407 South Goodwin Avenue
Urbana, IL 61801
Associate Professor of Molecular & Integrative Physiology

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


B.S. 2002 National Taiwan University, Taipei, Taiwan
M.Sc. 2004 National Yang-Ming University, Taipei, Taiwan
Ph.D. 2009 University of Minnesota, Minneapolis, MN
Postdoc 2010-2014 University of Texas Southwestern Medical Center, Dallas, TX

Awards and Honors

2020 James and Maxine Heath Excellence in Teaching Award
2019 Arnold O. Beckman Research Award
2016 - 2023 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

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.

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.

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.

Baculis, B. C., Kesavan, H., Weiss, A. C., Kim, E. H., Tracy, G. C., Ouyang, W., Tsai, N. P., & Chung, H. J. (2022). Homeostatic regulation of extracellular signal-regulated kinase 1/2 activity and axonal Kv7.3 expression by prolonged blockade of hippocampal neuronal activity. Frontiers in Cellular Neuroscience, 16, Article 838419.

Liu, X., Kumar, V., Tsai, N. P., & Auerbach, B. D. (2022). Hyperexcitability and Homeostasis in Fragile X Syndrome. Frontiers in Molecular Neuroscience, 14, Article 805929.

View all publications on Illinois Experts

In the news

  • A surge of a neural-specific protein in the brain is the earliest-yet biomarker for Alzheimer’s disease, report University of Illinois Urbana-Champaign researchers studying a mouse model of the disease. Furthermore, the increased protein activity leads to the seizures associated with the earliest...
  • Fragile X syndrome is one of the most commonly inherited forms of autism and intellectual disability, and no treatment currently exists. But a team of University of Illinois researchers led by Vipendra Kumar, a postdoctoral researcher in the Department of Molecular & Integrative Physiology, has...
  • University of Illinois researchers have established the protein p53 as critical for regulating sociability, repetitive behavior, and hippocampus-related learning and memory in mice, illuminating the relationship between the protein-coding gene TP53 and neurodevelopmental and psychiatric disorders...
  • In recognition of his work, Dr. Vipendra Kumar was recently awarded a fellowship from the FRAXA Research Foundation, whose mission is to discover better treatments and ultimately cure the genetic disorder Fragile X Syndrome.
  • A new study by researchers at the University of Illinois Urbana-Champaign suggests the overexpression of a particular gene could serve as a risk factor for Alzheimer’s disease. Their findings could also lead to better understandings of the links between Alzheimer’s disease, Fragile X Syndrome, and...