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
Imbalances in neuronal and synaptic excitability are hallmark features of numerous neurological and psychiatric disorders, including autism spectrum disorders, epilepsy, and Alzheimer's disease. Dysregulated excitability is believed to contribute directly to disease progression and symptom severity by disrupting the normal function of neural circuits. A deeper understanding of the mechanisms that maintain excitability homeostasis is therefore essential for identifying novel therapeutic strategies. To address this challenge, our research integrates molecular and cellular biology, biochemistry, electrophysiology, and mouse genetics to investigate how excitability is regulated across multiple levels of neural organization, from individual synapses and neurons to complex neural networks and brain systems. By elucidating the cellular and molecular pathways that preserve excitability homeostasis, and determining how their disruption alters neural function and behavior, our work aims to uncover fundamental mechanisms underlying brain disorders and identify potential targets for therapeutic intervention.
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
2010-2014 Postdoc University of Texas Southwestern Medical Center, Dallas, TX
2009 Ph.D. University of Minnesota, Minneapolis, MN
2004 M.Sc. National Yang-Ming University, Taipei, Taiwan
2002 B.S. 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
Wang S, Yook Y, Lizarazo S, Lee KY, VanBortle K, Christian-Hinman CA, Rhodes JS and Tsai NP (2026) ATF4 modulates Group 1 mGluR-dependent molecular signaling, hippocampal plasticity, and behavior. Molecular Psychiatry (in press)
Pan M, Acharya A, Lee KY, Rhodes JS and Tsai NP (2026) Hyperfunction of PSD-95 leads to hyperexcitability and cognitive abnormalities in MEF2C haploinsufficiency. Proc Natl Acad Sci U S A (in press)
Acharya A, Kumar V, Lee KY, Babik MS, Goswami G, Boateng KA, Cyphersmith AJ, Rhodes, JS, Tsai NP (2026) Reversing Pathophysiology in Fragile X Syndrome Mice by Promoting PGC-1α and Mitochondrial Functions. bioRxiv [Link to Preprint]
Wang Y, Zhu J, Lizarazo S, Lee KY, Wong O, Azim S, Yook Y, Kumar V, Tsai NP (2026) E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-induced Mitochondrial Defects in an Alzheimer’s Disease Mouse Model. J Neurochem [Link to Paper]
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]
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, 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]
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]
Recent Publications
Wang, Y., Zhu, J., Lizarazo, S., Lee, K. Y., Wong, O., Azim, S., Yook, Y., Kumar, V., & Tsai, N. P. (2026). E3 Ubiquitin Ligase Nedd4-2 Exacerbates Seizure-Induced Mitochondrial Defects in an Alzheimer's Disease Mouse Model. Journal of Neurochemistry, 170(4), Article e70440. https://doi.org/10.1111/jnc.70440
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
