423A Burrill Hall
Office: (217) 244-5620
Fax: (217) 333-1133
Mail to: Department of Molecular and Integrative Physiology
524 Burrill Hall
407 South Goodwin Avenue,
Urbana, IL 61801
Development, Neurobiology, Signal Transduction, Synaptic Transmission
Disease Research Interests
Neurological and Behavioral Disorders
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
Molecular mechanisms underlying excitability homeostasis 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 schizophrenia and bipolar, mood disorders, epilepsy and autism spectrum disorders. Identifying and understanding the mechanisms underlying the regulation of excitability will potentially reveal novel therapeutic targets for these diseases. My laboratory utilizes 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. Two particular areas in which my laboratory studies include:
1) Ubiquitin proteasome system (UPS)-mediated protein degradation in excitability homeostasis
Our recent work identified two ubiquitin E3 ligases, murine double minute 2 (Mdm2) and neural precursor cell expressed developmentally downregulated gene 4-like (Nedd4-2), participating in activity-induced synapse elimination and excitability homeostasis. Our current research focuses on the identification of their substrates and downstream signaling pathways in the context of excitability regulation. We also employ multiple mouse models to understand how dysregulation of Mdm2 and Nedd4-2 may contribute to hyperexcitability in epilepsy and autism.
2) Translational control in neuronal and synaptic plasticity
My long-term effort has identified multiple mechanisms of translational control involved in various synaptic plasticity mechanisms. Particularly our recent work has discovered that Mdm2 and Nedd4-2 can both function as a translational suppressor and mediate translation-associated neural plasticity. Because abnormal translation is observed in multiple autism spectrum disorders, our research seeks to understand how dysregulated translation resulted from dysregulated Mdm2 or Nedd4-2 contributes to the deficits of synaptic or network plasticity in autism mouse models.
2020 James and Maxine Heath Excellence in Teaching Award
2019 Arnold O. Beckman Research Award
2016 - 2020 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
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 (in press) [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, Christian CA, Bacos JT, Lee KY, Zhu J, and Tsai NP (2016) Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling. Mol Brain 9:32
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.