423A Burrill Hall
Office: (217) 244-5620
Lab: (217) 244-7095
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
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 neural plasticity in health and disease
A hyperexcitable brain circuit is a common neurological abnormality observed in patients with various psychiatric and neurodevelopmental disorders, including schizophrenia and bipolar, mood disorders, and autism spectrum disorders. Identifying and understanding the mechanisms that regulate neuronal excitability will likely 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 neuronal excitability at synaptic, network and system levels. Two particular areas in which my laboratory studies include:
1) Ubiquitin proteasome system (UPS)-mediated protein degradation in homeostatic neural plasticity
Our recent work identified an ubiquitin E3 ligase, Murine double minute 2 (Mdm2) plays a major role in regulating activity-induced synapse elimination. Our current research focuses on the regulation of Mdm2 and its substrate p53 upon neuronal activity stimulation. We aim to understand how Mdm2-p53 signaling contributes to the homeostatic control of neuronal excitability and synaptic plasticity. We also investigate whether and how Mdm2-p53 signaling is disrupted in the mouse model of fragile x syndrome (FXS), the Fmr1 KO.
2) Translational control in homeostatic neural plasticity
In neurons, the messenger RNA (mRNA) can be localized to distal compartments (axons or dendrites) and translated into proteins locally. This local translation is thought to provide efficient and spatial regulations for selected genes in response to stimulations. My long-term effort has identified multiple locally translated proteins and signaling pathways involved in various synaptic plasticity mechanisms. Because an abnormal gene translation is observed in several neurodevelopmental disorders including FXS, my research aims to understand how the dysregulated protein translation, particularly near dendrites/synapses, contributes to the deficits of homeostatic synaptic and network plasticity in neurodevelopmental disorders.
2015 NARSAD Young Investigator Award
2014 Simons Foundation Autism Initiative-Explorer Award
2011 National Research Service Award (NRSA) from NICHD/NIH
2011 Meritorious Award at Postdoctoral Symposium at UTSW
2010 Dr. Marvin and Hadassah Bacaner Research Award in Pharmacology, University of Minnesota
2008 Veneziale-Steer Research Award, University of Minnesota
2008 Milne Brandenberg Award for outstanding graduate research, University of Minnesota
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]
Tsai NP*, Guo W, Wilkerson JR and Huber KM* (2017) FMRP-Dependent Mdm2 Dephosphorylation is required for MEF2-Induced Synapse Elimination. Hum Mol Genet. 26:293-304 (*co-corresponding authors)
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
Tsai NP (2014). Ubiquitin Proteasome System-Mediated Degradation of Synaptic Proteins: An Update from the Postsynaptic Side. Biochimica et Biophysica Acta 1843:2838-2842
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.
Tsai NP, Bi J, Loh HH, Wei LN (2006) Netrin-1 signaling regulates de novo protein synthesis of kappa opioid receptor by facilitating polysomal partition of its mRNA. J Neurosci 26: 9743-9749.