We are using GABAergic synapses in rodents as the model system to understand brain function and disorder, with three considerations in mind: 1) biology and physiology of GABAergic synapses are complex but greatly understudied; 2) GABAergic synapses are important in almost every aspects of brain physiology and dysregulation of GABAergic synapses has been implicated in pathogenesis of numerous brain disorders; 3) GABA_A receptors are prolific targets for a number of clinical, therapeutic or recreational drugs that are widely used to treat anxiety, depression, sleep disorder, pain and epilepsy or to induce general anesthesia.

Ongoing projects in the lab include, 1) Identification and characterization of novel molecules and signaling pathways critical for GABAergic synapse development/transmission and their roles in animal behavior and brain disorder; 2) Discovering novel GABA_A receptor auxiliary subunits and development of new GABA_A receptor psychopharmacology; 3) Studying molecular and neural circuit mechanisms underlying general anesthesia and consciousness. These projects will help understand biology and pathology of GABAergic synapses and their functions in the brain, provide new potential drug targets, and bring new hope for the treatment of diseases such as anxiety and depression, sleep disorders, epilepsy and alcoholism.

Dr. Lu’s lab has identified novel transmembrane proteins that bind to GABA_A receptors and regulate receptor biophysical and pharmacological properties (Han et al., Science 2019; Wu et al., Cell Reports 2021 and Neuropsychopharmacology 2022; Castellano et al., Journal of Neuroscience 2022; Wang et al., Cell 2024), has discovered key molecules and pathways for GABAergic synaptogenesis and plasticity (Gu et al., Cell Reports 2016; Li et al., Neuron 2017;Wu et al., Cell Reports 2021; Wu et al., PLOS Biology 2022), and has revealed novel signal pathways at GABAergic synapses that are highly sensitive to chronic stress and that can be used to reverse anxiety-like behaviors in rodents (Pandey et al., PNAS 2024 and Journal of Neuroscience 2025). 

Director’s Award, NINDS, NIH, 2019

K99 Award, NIMH, NIH, 2011

American Heart Association Postdoctoral Fellowship, 2008-2010

Grass Foundation Award for Summer Research, 2005

1.Pandey S, Ostergren S, Li J, Peng SX, Tian QJ, Dong LJ, Lu W (2025) A critical role of Neuroligin 2 C-terminus in OCD and social behavior. Journal of Neuroscience. 1417-24

2.Wang GH, Peng SX, Castellano D, Wu KW, Han WY, Tian QJ, Dong LJ, Li Y, Lu W (2024) The TMEM132B-GABA_A receptor complex controls alcohol actions in the brain. Cell. 187, 1-20

3.Pandey S, Han WY, Li J, Shepard RD, Wu KW, Castellano D, Tian QJ, Dong LJ, Li Y, Lu W (2024) Reversing anxiety by targeting a stress-responsive signaling pathway. PNAS. 121 (31)

4.Castellano D, Wu KW, Keramidas A, Lu W (2022) Shisa7-dependent regulation of GABA_A receptor single-channel gating kinetics. Journal of Neuroscience. 42 (47) 8758-8766.

5.Wu KW, Han WY, Lu W (2022) Sleep and wake cycles dynamically modulate hippocampal inhibitory synaptic plasticity. PLOS Biology. 20(11), e3001812

6.Wu KW, Shepard RD, Castellano D, Tian Q, Dong LJ, Lu W (2022) Shisa7 phosphorylation regulates GABAergic transmission and neurodevelopmental behaviors. Neuropsychopharmacology 47:2160-2170

7.Wu KW, Castellano D, Tian QJ, Lu W (2021) Distinct regulation of tonic GABAergic inhibition by NMDA receptor subtypes. Cell reports 37 (6), 109960

8.Wu KW, Han WY, Tian QJ, Li Y, Lu W (2021) Activity-and sleep-dependent regulation of tonic inhibition by Shisa7. Cell reports 34 (12), 108899

9.Han WY, Shepard RD, Lu W (2021) Regulation of GABA_ARs by transmembrane accessory proteins. Trends in Neurosciences 44 (2), 152-165 (Review)

10.Han WY, Li J, Pelkey KA, Pandey S, Chen XM, Wang YX, Wu KW, Ge LH, Li TM, Castellano D, Liu CY, Wu LG, Petralia RS, Lynch JW, McBain CJ, Lu W (2019) Shisa7 is a GABA_A receptor auxiliary subunit controlling benzodiazepine actions. Science. 366, 246-250

11. Hutchison MA, Gu X, Adrover MF, Lee MR, Hnasko TS, Alvarez VA and Lu W (2018) Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior. Molecular Psychiatry. 23, 1213-1225

12. Li J, Han WY, Pelkey KA, Duan JJ, Mao X, Wang YX, Craig MT, Dong LJ, Petralia RS, McBain CJ, Lu W (2017) Molecular Dissection of Neuroligin 2 and Slitrk3 Reveals an Essential Framework for GABAergic Synapse Development. Neuron. 96(4):808-826

13. Gu X, Mao X, Lussier MP, Hutchison MA, Zhou L, Hamra FK, Roche KW, Lu W. (2016) GSG1L suppresses AMPA receptor-mediated synaptic transmission and uniquely modulates AMPA receptor kinetics in hippocampal neurons. Nature Communications. 7:10873

14. Gu X, Zhou L, Lu W. (2016) An NMDA receptor-dependent mechanism underlies inhibitory synapse development. Cell Reports, 14, 1–8.

15. Lu W, Bushong EA, Shih TP, Ellisman MH, Nicoll RA (2013) The cell-autonomous role of excitatory synaptic transmission in the regulation of neuronal structure and function. Neuron. May 8;78(3):433-9.

16.Lu W, Isozaki K, Roche KW, Nicoll RA. (2010) Synaptic targeting of AMPA receptors is regulated by a CaMKII site in the first intracellular loop of GluA1. PNAS. Dec 21;107(51): 22266-71

17.Lu W, Shi Y, Jackson AC, Bjorgan K, During MJ, Sprengel R, Seeburg PH, Nicoll RA. (2009) Subunit composition of synaptic AMPA receptors revealed by a single-cell genetic approach. Neuron 62, 254-268.

18.Lu Wand Ziff EB. (2005). PICK1 interacts with ABP/GRIP to regulate AMPA receptor trafficking. Neuron 47, 407-421.

We have multiple openings available for postdoctoral fellows and graduate students.