Professor Wei Lu earned his PhD from New York University. After that, he conducted postdoctoral research at the University of California, San Francisco, and later served as a Senior Principal Investigator at the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke (NINDS) before returning to China. 

Professor Wei Lu has long focused on synaptic development and functional regulation, as well as the neurobiological mechanisms underlying anxiety, depression, anesthesia, and alcohol effects. 

Professor Wei Lu has proposed several novel prospectives on synaptic development and functional regulation, identified multiple previously unknown proteins that regulate synaptic function, and systematically revealed synaptic function and related pathological mechanisms. His work holds promise for developing new therapeutic strategies for insomnia, anxiety, depression, alcoholism, and for improving anesthetic practice. Moving forward, he aims to develop next-generation therapeutics targeting GABA_A receptors for brain disorders. 

Major Awards and Honors

2019 Director's Award, National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health (NIH) 

2011 Principal Investigator Development Award, National Institute of Mental Health (NIMH), National Institutes of Health (NIH)

Lab Research Directions

Professor Wei Lu's lab employs rodent GABAergic synapses as a primary model system to investigate the molecular and circuit mechanisms in brain physiology and pathology. Main research projects include: 

1. Molecular mechanisms governing the development and transmission of GABAergic synapses, and their roles in behavior and neurological disorders;

2. Novel auxiliary subunits of the GABA_A receptor and related psychopharmacology; 

3. Molecular and circuit mechanisms of anesthesia and consciousness. 

These studies deepen our understanding of GABAergic synaptic function and regulation in the brain, identify new potential drug targets, and offer novel therapeutic approaches for brain disorders such as epilepsy, anxiety, insomnia, and alcohol addiction.

Selected Publications

1. 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, 6649–6668

This study identifies TMEM132B, a single-pass transmembrane protein that binds GABA_A receptors and amplifies alcohol's positive allosteric action, as a key regulator of alcohol-induced behaviors. This study demonstrates the critical role of TMEM132B in reducing alcohol consumption while concurrently enhancing alcohol's anxiety reducing, sedative, and sleep-promoting properties.

2. 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, 246-2

This study identifies Shisa7 as the first auxiliary subunit that modulates both the kinetics and pharmacology of GABA_A receptors, and elucidates the molecular mechanisms underlying the anxiety reducing, sedative, and hypnotic actions of benzodiazepines.

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)

This study identifies a stress-sensitive inhibitory synaptic pathway whose pharmacological manipulation reverses anxiety and depression symptoms in chronically stressed mice, offering novel therapeutic targets for these conditions.

4. 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

This study systematically reveals the molecular framework underlying GABAergic synapse development and proposes a novel therapeutic strategy for epilepsy.

5. 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

This study reveals how tonic inhibition in the brain is regulated by GABA_A receptor auxiliary subunits and explores the role of sleep and circadian rhythms in this modulatory process.

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

This study reveals how distinct NMDA receptor subtypes in the brain differentially regulate tonic inhibition and illustrates how these regulatory mechanisms are altered in epilepsy.

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

This study reveals that NMDA receptors play a crucial role in the development of GABAergic synapses. This finding suggests a novel mechanism for regulating neuronal excitation/inhibition balance and provides a new insight for understanding the molecular mechanisms underlying neurodevelopmental disorders such as autism.

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

This study reveals the plasticity of GABAergic synapses, which is modulated by sleep and circadian rhythms. This finding illustrates how fine-tuning brain activities occur at the synaptic level under physiological conditions.

9. 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.

This study provides a precise quantification of the subtypes and composition of synaptic AMPA receptors, laying the foundation for understanding the molecular mechanisms underlying AMPA receptor transportation and synaptic plasticity.

10. 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.

This study addresses a long-standing problem in the field by generating a novel mouse model lacking both AMPA and NMDA receptors via multiplexed gene knockout, thereby elucidating the functions of these receptors in excitatory synapse development. 

Professor Wei Lu has published over 50 papers as the first or corresponding author in leading journals, including Science, Cell, Neuron, PNAS, Nature Communications, Molecular Psychiatry, and Cell Reports. 

He has proposed several novel prospectives on synaptic development and functional regulation, identified multiple previously unknown proteins that regulate synaptic function, and systematically revealed synaptic function and related pathological mechanisms, thereby laying a solid foundation for understanding the molecular mechanisms underlying learning, memory, and synaptic plasticity. 

His work has identified several novel molecular targets for treating anxiety, depression, epilepsy, alcoholism, and for improving anesthetic practice, offering novel strategies for developing next-generation agents for brain disorders and clinical anesthesia.