Wei Lu photo

Wei Lu, Ph.D.

Senior Investigator
Address
Synapse and Neural Circuit Section

BG 35 RM 3C-1000
35 CONVENT DR
BETHESDA MD 20814

Dr. Lu received his Ph.D. degree from New York University (Ph.D., 2006). His graduate study, in the laboratory of Dr. Edward Ziff, was on biochemical characterization of neuronal glutamate receptors and their interacting proteins. He did his postdoctoral training in the laboratory of Dr. Roger Nicoll at the University of California, San Francisco, where he combined electrophysiological and single-cell genetic approaches to study excitatory synaptic transmission.

For details, please check the lab website: https://sites.google.com/site/lulaboratorynih/research

Synapses, the highly specialized cellular junctions, are essential for rapid chemical communication between neurons. These synaptic junctions physically and functionally connect individual neurons into continuous neural circuits that give rise to behavior and cognition. How are synaptic connections between neurons formed during development, how synapse specificity is established, what are the molecular and cellular mechanisms underlying the regulation of synaptic strength, and how does the regulation of synaptic strength influence animal behavior?

Currently, we are focusing on understanding the origin and regulation of neural inhibition mediated by GABAA receptors in the brain. These are under-studied areas that have many important questions, and answers to these questions will provide critical insights into both physiology and pathology of the brain. As such, questions directed at a deep and thorough understanding of GABAA receptors and GABAergic synapses are the major focus of our future research. In our lab, we mainly rely on rodent hippocampus as our model system to study these questions. Technically, we employ molecular, biochemical and genomic approaches to identify novel players in synaptic function, use molecular, genetic, optical and pharmacological approaches to manipulate synapses both in vitro and in vivo, and utilize electrophysiological, genetic and behavioral approaches to examine synaptic and neural circuit function. Ongoing projects in the lab include,

1. Molecular, cellular and systems mechanisms for the regulation of developmentfunction and plasticity of inhibitory synapses/circuits

2. New GABAA receptor auxiliary subunits and development of novel GABAA receptor psychopharmacology

3. Novel molecules, circuits and mechanisms involved in stressalcohol, general anesthesiasleep and consciousness

Wei Lu, Ph.D. PI

Qingjun Tian, Lab Manager

Wenyan Han, Ph.D., Research Fellow

Saurabh Pandey, Ph.D. Postdoc Fellow

Kunwei Wu, Ph.D. Postdoc Fellow

Guohao Wang, Ph.D. Postdoc Fellow

David Castellano, Ph.D. Graduate Student

Primary Publications at NINDS, NIH (2012-present)

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

Wu KW, Castellano D, Tian Q, Lu W (2021) Distinct regulation of tonic GABAergic inhibition by NMDA receptor subtypes. Cell Reports. Weblink

Wu KW, Han WY, Tian QJ, Li Y, Lu W (2021) Activity-and sleep-dependent regulation of tonic inhibition by Shisa7 Cell Reports. Weblink

Castellano D, Shepard RD, Lu W (2021) Looking for Novelty in an “Old” Receptor: Recent Advances Toward Our Understanding of GABAARs and Their Implications in Receptor Pharmacology. Frontiers in Neuroscience. Weblink (Review)

Wenyan Han, Ryan D. Shepard, Wei Lu (2020) Regulation of GABAARs by Transmembrane Accessory Proteins. Trends in Neurosciences. Weblink (Review)

Wenyan Han, Jun Li, Kenneth A. Pelkey, Saurabh Pandey, Xiumin Chen, Ya-Xian Wang, Kunwei Wu, Lihao Ge, Tianming Li, David Castellano, Chengyu Liu, Ling-gang Wu, Ronald S. Petralia, Joseph W. Lynch, Chris J. McBain, Wei Lu (2019) Shisa7 is a GABAA receptor auxiliary subunit controlling benzodiazepine actions. Science. Weblink

*Previewed by: Modulating anxiety and activity (2019) Science 11 Oct 2019. Weblink

*Discussed by Sciencedaily

Li J, Han WY, Wu KW, Li YP, Liu Q, Lu W (2019) A conserved tyrosine residue in the Slitrk3 carboxyl-terminus is critical for GABAergic synapse development. Front. Mol. Neurosci. Weblink

Jingjing Duan, Saurabh Pandey, Tianming Li, David Castellano, Xinglong Gu, Jun Li, Qingjun Tian and Wei Lu (2019) Genetic Deletion of GABAA Receptors Reveals Distinct Requirements of Neurotransmitter Receptors for GABAergic and Glutamatergic Synapse Development. Front. Cellular. Neurosci. Weblink

Gu XL and Wei Lu (2018) Genetic deletion of NMDA receptors suppresses GABAergic synaptic transmission in two distinct types of central neurons. Neuroscience Letters. Weblink

Wenyan Han, Huiqing Wang, Jun Li, Shizhong Zhang and Wei Lu (2017) Ferric Chelate Reductase 1 Like protein (FRRS1L) associates with dynein vesicles and regulates glutamatergic synaptic transmission. Front. Mol. Neurosci. Weblink

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. Weblink

*Previewed by: GABAergic Synaptogenesis: A Case for Cooperation (2017) Fritschy, Jean-Marc et al. Neuron. Weblink

*Recommended by F1000Prime

Hutchison MA, Gu X, Adrover MF, Lee MR, Hnasko TS, Alvarez VA and W Lu (2017) Genetic inhibition of neurotransmission reveals role of glutamatergic input to dopamine neurons in high-effort behavior. Molecular Psychiatry. Weblink

Lu W and Chen YL. (2017) Development of fast neurotransmitter synapses: General principle and recent progress. Brain Research Bulletin. Web link (Editorial)

Mao X, Gu X, Lu W. (2017) GSG1L regulates the strength of AMPA receptor-mediated synaptic transmission but not AMPA receptor kinetics in hippocampal dentate granule neurons. Journal of Neurophysiology. Web link

Lu W, Bromley-Coolidge S, Li J. (2016) Regulation of GABAergic synapse development by postsynaptic membrane proteins. Brain Research Bulletin. Web link (Review)

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. Web link or PDF

Gu X, Zhou L, Lu W. (2016) An NMDA receptor-dependent mechanism underlies inhibitory synapse development. Cell Reports. Web link or PDF

 

Collaborative Publications at NINDS, NIH (2012-present)

Marta Mota Vieira, Thien A. Nguyen, Kunwei Wu, John D. BadgerII, Brett M. Collins, Victor Anggono, Wei Lu, Katherine W. Roche (2020) An Epilepsy-Associated GRIN2A Rare Variant Disrupts CaMKIIα Phosphorylation of GluN2A and NMDA Receptor Trafficking. Cell Reports Volume 32, Issue 9, 1 September 2020. Weblink

Saurabh Pandey, Namrata Ramsakha, Rohan Sharma, Ravinder Gulia, Prachi Ojha, Wei Lu, Samarjit Bhattacharyya. (2020) The post-synaptic scaffolding protein Tamalin regulates ligand-mediated trafficking of metabotropic glutamate receptors. Journal of Biological Chemistry. Weblink

Thien A Nguyen , Kunwei Wu, Saurabh Pandey, Alexander W Lehr, Yan Li, Michael A Bemben, John D Badger 2nd, Julie L Lauzon, Tongguang Wang, Kareem A Zaghloul , Audrey Thurm, Mahim Jain, Wei Lu, Katherine W Roche. (2020) A Cluster of Autism-Associated Variants on X-Linked NLGN4X Functionally Resemble NLGN4Y. Neuron. Web link

Lin Luo, Mateusz C. Ambrozkiewizc, Fritz Benseler, Cui Chen, Emilie Dumontier, Susanne Falkner , Elisabetta Furlanis, Andrea M. Gomez, Naosuke Hoshina, Wei-Hsiang Huang , Mary Anne Hutchison, Yu Itoh-Maruoka, Laura A. Lavery, Wei Li, Tomohiko Maruo, Junko Motohashi, Emily Ling-Lin Pai, Kenneth A. Pelkey, Ariane Pereira,Thomas Phillips, Jennifer Sinclair, Jeff Stogsdill, Lisa Traunmüller, Jiexin Wang, Joke Wortel, Wenjia You, Nashat Abumaria, Kevin T. Beier, Harold Burgess, Constance L. Cepko, Jean-François Cloutier, Cagla Eroglu, Sandra Goebbels, Pascal S. Kaeser, Jeremy N. Kay, Wei Lu, Liqun Luo, Kenji Mandai, Chris J. McBain, Klaus-Armin Nave, Marco A.M. Prado, Vania F. Prado, Jeffrey Rothstein, John L. R. Rubenstein, Gesine Saher, Kenji Sakimura, Joshua R. Sanes, Peter Scheiffele, Yoshimi Takai, Hisashi Umemori, Matthijs Verhage, Michisuke Yuzaki, Huda Yahya Zoghbi, Hiroshi Kawabe, Ann Marie Craig. (2020) Optimizing Nervous System-Specific Gene Targeting with Cre Driver Lines: Prevalence of Germline Recombination and Influencing Factors. Neuron. Weblink

Jaehoon Jeong, Saurabh Pandey, Yan Li, John D. Badger II, Wei Lu, and Katherine W. Roche (2019) PSD-95 binding dynamically regulates NLGN1 trafficking and function. PNAS. Weblink

Tonghui Su, Yi Lu, Yang Geng, Wei Lu, Yelin Chen (2019) How could N-Methyl-D-Aspartate Receptor Antagonists Lead to Excitation Instead of Inhibition? Brain Science Advances. Weblink

Chia-Yu Yeh, Brent Asrican, Jonathan Moss, Luis Jhoan Quintanilla, Ting He, Xia Mao, Frederic Cassé, Elias Gebara, Hechen Bao, Wei Lu, Nicolas Toni, Juan Song (2018) Mossy Cells Control Adult Neural Stem Cell Quiescence and Maintenance through a Dynamic Balance between Direct and Indirect Pathways. Neuron. Weblink

Thomas Steinkellner, Vivien Zell, Zachary J. Farino, Mark S. Sonders, Michael Villeneuve, Robin J. Freyberg, Serge Przedborski, Wei Lu, Zachary Freyberg, and Thomas S. Hnasko (2018) Role for VGLUT2 in selective vulnerability of midbrain dopamine neurons. Journal of Clinical Investigation. Weblink

Shuxi Liu, Liang Zhou, Hongjie Yuan, Marta Vieira, Antonio Sanz-Clemente, John D. Badger, Wei Lu, Stephen F. Traynelis andKatherine W. Roche. (2017) A rare variant identified within the GluN2B C-terminus in a patient with autism affects NMDA receptor surface expression and spine density. Journal of Neuroscience, 0827-16. Weblink

RM Lomash, X Gu, RJ Youle, W Lu, KW Roche. (2015) Neurolastin, a Dynamin Family GTPase, Regulates Excitatory Synapses and Spine Density. Cell reports 12 (5), 743-751. Web link

MP Lussier, X Gu, W Lu, KW Roche. (2014) Casein kinase 2 phosphorylates GluA1 and regulates its surface expression. European Journal of Neuroscience 39 (7), 1148-1158. Web link