RESEARCH PROGRAMS AND AFFILIATIONS
The Yao Lab studies neural mechanisms underlying reward, affect, and prosocial behaviors in normal and disease conditions, with a focus in dopamine and the prefrontal cortex (PFC). Combining electrophysiology, behavior, optogenetics, and chemogenetics, we investigate how intrinsic and synaptic plasticity and modulation in PFC circuits are impaired in addiction, FTD (frontotemporal dementia), and related brain disorders, leading to behavioral deficits associated with these diseases. Employing molecular and cellular approaches, we also elucidate novel molecular mechanisms that regulate synapse formation, stabilization, and pruning. We use transgenic and viral-transduced mouse models and human iPSC-derived neurons.
Wei-Dong Yao, PhD CV
Dr. Yao is a SUNY Empire Scholar and Director of the Molecular Cellular Neuropsychiatry Laboratory at SUNY Upstate. The mission of the Lab is to understand how psychiatric diseases damage brain cells and their proper wiring, and how these impairments cause mental illnesses. The hypothesis is that impaired assembly, function, and plasticity of synapses (small junctions that permit nerve cells to pass an electrical or chemical signal from one to another) and neural circuits underlie cognitive, memory, and emotional deficits of essentially all neuropsychiatric diseases. He is investigating this hypothesis using a number of state-of-the-art molecular, cellular, and electrophysiological technologies on genetically engineered mouse models and induced pluripotent stem cells (iPS cells) derived from human patients. His major interests are addiction, schizophrenia, autism, and primarily prefrontal cortex related brain and mental diseases. His previous work done at Harvard Medical School has identified new brain signaling pathways that regulate synapse formation and stabilization and neural circuit rewiring that provide fundamental breakthroughs about the pathogenesis of these diseases. At SUNY Upstate he will continue the cutting-edge research, and the knowledge obtained will help develop more effective treatment strategies for these diseases.
Choi SY, Lopez-Gonzalez R, Krishnan G, Phillips HL, Li AN, Seeley WW, Yao WD, Almeida S, Gao FB. (2019) C9ORF72-ALS/FTD-associated poly(GR) binds Atp5a1 and compromises mitochondrial function in vivo. Nat Neurosci. 22(6):851-862. doi: 10.1038/s41593-019-0397-0. Epub 2019 May 13.
Ma Q, Ruan H, Peng L, Zhang M, Gack MU, Yao WD. (2017) Proteasome-independent polyubiquitin linkage regulates synapse scaffolding, efficacy, and plasticity. Proc Natl Acad Sci U S A;2017 Sep 25. pii: 201620153. doi: 10.1073/pnas.1620153114. F1000Prime Recommended. https://f1000.com/prime/731737130?bd=1
Vallender EJ, Goswami DB, Shinday NM, Westmoreland SV, Yao WD*, Rowlett JK*. (2017) Transcriptomic Profiling of the Ventral Tegmental Area and Nucleus Accumbens in Rhesus Macaques Following Long-Term Cocaine Self-Administration. Drug Alcohol Dependence 175:9-23. 2017.01.030. (*Co-senior authors).
Ruan H, Yao WD. (2016) Cocaine Promotes Coincidence Detection and Lowers Induction Threshold during Hebbian Associative Synaptic Potentiation in Prefrontal Cortex. J Neurosci 2016 Dec 16. pii: 2257-16.
Saur T, Cohen BM, Ma Q, Babb SM, Buttner EA, Yao WD. (2016) Acute and Chronic Effects of Clozapine on Cholinergic Transmission in Cultured Mouse Superior Cervical Ganglion Neurons. J Neurogenet 30:297-305.
Hou Q, Ruan H, Gilbert J, Wang G, Ma Q, Yao WD, Man HY. (2015) MicroRNA miR124 is required for the expression of homeostatic synaptic plasticity. Nat Commun 2015 Dec 1;6:10045. doi: 10.1038/ncomms10045.
Jakovcevski M, Ruan H, Shen EY, Dincer A, Javidfar B, Ma Q, Peter CJ, Cheung I, Mitchell AC, Jiang Y, Pothula V, Stewart F, Ernst P, Yao WD*, Akbarian S*. (2015) Neuronal kmt2a/mll1 histone methyltransferase is essential for prefrontal synaptic plasticity and working memory. J Neurosci 35:5097-108. (*Co-corresponding authors).
Gascon E, Lynch K, Ruan H, Verheyden J, Sun D, Jiao J, Jakovcevksi M, Tapper, AR, Akbarian S, Yao WD, Gao FB. (2014) Alterations in microRNA-124 and AMPA receptors contribute to social behavioral deficits in frontotemporal dementia. Nat Med 20:1444-51.
Peng L, Liu H, Ruan H, Tepp WH, Stoothoff WH, Brown RH, Johnson EA, Yao WD, Zhang SC, and Dong M. (2013) Cytotoxicity of Botulinum Neurotoxins Reveals Essential Neuronal Plasma Membrane SNAREs. Nat Commun 4:1472.
Xu TX, Yao WD. (2010) D1 and D2 dopamine receptors in separate circuits cooperate to drive associative long-term potentiation in the prefrontal cortex. Proc Natl Acad Sci U S A; 107:16366-71.
Xu TX, Sotnikova TD, Liang C, Zhang J, Jung JU, Spealman RD, Gainetdinov RR, Yao WD. (2009) Hyperdopaminergic tone erodes prefrontal LTP via a D2 receptor-operated protein phosphatase gate. J Neurosci 29:14086-99.
Zhang JP, Xu TX, Hallett PJ, Watanabe M, Grant SGN, Isacson O Yao WD (2009). PSD-95 Uncouples Dopamine-Glutamate Interaction in the D1/PSD-95/NMDA Receptor Complex. J Neurosci 29: 2948-2960.
Yao WD, Gainetdinov RR, Arbuckle MI, Sotnikova TD, Beaulieu JM, Cyr M, Torres GE, Grant SGN, Caron MG (2004). Identification of PSD-95 as a Regulator of Dopamine-Mediated Synaptic and Behavioral Plasticity. Neuron 41:625-638.
Torres GE#, Yao WD#, Mohn AR, Quan H, Caron MG (2001). Functional Interaction between Monoamine Plasma Membrane Transporters and the PDZ Domain-Containing Protein PICK1. Neuron 30: 121-134. (#Co-first authors).
Yao WD, Rusch J, Poo MM, Wu CF (2000). Spontaneous Acetylcholine Secretion from Developing Growth Cones of Drosophila Central Neurons in Culture: Effects of cAMP-Pathway Mutations. J Neurosci 20: 2626-37.
Harvard Med School: Protein's Balancing Act May Provide Handle on Psychiatric Disease