Investigator, McGovern Institute
James W. (1963) and Patricia T. Poitras Professor, Brain and Cognitive Sciences; Director, Model Systems and Neurobiology, Stanley Center for Psychiatric Research; Institute Member, Broad Institute of MIT and Harvard
Guoping Feng studies the function of synapses and their disruption in animal models of neurodevelopmental and psychiatric disease.
Guoping Feng studies the development and function of synapses – the interconnections between neurons – and their disruption in brain disorders. He uses molecular genetics combined with behavioral and electrophysiological methods to study the molecular components of the synapse and to understand how disruptions in these components can lead to neurodevelopmental and psychiatric disease. By understanding the molecular, cellular, and circuit changes underlying brain disorders, the Feng lab hopes one day to help develop new and effective treatments for brain disorders.
Synaptic communication requires neurotransmitters to bind to receptors that are tightly localized to the postsynaptic site. These receptors are anchored in place through a complex of proteins known as the postsynaptic density (PSD). Much more than a passive scaffold, the PSD is a site for neural plasticity that is modulated by experience and learning. Disruption of the PSD is expected to have wide-ranging effects on behavior, a hypothesis that Feng is exploring in his research.
Feng has previously shown that mutations in one key component of the PSD, known as Sapap3, causes repetitive grooming behavior in mice that resembles human obsessive-compulsive disorder (OCD). Sapap3 is specifically expressed in the striatum, a brain region that has been implicated in OCD and many other disorders including autism, Parkinson’s and Huntington’s disease. Feng has shown that altered synaptic communication between the cortex and the striatum may account for the repetitive behaviors of the mutant mice.
Feng is also studying another synaptic scaffold protein, known as Shank3. Mutations in the Shank3 gene in humans lead to Phelan-McDermid syndrome, characterized by hypotonia, global developmental delay, intellectual disability and autism spectrum disorders (ASD). He has found that mutations in the Shank3 gene lead to repetitive behaviors, sensory hyper-sensitivity, and abnormalities of social interaction in mice that are relevant to autism. Using genetic tools for labeling and manipulating specific cell types in the living brain, Feng is working to dissect the circuit level deficits underlying these abnormal behaviors. He is also creating new and more realistic animal models of human psychiatric disorders that can be used to discover new therapies for these conditions.
In the course of his work, Feng has developed many genetic tools for probing the function of synapses and circuits in the living brain. These include mice expressing green fluorescent protein in single neurons for long-term imaging; mice expressing light-sensitive ion channels that allow optical manipulation of neural activity; and mice expressing genetically encoded activity sensors to monitor neural activity in vivo.
Guoping Feng joined the McGovern Institute in 2010. He is a faculty member in MIT’s Department of Brain and Cognitive Sciences, where he holds the Poitras Professorship of Neuroscience. Feng is the Director of Model Systems and Neurobiology in the Stanley Center for Psychiatric Research. Originally from Zhejiang Province in China, he received his PhD from SUNY Buffalo. Before moving to MIT, he was a faculty member at Duke University.
Du, J, Simmons, S, Brunklaus, A, Adiconis, X, Hession, CC, Fu, Z et al.. Differential excitatory vs inhibitory SCN expression at single cell level regulates brain sodium channel function in neurodevelopmental disorders. Eur. J. Paediatr. Neurol. 2019; :. doi: 10.1016/j.ejpn.2019.12.019. PubMed PMID:31928904 .
Nakajima, M, Schmitt, LI, Feng, G, Halassa, MM. Combinatorial Targeting of Distributed Forebrain Networks Reverses Noise Hypersensitivity in a Model of Autism Spectrum Disorder. Neuron. 2019;104 (3):488-500.e11. doi: 10.1016/j.neuron.2019.09.040. PubMed PMID:31648899 .
Sanders, SJ, Sahin, M, Hostyk, J, Thurm, A, Jacquemont, S, Avillach, P et al.. A framework for the investigation of rare genetic disorders in neuropsychiatry. Nat. Med. 2019;25 (10):1477-1487. doi: 10.1038/s41591-019-0581-5. PubMed PMID:31548702 .