He won the International Distinguished Dissertation Award (top Ph.D. thesis in science in U.S.A. and Canada, awarded once every 5 years) for seminal work with HHMI Investigator Michael Welsh by uncovering the ion channel and regulatory functions of the cystic fibrosis gene product (Cell, Science, Nature, and PNAS). his postdoctoral fellowship at Massachusetts Institute of Technology with Nobel Laureate Susumu Tonegawa led to training in Cre-LoxP conditional mouse molecular genetics, brain slice electrophysiology and synaptic physiology, in vivo electrophysiological approaches, and behavioral neurosciences. At Harvard, his laboratory leverages these technologies to investigate the circuit and molecular basis of genetic forms of human neurological and psychiatric disease including epilepsy and autism. His laboratory identified the first human genetic epilepsy disorder with defective postnatal developmental pruning and maturation of glutamatergic circuits (Zhou et al. Nature Medicine 2009). They created the first genetic mouse model of a frequent and strongly penetrant genetic autism spectrum disorder (maternal 15q11-13 triplications; Smith et al. Science TM 2011). increased Ube3a gene dosage alone reconstituted the behavioral deficits of autism (impaired social interaction and vocalization and repetitive behavior). Recently (Krishnan et al. Nature 2017), they applied transcriptional profiling, protein interaction network analysis, Cre-loxP conditional genetics, stereotaxic viral vectors, chemogenetics, and optogenetics to map the sociability deficits resulting from increased UBE3A. Cbln1 encodes a secreted synapse organizing protein that bridges presynaptic neurexin (Nrxn1) and postsynaptic glutamate delta receptor (Grid1), two genes deleted in autism. They discovered that UBE3A and seizures synergize to repress Cbln1 gene expression. Loss of Cbln1 disrupts synapses of previously enigmatic glutamatergic neuron in the mesolimbic motivation circuits of the ventral tegmental area (VTA) to impair social behavior.