The Yi laboratory is broadly interested in the molecular pathways that shape nervous system development and function, with the ultimate goal of understanding how dysfunction in these pathways contributes to disease. The current focus of the lab is on autism spectrum disorders (ASD). We use genetic information from human patients to guide our in vitro and in vivo experiments using biochemical, genetic manipulation, cell biological, and microscopy techniques. These studies aim to bridge our knowledge of disease genetics with a mechanistic understanding of the neurobiology of ASD.
The lab is studying the role of the ubiquitin ligase UBE3A in the brain. Individuals lacking UBE3A activity in the brain develop a severe form of mental retardation known as Angelman syndrome, while excessive UBE3A activity, through duplication of the UBE3A gene, causes a highly penetrant form of autism. It was recently discovered in the lab that a single phosphorylation event in UBE3A turns off its ubiquitin ligase activity. This phosphorylation site is mutated in autism, thereby mimicking excessive UBE3A activity seen in individuals with multiple copies of UBE3A. The lab is using the insights from this study to identify the pathways involved in ASD pathogenesis, and to define the developmental timepoint for ASD onset.
- Yi, JJ, Paranjape, SR, Walker, MP, Choudhury, R, Wolter, JM, Fragola, G, Emanuele, MJ, Major, MB, Zylka, MJ. The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/β-catenin pathway by inhibiting the proteasome. Journal of Biological Chemistry. 2017; 292(30):12503-12515. doi: 10.1074/jbc.M117.788448. Epub 2017 May 30.
- Yi JJ, Berrios J, Newbern JM, Snider WD, Philpot BD, Hahn KM, Zylka MJ. An autism-linked mutation disables phosphorylation control of UBE3A. Cell. Aug 13, 2015; 162(4):795-807. doi: 10.1016/j.cell.2015.06.045.
- Yi JJ, Barnes AP, Hand R, Polleux F, Ehlers MD. TGF-beta signaling specifies axons during brain development. Cell. Jul 9, 2010; 142(1):144-57. doi: 10.1016/j.cell.2010.06.010.
- Yi JJ, Wang H, Vilela M, Danuser G, Hahn KM. Manipulation of endogenous kinase activity in living cells using photoswitchable inhibitory peptides. ACS Synthetic Biology. Nov 21, 2014; 3(11):788-95. doi: 10.1021/sb5001356.
- Karginov AV, Tsygankov D, Berginski M, Chu PH, Trudeau ED, Yi JJ, Gomez S, Elston TC, Hahn KM. Dissecting motility signaling through activation of specific Src-effector complexes. Nature Chemical Biology. Apr 2014; 10(4):286-90. doi: 10.1038/nchembio.1477.
- Arenkiel BR, Hasegawa H, Yi JJ, Larsen RS, Wallace ML, Philpot BD, Wang F, Ehlers MD. Activity-induced remodeling of olfactory bulb microcircuits revealed by monosynaptic tracing. PLoS One. 2011; 6(12):e29423. doi: 10.1371/journal.pone.0029423.
See a complete list of Dr. Yi’s publications on PubMed.
2001 BS, Biochemistry and Molecular Biology, Dickinson College, Carlisle, PA
2009 PhD, Pharmacology
Duke University, Durham, NC
2006, Ruth K. Broad Biomedical Research Foundation Predoctoral Fellowship
2011, F32 Kirschstein National Research Service Award
2011-2014, Christina Castellana Postdoctoral Fellowship, The Foundation for Angelman Syndrome Therapeutics
2015, The University of North Carolina Postdoctoral Award for Research Excellence
2017, Bridge to Independence Award, The Simons Foundation
2018, NARSAD Young Investigator Award, Brain and Behavior Research Foundation
2018, Whitehall Foundation Research Grant
2019, Alfred P. Sloan Foundation Research Fellowship