Research Abstract

Our 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.

We are 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. We recently discovered 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. We are using the insights from this study to identify the pathways involved in ASD pathogenesis, and to define the developmental timepoint for ASD onset.

Selected Publications

  • Yi JJ, Berrios J, Newbern JM, Snider WD, Philpot BD, Hahn KM, Zylka MJ. A Phosphorylation Switch Controls UBE3A Ubiquitin Ligase Activity and Dendritic Spine Development. Cell. 2015 Aug 13; 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. 2010 Jul 9; 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. 2014 Nov 21; 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. 2014 Apr; 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

For a complete list of Dr. Yi's publications, click here.

Jason Yi, PhD

Assistant Professor of Neuroscience

Washington University
School of Medicine
Campus Box 8108
McDonnell Medical Sciences, 808
St. Louis, MO 63110
(314) 273-1664

Other Information

2001 BS, Biochemistry and Molecular Biology, Dickinson College, Carlisle, PA

2009 PhD, Pharmacology
Duke University, Durham, NC

Selected Honors
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

2017, Bridge to Independence Award, The Simons Foundation