DEPARTMENT OF NEUROBIOLOGY

Specializations

Regions(s): Systems Neuroscience; Cellular and Molecular Neuroscience; Developmental Neuroscience; Neurogenetics; Brain and Behavior

Research interest(s): Developmental and Activity-Dependent Remodeling of Chromatin Architecture; Epigenetic Regulation of Neural Circuits; Cerebellar Circuits in Motor Learning

Research Summary

Large numbers of genes turn on and off in temporally and spatially precise patterns in the brain to regulate neural circuit development and refinement. The Yang laboratory is interested in the chromatin mechanisms operating in the nucleus that organize functional neural circuits. We are studying how developmental signals or sensory experience in vivo activate these chromatin mechanisms to orchestrate programs of gene expression in the brain. Our model system is the mouse cerebellum, a hindbrain structure important for motor coordination and motor learning. A major goal is to elucidate how chromatin mechanisms and gene expression networks pattern the neural circuits underlying motor behavior and learning and memory.

The laboratory deploys next-generation molecular neuroscience approaches including epigenetics and chromatin conformation profiling using massive parallel sequencing, single-cell sequencing, and bioinformatics, as well as systems neuroscience tools including optogenetics, in vivo two-photon calcium imaging, and mouse behavior.

Selected Publications

• Yamada T*, Yang Y*, Valnegri P*, Juric I, Abnousi A, Markwalter KH, Guthrie AN, Godec A, Oldenborg A, Hu M, Holy TE, Bonni A. Sensory experience remodels genome architecture in neural circuit to drive motor learning. Nature. 2019 May 30;569(7758):708-13.
• Yang Y*, Yamada T*, Hill KK, Hemberg M, Reddy NC, Cho HY, Guthrie AN, Oldenborg A, Heiney SA, Ohmae S, Medina JF, Holy TE, Bonni A. Chromatin Remodeling Inactivates Activity Genes and Regulates Neural Coding. Science. 2016 Jul 15;353(6296):300-5.
• Yamada T*, Yang Y*, Hemberg M, Yoshida T, Cho HY, Murphy JP, Fioravante D, Regehr WG, Gygi SP, Georgopoulos K, Bonni A. Promoter Decommissioning by the NuRD Chromatin Remodeling Complex Triggers Synaptic Connectivity in the Mammalian Brain. Neuron. 2014 Jul 2;83(1):122-34.
• Yang Y, Kim AH, Yamada T, Wu B, Bilimoria PM, Ikeuchi Y, de la Iglesia N, Shen J, Bonni A. A Cdc20-APC ubiquitin signaling pathway regulates presynaptic differentiation. Science. 2009 Oct 23;326(5952):575-8.

Selected Honors/Awards

• 2011-2013       Ruth L. Kirschstein NRSA Postdoctoral Training Grant
• 2008-2010       Edward R. and Anne G. Lefler Fellowship, Harvard Medical School
• 2008                Albert J. Ryan Fellowship
• 2005-2008       National Science Foundation Graduate Research Fellowship           
• 2004-2005       Ruth L. Kirschstein NRSA Predoctoral Training Grant        
• 2004                Deans’ Award for Academic Accomplishment, Stanford University
• 2001-2004       Robert C. Byrd Scholarship
• 2001-2002       National Merit Scholarship