Andrew Yoo, Ph.D.

Assistant Professor
Developmental Biology

Developmental, Regenerative and Stem Cell Biology Program
Neurosciences Program

  • 314-362-1811

  • 314-362-1814

  • 8103

  • yooa@WUSTL.EDU

  • http://yoolab.wustl.edu

  • neurogenesis, microRNA, cell fate reprogramming, chromatin remodeling, regenerative medicine

  • Dissecting genetic pathways underlying microRNA-mediated neurogenesis and neuronal reprogramming to generate human neurons

Research Abstract:

The general goal of our research is to understand genetic and molecular mechanisms underlying specification of cell fates. We are particularly interested in the process of neurogenesis mediated by small non-coding RNA molecules, microRNAs that control the activity of chromatin remodeling complexes during neural development. In addition, we recently discovered that two brain-enriched microRNAs, miR-9/9* and miR-124, are neurogenic molecules that could promote direct conversion (reprogramming) of human fibroblasts into neurons when ectopically expressed.
We currently aim to:
1) devise reprogramming strategies to generate human neurons of specific subtypes by directly converting human skin fibroblasts. Our reprogramming paradigm is based on the neurogenic cellular state provided by miR-9/9* and miR-124, and transcription factors that guide the neuronal conversion towards specific subtypes.
2) develop tissue culture models of neurological diseases using patient-specific neurons to study cell autonomous properties associated with the disease state in induced human neurons.
2) identify molecular mechanisms underlying the neurogenic activity of miR-9/9* and miR-124. We use interdisciplinary approaches (molecular genetics, genomics and biochemistry) to delineate how these microRNAs promote neuronal fate. Specifically, we are interested in understanding changes in chromatin remodeling complex activities and changes in chromatin landscape mediated by miR-9/9* and miR-124.

Selected Publications:

Victor, M.B., Richner, M., Hermanstyne, T.O., Ransdell, J.O., Sobieski, C., Deng, P.Y., Klyachko, V.A., Nerbonne, J.M., Yoo, A.S. (2014). Generation of human striatal neurons by microRNA-dependent direct conversion of fibroblasts. Neuron 84, 311-323. (PMCID: PMC4223654)

Abernathy, D.G., and Yoo, A.S. (2014). MicroRNA-dependent genetic networks during neural development. Cell Tissue Res. (PMCID: PMC4247364)

Sun, A.X., Crabtree, G.R., and Yoo, A.S. (2013). MicroRNAs: regulators of neuronal fate. Curr Opin Cell Biol 25, 215-221. (PMCID: PMC3836262)

Yoo AS*, Sun, AX, Li L, Shcheglovitov A, Portmann T, Li Y, Lee-Messer C, Dolmetsch RE, Tsien RW and Crabtree GR.* MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 2011 476: 228-231. *Co-corresponding author (PMCID: 21753754)

Yoo AS, Staahl BT, Chen L and Crabtree GR. MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 2009 460: 642-646. (PMCID: 19561591)

Yoo AS and Crabtree GR. ATP-dependent chromatin remodeling in neural development. Curr Opin Neurobiol 2009 19: 120-126. (PMCID: 19442513)

Yoo AS and Greenwald I. LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science 2005 310:1330-1333. (PMCID: 16239437)

Yoo AS, Bais C and Greenwald I. Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development. Science 2004 303:663-666. (PMCID: 14752159)

Yu H, Yoo AS and Greenwald I. Cluster Analyzer for Transcription Sites (CATS): a C++-based program for identifying clustered transcription factor binding sites. Bioinformatics 2004 20: 1198-1200. (PMCID: 14764556)

Yoo AS, Cheng I, Chung S, Grenfell TZ, Lee H, Pack-Chung E, Handler M, Shen J, Xia W, Tesco G, et al. Presenilin-mediated modulation of capacitative calcium entry. Neuron 2000 27:561-572. (PMCID: 11055438)

Last Updated: 12/5/2014 4:50:42 PM

An example of human neurons converted from dermal fibroblasts
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