The overall goal of my lab is to investigate how aging in human neurons contributes to the late onset of neurodegeneration in various neurodegenerative disorders. We approach this goal by developing cellular reprogramming approaches by evoking the chromatin switch using microRNAs (miRNAs) as neurogenic effectors that can turn human adult fibroblasts directly to neurons. This process termed direct neuronal reprogramming offers a critical benefit of propagating the age signature stored in pre-reprogrammed cells to directly converted neurons, thereby mimicking neurons of adult individuals. We use interdisciplinary approaches (molecular genetics, genomics, and biochemistry) to meet our research goals in two broad areas:
- Modeling adult-onset neurodegenerative diseases using patient-derived neurons and delineating pathogenic mechanisms associated with neuron-intrinsic, age-associated vulnerability to neurodegeneration
- Identify molecular mechanisms underlying the neurogenic activity of microRNAs via inducing the reconfiguration of chromatin landscape
Education and Training
2011 – Postdoctoral fellow, Stanford University, CA, Chromatin biology and cell fate reprogramming
2005 – Ph.D. Columbia University, NY, Cellular, Molecular and Biophysical Studies
1998 – M.Sc. University of British Columbia, Vancouver, BC, Canada, Experimental Medicine (Neurology)
1995 – B.Sc. McGill University, Montreal, PQ, Canada, Physiology (with focus on Neurophysiology)
07/2022 – present – Professor, Department Developmental Biology, Washington University School of Medicine
08/2018 – 06/2022 – Associate Professor, Department Developmental Biology, Washington University School of Medicine
August 2011 – 2018 – Assistant Professor, Department Developmental Biology, Washington University School of Medicine
Honors and Awards
WUSM Distinguished Investigator Award, 2018
Presidential Early Career Award for Scientist and Engineers (PECASE), 2013
NIH Director’s New Innovator Award, 2012-2017
Ellison Medical Foundation New Investigator in Aging Award, 2012-2016
Mallinckrodt Foundation New Investigator Award, 2011-2013
Helen Hay Whitney Foundation Fellowship, 2007-2010
Natural Sciences and Engineering Research Council of Canada (NSERC) Postgraduate Award (for tenure at universities outside Canada), 2001-2003
Honors in Neurophysiology, McGill University, 1995
- Oh YM*, Lee SW*, Kim WK, Chen S, Church VA, Cates K, Li T, Zhang B, Dolle RE, Dahiya S, Pak SC, Silverman GA, Perlmutter DH, Yoo AS. Age-related Huntington’s disease progression modeled in directly reprogrammed patient-derived striatal neurons highlights impaired autophagy. Nature Neuroscience. 2022 Nov;25(11):1420-1433. doi: 10.1038/s41593-022-01185-4. Epub 2022 Oct 27. PMID: 36303071. *equal contribution
- Capano LS*, Sato C*, Ficulle E*, Yu A*, Horie K, Kwon J-S, Burbach KF, Barthélemy NR, Fox SG, Karch CM, Bateman RJ, Houlden H, Morimoto RI, Holtzman DM, Duff KE, and Yoo AS. Recapitulation of endogenous 4R tau expression and formation of insoluble tau in directly reprogrammed human neurons. Cell Stem Cell. 2022 Jun 2; 29(6):918-932. doi: 10.1016/j.stem.2022.04.018. PMID: 35659876. *equal contribution
- Lu YL, Liu Y, McCoy MJ, Yoo AS. MiR-124 synergism with ELAVL3 enhances target gene expression to promote neuronal maturity. Proc Natl Acad Sci USA. 2021 Jun 1;118(22):e2015454118. doi: 10.1073/pnas.2015454118.
- Cates K*, McCoy MJ*, Kwon JS*, Liu Y*, Abernathy DG, Zhang B, Liu S, Gontarz P, Kim WK, Chen S, Kong W, Ho JN, Burbach KF, Gabel HW, Morris SA, Yoo AS. Deconstructing Stepwise Fate Conversion of Human Fibroblasts to Neurons by MicroRNAs. Cell Stem Cell. 2020 Sep 17:S1934-5909(20)30411-2. *: Co-first authors
- Lee, S.W., Oh, Y.M., Lu, Y.L., Kim, W.K., Yoo, A.S. (2018). MicroRNAs Overcome Cell Fate Barrier by Reducing EZH2-Controlled REST Stability during Neuronal Conversion of Human Adult Fibroblasts. Dev. Cell 46(1):73-84.e7. doi: 10.1016/j.devcel.2018.06.007.
- McCoy, M.J.^, Paul, A.J.^, Victor, M.B., Richner, M., Gabel, H.W., Gong, H., Yoo, A.S.*, Ahn, T.H.* (2018). LONGO: an R package for interactive gene length dependent analysis for neuronal identity. Bioinformatics 34(13):i422-i428. doi: 10.1093/bioinformatics/bty243. *: co-corresponding authors, ^: co-first authors
- Victor, M.B., Richner, M., Olsen, H.E., Lee, S.W., Monteys, A.M., Ma, C., Huh, C.J., Zhang, B., Davidson, B.L., Yang, X.W., Yoo, A.S. (2018). Striatal neurons directly converted from Huntington’s disease patient fibroblasts recapitulate age-associated disease phenotypes. Nature Neuroscience 3:341-352 doi: 10.1038/s41593-018-0075-7.
- Abernathy, D.G.*, Kim, W.K.*, McCoy, M.J.*, Lake, A.M., Ouwenga, R., Lee, S.W., Xing, X., Li, D., Lee, H.J., Heuckeroth, R.O., Dougherty, J.D., Wang, T., Yoo, A.S. (2017). MicroRNAs Induce a Permissive Chromatin Environment that Enables Neuronal Subtype-Specific Reprogramming of Adult Human Fibroblasts. Cell Stem Cell 21, 332-348. *: co-first authors
- Huh, C.J., Zhang, B, Victor, M.B., Dahiya, S., Batista, L.F., Horvath, S., and Yoo, A.S. (2016). Maintenance of age in human neurons generated by microRNA-based neuronal conversion of fibroblasts. eLife 5:e18648.
- Richner, M.*, Victor, M.B.*, Liu, Y., Abernathy, D., and Yoo, A.S. (2015). MicroRNA-based conversion of human fibroblasts into striatal medium spiny neurons. Nature Protocols 10, 1543-1555. *: co-first authors
- 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. *: co-first authors [Featured in Neuron Best of 2014-2015]
- Yoo, A.S.*, Sun, A.X., Li, L., Shcheglovitov, A., Portmann, T., Li, Y., Lee-Messer, C., Dolmetsch, R.E., Tsien, R.W., and Crabtree, G.R.* (2011). MicroRNA-mediated conversion of human fibroblasts to neurons. Nature 476, 228-231. *: corresponding authors
- Yoo, A.S., Staahl, B.T., Chen, L., and Crabtree, G.R. (2009). MicroRNA-mediated switching of chromatin-remodelling complexes in neural development. Nature 460, 642-646.
- Yoo, A.S., and Greenwald, I. (2005). LIN-12/Notch activation leads to microRNA-mediated down-regulation of Vav in C. elegans. Science 310, 1330-1333.
- Yoo, A.S., Bais, C., and Greenwald, I. (2004). Crosstalk between the EGFR and LIN-12/Notch pathways in C. elegans vulval development. Science 303, 663-666.
- Yu, H., Yoo, A.S.*, and Greenwald, I. (2004). Cluster Analyzer for Transcription Sites (CATS): a C++-based program for identifying clustered transcription factor binding sites. Bioinformatics 20, 1198-1200. *: corresponding author
- Yoo, A.S., Cheng, I., Chung, S., Grenfell, T.Z., Lee, H., Pack-Chung, E., Handler, M., Shen, J., Xia, W., Tesco, G., et al. (2000). Presenilin-mediated modulation of capacitative calcium entry. Neuron 27, 561-572.