Hynek Wichterle, PhD

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Overview

Hynek Wichterle is an associate professor holding a joint appointment in the Departments of Pathology & Cell Biology and Neuroscience (in Neurology) at Columbia University Medical center. He received his M.S. degree from Charles University in Prague and his Ph.D. degree from The Rockefeller University. He trained at Columbia University, where he became assistant professor in 2004 and associate professor in 2012. He serves as a co-director of the Columbia Stem Cell Initiative and as a Vice-Chief of the Division of Regenerative Medicine in the Department of Rehabilitation & Regenerative Medicine.

Email: hw350@cumc.columbia.edu

Academic Appointments

  • Professor of Pathology & Cell Biology
  • Professor of Neuroscience (in Neurology)
  • Professor of Rehabilitation and Regenerative Medicine

Administrative Titles

  • Co-Director, Motor Neuron Center

Gender

  • Male

Research

Cell Specification & Differentiation; Neural Degeneration & Repair; Stem Cell Biology

My laboratory models and studies the development of the nervous system in a culture dish. We have pioneered some of the most efficient methods for the differentiation of pluripotent embryonic stem cells into specific subtypes of spinal motor neurons and interneurons in vitro. The process faithfully recapitulates normal embryonic development, providing a unique opportunity to study neural development at a biochemical level in a controlled environment outside of the embryo.

We combine the differentiation system with CRISPR based genome editing and with inducible transgene expression to decode transcriptional programs controlling progressive transitions from a pluripotent stem cell to a defined postmitotic neuron. We assembled a global map of genomic regulatory elements controlling motor neuron expression program. Our ultimate goal is to decipher the syntax and grammar of the "language" used by transcription factors to specify neuronal cell identity during embryonic development.

The lab also capitalizes on the unlimited source of spinal neurons to study molecular processes underlying neuronal maturation, synapse formation, and neuronal aging and degeneration. We are using both mouse and human pluripotent stem cells to model motor neuron degenerative diseases, such as amyotrophic lateral sclerosis (ALS or Lou Gehrig’s disease), with the goal of discovering new drugs that promote motor neuron survival.

Research Interests

  • Cell Specification and Differentiation
  • Cellular/Molecular/Developmental Neuroscience
  • Neural Degeneration and Repair
  • Stem Cell Biology

Selected Publications

  • Closser, M., Guo, Y., Wang, P., Patel, T., Jang, S., Hammelman, J., Nooij, J.D., Kopunova, R., Mazzoni, E.O., Ruan, Y., Gifford, D., and Wichterle, H. (2021). An expansion of the non-coding genome and its regulatory potential underlies vertebrate neuronal diversity. Neuron, 2021.
  • Bos PH, Lowry ER, Costa J, Thams S, Garcia-Diaz A, Zask A, Wichterle H, Stockwell BR. Development of MAP4 Kinase Inhibitors as Motor Neuron-Protecting Agents. Cell Chem Biol. 2019 Dec 19;26(12):1703-1715.e37. doi: 10.1016/j.chembiol.2019.10.005. Epub 2019 Oct
  • Thams S, Lowry ER, Larraufie MH, Spiller KJ, Li H, Williams DJ, Hoang P, Jiang E, Williams LA, Sandoe J, Eggan K, Lieberam I, Kanning KC, Stockwell BR, Henderson CE, Wichterle H. A Stem Cell-Based Screening Platform Identifies Compounds that Desensitize Motor Neurons to Endoplasmic Reticulum Stress. Mol Ther. 2019 Jan 2;27(1):87-101. doi: 10.1016/j.ymthe.2018.10.010. Epub 2018 Oct 19.
  • Hoang PT, Chalif JI, Bikoff JB, Jessell TM, Mentis GZ, Wichterle H. Subtype Diversification and Synaptic Specificity of Stem Cell-Derived Spinal Interneurons. Neuron. 2018 Oct 10;100(1):135-149.e7. doi: 10.1016/j.neuron.2018.09.016.
  • Jacko M, Weyn-Vanhentenryck SM, Smerdon JW, Yan R, Feng H, Williams DJ, Pai J, Xu K, Wichterle H, Zhang C. Rbfox Splicing Factors Promote Neuronal Maturation and Axon Initial Segment Assembly. Neuron. 2018 Feb 21;97(4):853-868.e6. doi: 10.1016/j.neuron.2018.01.020. Epub 2018 Feb 1. PMID: 29398366
  • Rhee, H.S., Closser, M., Guo, Y., Bashkirova, E.V., Tan, G.C., Gifford, D.K., and Wichterle, H. (2016). Expression of Terminal Effector Genes in Mammalian Neurons Is Maintained by a Dynamic Relay of Transient Enhancers. Neuron 92, 1252-1265.
  • Tan GC, Mazzoni EO, Wichterle H. Iterative Role of Notch Signaling in Spinal Motor Neuron Diversification. Cell Rep. 2016 Jul 26;16(4):907-16.
  • Mazzoni, E.O., Mahony, S., Closser, M., Morrison, C.A., Nedelec, S., Williams, D.J., An, D., Gifford, D.K., and Wichterle, H. (2013a). Synergistic binding of transcription factors to cell-specific enhancers programs motor neuron identity. Nature neuroscience 16, 1219-1227.
  • Mazzoni, E.O., Mahony, S., Peljto, M., Patel, T., Thornton, S.R., McCuine, S., Reeder, C., Boyer, L.A., Young, R.A., Gifford, D.K., and Wichterle, H. (2013b). Saltatory remodeling of Hox chromatin in response to rostrocaudal patterning signals. Nature neuroscience 16, 1191-1198.
  • Amoroso, M.W., Croft, G.F., Williams, D.J., O'Keeffe, S., Carrasco, M.A., Davis, A.R., Roybon, L., Oakley, D.H., Maniatis, T., Henderson, C.E., and Wichterle, H. (2013). Accelerated High-Yield Generation of Limb-Innervating Motor Neurons from Human Stem Cells. J Neurosci 33, 574-586.
  • Nedelec, S., Peljto, M., Shi, P., Amaroso, M., Kam, L, and Wichterle, H. Concentration dependent requirement for local protein synthesis in motor neuron subtype specific response to axon guidance cues. J Neurosci. 2012;32(4):1496-506.
  • Chen, J. A., Huang, Y. P., Mazzoni, E. O., Tan, G. C., Zavadil, J., Wichterle, H., 2011. Mir-17-3p controls spinal neural progenitor patterning by regulating olig2/irx3 cross-repressive loop. Neuron. 69, 721-35.
  • Peljto, M., Dasen, J.S., Mazzoni, E.O., Jessell, T.M., and Wichterle, H. (2010). Functional diversity of ESC-derived motor neuron subtypes revealed through intraspinal transplantation. Cell Stem Cell 7, 355-366.
  • Wichterle, H., Lieberam, I., Porter, J. A., and Jessell, T. M. (2002). Directed differentiation of embryonic stem cells into motor neurons. Cell 110, 385-397.