Search Site

Hynek Wichterle, PhD

Academic Appointments

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

Current Administrative Positions

  • Co-Director, Motor Neuron Center
Hynek Wichterle, PhD

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.

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 inducible expression of transgenes to decode transcriptional programs controlling progressive transitions from a pluripotent stem cell to a defined postmitotic neuron.  We are constructing a global map of genomic sites bound by cell type specific combinations of transcription factors and study how these regulatory elements control expression of distal genes. The ultimate goal is to use stem cell technologies to decipher the syntax and grammar of the "language" used by transcription factors to specify neuronal cell identity during embryonic development.

Finally, the lab  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 for these currently untreatable, devastating conditions.

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

Departmental Appointments

  • Department of Neuroscience
  • Department of Pathology & Cell Biology
  • Department of Rehabilitation and Regenerative Medicine

Lab Locations

Research Interests

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

NIH Grants

  • RNA REGULATORY NETWORKS IN MOTOR NEURON DEVELOPMENT AND FUNCTION (Federal Gov)

    Jul 1 2015 - Apr 30 2020

    SELECTIVE VULNERABILITY OF MOTOR NEURONS IN ALS - PHASE II (Private)

    Apr 1 2016 - Mar 31 2019

    DEVELOPING MOTOR-NEURON DRIVEN REPORTER INDUCED PLURIPOTENT STEM CELLS (IPSC) LINES (Private)

    Oct 14 2016 - Oct 13 2018

    THE ROLE OF PLD1 AND PLD2 IN NEURODEGENERATIVE PATHWAYS COMMON TO ALS AND AD (Private)

    Mar 7 2016 - Mar 6 2018

    STABLE SILENCING OF SPINAL MOTOR NEURON ENHANCERS BY TRANSIENTLY EXPRESSED NKX2.2 (Federal Gov)

    Feb 1 2015 - Jan 31 2018

    EXPLORING SYNAPTIC ABNORMALITIES THAT UNDERLIE HYPERACTIVITY IN A STEM-CELL DERIVED MODEL OF AMYOTROPHIC LATERAL SCLEROSIS (Federal Gov)

    Jan 1 2016 - Dec 31 2017

    MOTOR NEURON SELECTOR GENES AND MECHANISM OF THEIR ACTION (Federal Gov)

    Sep 1 2012 - Jul 31 2017

    PROSPECTIVE PURIFICATION OF ADULT STEM CELL ASTROCYTES (Federal Gov)

    Sep 1 2011 - May 31 2017

    IMPROVING DRUG SCREENING METHODS IN ALS AND IDENTIFYING THERAPEUTIC TARGETS (Private)

    Apr 1 2016 - Mar 31 2017

    GENOME-WIDE MAPPING OF TRANSCRIPTION FACTOR INTERACTIONS DURING STEM CELL TO MOTOR NEURON PROGRAMMING (Private)

    Apr 1 2014 - Mar 31 2017

    CHARACTERIZATION OF PHYSIOLOGICAL PHENOTYPES IN STEM CELL DERIVED ALS MOTOR NEURONS (Private)

    Feb 1 2015 - Jan 31 2017

    MOLECULAR MECHANISMS OF IDH1-MEDIATED GLIOMAGENESIS (Federal Gov)

    Sep 30 2012 - Jan 31 2017

    A CELL-BASED ASSAY TO IDENTIFY NEUROPROTECTIVE MOLECULES FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS (Federal Gov)

    Sep 30 2013 - Sep 29 2016

    NOVEL THEREPEUTIC TARGETS IN ALS DEDUCED FROM MECHANISMS OF SELECTIVE MOTOR NEURON VULNERABILITY AND RESISTANCE (Private)

    Dec 14 2012 - Jun 30 2016

    MICRORNA REGULATION OF ADULT NEURAL STEM CELLS (NY State Gov)

    Mar 1 2013 - Feb 29 2016

    MICRORNA REGULATION OF ADULT NEURAL STEM CELLS (NY State Gov)

    Mar 1 2013 - Feb 28 2016

    MICRORNA REGULATION OF ADULT NEURAL STEM CELLS (NY State Gov)

    Mar 1 2013 - Feb 28 2016

    OCULOMOTOR RESISTANCE IN ALS (Private)

    Jan 1 2013 - Dec 31 2015

    NOVEL THEREPEUTIC TARGETS IN ALS DEDUCED FROM MECHANISMS OF SELECTIVE MOTOR NEURON VULNERABILITY AND RESISTANCE (Private)

    Dec 14 2012 - Dec 13 2015

    NOVEL THEREPEUTIC TARGETS IN ALS DEDUCED FROM MECHANISMS OF SELECTIVE MOTOR NEURON VULNERABILITY AND RESISTANCE (Private)

    Dec 14 2012 - Dec 13 2015

    REGULATING THE DIRECTED DIFFERENTIATION OF CNS AND PANCREATIC ISLET CELL POPULATIONS (NY State Gov)

    Mar 1 2013 - Feb 28 2015

    THREE DIMENSIONAL HIGH RESOLUTION RECONSTRUCTION OF THE INVIVO ADULT NEURAL STEM CELL NICHE (NY State Gov)

    Mar 1 2013 - Feb 28 2015

    THE ROLE OF MIR-17~92 CLUSTER IN MOTOR NEURON DEGENERATION (Federal Gov)

    May 1 2012 - Apr 30 2014

    GENERATION AND CHARACTERIZATION OF AMYOTROPHI (Federal Gov)

    Jul 1 2012 - Sep 30 2013

    SPINAL MUSCULAR ATROPHY (SMA): DISEASE PHENOTYPE AND MECHANISMS (Federal Gov)

    Aug 1 2009 - Aug 31 2013

    P2 ALS INITIATIVE: OCULOMOTOR COLLABORATION AND MOUSE ES WORK (Private)

    Jan 1 2011 - Jun 30 2013

    THREE DIMENSIONAL HIGH RESOLUTION RECONSTRUCTION OF THE INVIVO ADULT NEURAL STEM CELL NICHE (NY State Gov)

    Mar 1 2013 - May 31 2013

    TRANSCRIPTIONAL DETERMINANTS OF MOTOR NEURON IDENTITY (Federal Gov)

    Sep 15 2006 - Feb 28 2013

    HUMAN IPS CELLS AS A MODEL TO STUDY ALS PATHOGENESIS (NY State Gov)

    Jan 1 2009 - Dec 31 2012

    ESTABLISHMENT OF SEGMENTAL IDENTITY IN EMBRYONIC STEM CELL D ERIVED MOTOR MEURONS (Federal Gov)

    Jul 15 2007 - Mar 31 2012

    LINKING GENETIC PROGRAMS OF DIVERSITY TO ES CELL MOTOR NEURO N CONNECTIVITY (Private)

    Sep 1 2008 - Aug 31 2010

    STUDY OF MOTOR NEURON SPECIFIC FUNCTIONS OF SMN PROTEIN IN THE CONTEXT OF EMBRYONIC STEM CELL-DERIVED (Private)

    Feb 1 2006 - Jan 31 2008

Publications

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.

Novitch, B. G., Wichterle, H., Jessell, T. M., and Sockanathan, S. (2003). A requirement for retinoic acid-mediated transcriptional activation in ventral neural patterning and motor neuron specification. Neuron 40, 81-95.

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.

For a complete list of publications, please visit PubMed.gov