Departments And Divisions
- Department of Pathology & Cell Biology
- Department of Neuroscience
- Department of Rehabilitation and Regenerative Medicine
- Associate Professor of Pathology & Cell Biology
- Associate Professor of Neuroscience (in Neurology)
- Associate Professor of Rehabilitation and Regenerative Medicine
- Co-Director, Motor Neuron Center
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.
- 630 West 168th Street
New York, NY 10032
- (212) 342-3929
- Neural Degeneration and Repair
- Cell Specification and Differentiation
- Stem Cell Biology
- Cellular/Molecular/Developmental Neuroscience
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