Christopher E. Henderson, Ph.D.Professor, Pathology & Cell Biology, Neuroscience, Neurology
Co-Director, Motor Neuron Center
Tel +1 212-342-4086
Area of Research
Cell Specification and Differentiation, Neural Degeneration and Repair, Motor Systems, Stem Cell Biology
Motor neuron development and pathology.
Chris Henderson joined the Center for Neurobiology and Behavior in May, 2005. In addition to establishing his own laboratory, he helped to found the Motor Neuron Center, which has strengthened interactions between basic scientists and clinicians on the campus interested in the motor neuron diseases ALS (amyotrophic lateral sclerosis) and SMA (spinal muscular atrophy).
Work in the lab focuses on the study of motor neuron development as an approach to understanding and analyzing mechanisms underlying ALS and SMA. For example, our study of the signaling pathways involved in motor neuron death during development has brought to light a novel mechanism potentially involved in ALS. In a complementary manner, purified motor neurons in culture have allowed us to identify not only polypeptide neurotrophic factors required for normal motor neuron survival, but also compounds from chemical libraries that can enhance neuronal survival or axon growth.
Projects in the laboratory use in vitro and in vivo approaches to study development and pathological mechanisms and to identify novel therapeutic targets. In particular, we are working at the interfaces between developmental biology, chemistry and pathology to study:
* the development and degeneration of specific groups ("pools") of motor neurons, such as those involved in breathing and eye movement
* new mechanisms and pathways involved in neuronal survival and axonal growth or regeneration
* motor neurons derived from patient-specific human stem cells as tools for mechanistic analysis and drug screening in ALS and SMA
Our aim is to move each project forward to the stage where it not only provides new biological insights but can also serve as the basis for development of new therapeutic strategies. Such translational research is catalyzed by the presence in the lab of a neuronal robotic screening platform, and by interactions with clinicians and biotech specialists within the Center and at CUMC.
Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., Wichterle, H., Henderson, C.E., and Eggan, K. (2008). Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons. Science 321: 1218-1221.
Chauvet, S., Cohen, S., Yoshida, Y., Fekrane, L., Livet, J., Gayet, O., Segu, L., Buhot, M.C., Jessell, T.M., Henderson, C.E., and Mann, F. (2007). Gating of Sema3E/PlexinD1 signaling by neuropilin-1 switches axonal repulsion to attraction during brain development. Neuron 56: 807-822.
Raoul, C., Abbas-Terki, T., Bensadoun, J.C., Guillot, S., Haase, G., Szulc, J., Henderson, C.E., and Aebischer, P. (2005). Lentiviral-mediated silencing of SOD1 through RNA interference retards disease onset and progression in a mouse model of ALS. Nat Med 11: 423-428.
Raoul, C., Estevez, A.G., Nishimune, H., Cleveland, D.W., deLapeyriere, O., Henderson, C.E., Haase, G., and Pettmann, B. (2002). Motoneuron death triggered by a specific pathway downstream of Fas. potentiation by ALS-linked SOD1 mutations. Neuron 35: 1067-1083.
Livet, J., Sigrist, M., Stroebel, S., De Paola, V., Price, S.R., Henderson, C.E., Jessell, T.M., and Arber, S. (2002). ETS gene Pea3 controls the central position and terminal arborization of specific motor neuron pools. Neuron 35: 877-892.
Henderson, C.E., Phillips, H.S., Pollock, R.A., Davies, A.M., Lemeulle, C., Armanini, M., Simmons, L., Moffet, B., Vandlen, R.A., Simmons, L.C., Moffet, B., Vandlen, R.A., Koliatsos, V.E., and Rosenthal, A. (1994). GDNF: a potent survival factor for motoneurons present in peripheral nerve and muscle. Science 266: 1062-1064.