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Shawn Xu, PhD

Bernard W. Agranoff Collegiate Professor in the Life Sciences
Professor, Molecular & Integrative Physiology
Research Professor, Life Sciences Institute

Room 6115A Life Sciences Institute
210 Washtenaw Avenue
Ann Arbor, MI 48109-2216

(734) 615-9311

Areas of Interest

We are interested in understanding some of the fundamental questions in neuroscience and physiology: How are sensory inputs perceived by the nervous system, how do neural circuits and synapses process sensory information to generate behavioral output, and how do genes and drugs of abuse regulate these processes?  We also investigate how sensory cues and genes modulate aging and longevity.  To address these questions, we use the genetic model organism C. elegans because of its simple and well characterized nervous system.  We take a multidisciplinary approach combining functional imaging, molecular genetics, behavioral analysis, and electrophysiology.

Sensory transduction and behavior The environment has a profound impact on animal behavior.  The ability to sense environmental cues to adjust its behavior is essential for an animal’s life.  There are five common sensory modalities in mammals: vision, smell, taste, hearing and touch.  In addition, we rely on proprioception, which is often referred to as the sixth sense, to control body posture, balance and movement. Among the most common sensory stimuli are chemicals (smell and taste), mechanical forces (touch, hearing and proprioception), light (vision), and temperature.  We are particularly interested in understanding how sensory neurons detect and transduce mechanical, chemical, and light signals to generate behavioral output, and how gene networks (e.g. receptors, ion channels and signaling molecules) regulate these processes. 

Neural circuits and synaptic mechanisms underlying behavior and drug addiction One of the ultimate goals of neuroscience research is to understand how the nervous system controls behavior.  As neural circuits are the functional units of the nervous system, mapping the functional components of neural circuits and dissecting the synaptic mechanisms by which the circuits process information hold the key to understanding the neural basis of behavior and addiction.  C. elegans has recently emerged as an excellent model for approaching these questions because of its simple and very well characterized nervous system.  We have developed novel tools to quantify behavior and record neural circuit and synaptic activities, which would greatly facilitate the dissection of neural circuit and synaptic mechanisms underlying behavior.  We currently focus on sensory behaviors and drug dependent behaviors.  To do so, we take a multidisciplinary approach combining functional imaging, molecular genetics, behavioral analysis, and electrophysiology.

Sensory and genetic modulation of aging and longevity Sensory cues not only regulate an animal’s behavior but also its physiology, for example, aging and longevity.  In addition to nutrients, other environmental cues, such as thermo- and chemo-sensory inputs, have a profound impact on aging and longevity. For example, both cold- and warm-blooded animals live longer at lower body temperatures, highlighting a general role of temperature in lifespan regulation. However, the underlying mechanisms remain largely unknown.  We have recently identified TRPA1, a cold-sensitive ion channel, as a thermo-sensor that detects temperature decreases in the environment to extend lifespan, demonstrating that genes actively promote longevity at cold temperatures.  This calls into question the century-old view that cold-dependent lifespan extension is a passive thermodynamic process. We are interested in identifying new genes and pathways that mediate temperature-dependent lifespan regulation in C. elegans.  Ultimately, we would like to derive a thorough understanding of how sensory cues modulate aging and longevity. 

 

Selected Publications:

Xiao, R., Zhang, B. *, Dong, Y. *, Gong, J. *, Xu, T., Liu, J., and Xu, X.Z.S. (2013) A genetic program promotes C. elegans longevity via a thermosensitive TRP channel.  Cell  152, 806-817

Piggott, B.J., Liu, J.*, Feng, Z.*, Wescott, S.A., and Xu, X.Z.S. (2011) The neural circuits and synaptic mechanisms underlying motor initiation in C. elegans.  Cell   147, 922-933

Li, W., Piggott, B.J., Feng, Z., and Xu, X.Z.S. (2011) The neural circuits and sensory channels mediating harsh touch sensation in Caenorhabditis elegans.  Nature Communications 2, 315.

Kang, L.*, Gao, J.*, Schafer, W.R., Xie, Z., and Xu, X.Z.S. (2010) C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel.  Neuron 67, 381-391.

Wang, G.J., Kang, L., Kim, J.E., Maro, G.S., Xu, X.Z.S., and Shen, K. (2010) GRLD-1 regulates cell-wide abundance of glutamate receptor through post-transcriptional regulation.  Nature Neuroscience 13, 1489-1495

Liu, J.*, Ward, A.*, Gao, J., Dong, Y., Nishio, N., Inada, H., Kang, L., Yu, Y., Ma., D., Xu, T., Mori, I., Xie, Z., and Xu, X.Z.S. (2010) C. elegans phototransduction requires a G protein-dependent cGMP pathway and a taste receptor homolog.   Nature Neuroscience  13, 715-722

Ward, A.*, Liu, J.*, Feng, Z., and Xu, X.Z.S. (2008) Light-sensitive neurons and channels mediate phototaxis in C. elegans.   Nature Neuroscience  11, 916-922.

Feng, Z.*, Li, W.*, Ward, A., Piggott, B.J., Larkspur, E., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels.  Cell  127, 621-633

Li, W., Feng, Z., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue.   Nature 440, 684-687.

Credentials

Ph.D., Johns Hopkins University, 2000

Published Articles or Reviews

Gong, J., Yuan, Y., Ward, A., Kang, L., Zhang, B., Wu, Z., Peng, J., Feng, Z., Liu, J., and Xu, X.Z.S. (2016) The C. elegans taste receptor homolog LITE-1 is a photoreceptor.  Cell 167, 1252-63.

Wang, X., Li, G., Liu, J., Liu, J., and Xu, X.Z.S. (2016) TMC-1 mediates alkaline sensation in C. elegans via nociceptive neurons.  Neuron  91, 146-54

Li, Z., Liu, J., Zheng, M., and Xu, X.Z.S. (2014) Encoding of both analog- and digital-like behavioral outputs by one C. elegans interneuron.  Cell  159, 751-765.  (cover story)

Xiao, R., Zhang, B., Dong, Y., Gong, J., Xu, T., Liu, J., and Xu, X.Z.S. (2013) A genetic program promotes C. elegans longevity via a thermosensitive TRP channel.  Cell  152, 806-817

Piggott, B.J., Liu, J., Feng, Z., Wescott, S.A., and Xu, X.Z.S. (2011) The neural circuits and synaptic mechanisms underlying motor initiation in C. elegansCell   147, 922-933

Kang, L., Gao, J., Schafer, W.R., Xie, Z., and Xu, X.Z.S. (2010) C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanosensory transduction channel.  Neuron 67, 381-391

Liu, J., Ward, A., Gao, J., Dong, Y., Nishio, N., Inada, H., Kang, L., Yu, Y., Ma., D., Xu, T., Mori, I., Xie, Z., and Xu, X.Z.S. (2010) C. elegans phototransduction requires a G protein-dependent cGMP pathway and a taste receptor homolog.   Nature Neuroscience  13, 715-722

Ward, A., Liu, J., Feng, Z., and Xu, X.Z.S. (2008) Light-sensitive neurons and channels mediate phototaxis in C. elegans.   Nature Neuroscience  11, 916-922.

Feng, Z., Li, W., Ward, A., Piggott, B.J., Larkspur, E., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans model of nicotine-dependent behavior: regulation by TRP-family channels.  Cell  127, 621-633

Li, W., Feng, Z., Sternberg, P.W., and Xu, X.Z.S. (2006) A C. elegans stretch receptor neuron revealed by a mechanosensitive TRP channel homologue.   Nature 440, 684-687.