- Professor of Biological Sciences (Columbia University)
We study two distinct classes of calcium-conducting channels, the voltage-gated calcium channels (VGCCs) and the transient receptor potential (TRP) channels. VGCCs are present in neurons, muscles and other excitable cells, and they open in response to membrane depolarization. They are vital for diverse biological processes including muscle contraction, neurotransmission, neurodevelopment and gene expression. TRP channels are more ubiquitous and are activated by more diverse mechanisms, including intracellular or extracellular ligands, mechanical stretch, temperature as well as changes in membrane voltage. TRP channels are involved in numerous biological processes, and they play an especially important role in taste, touch, olfaction, temperature and pain sensation, and other senses.
Both VGCCs and TRP channels, when open, lead to membrane depolarization and calcium influx; thus, they not only increase cell excitability but also affect cellular calcium signaling. VGCCs mutations and malfunction have been linked to cardiovascular diseases, ataxia, epilepsy, night blindness, migraine and autism, and TRP channel mutations and malfunction have been linked to kidney diseases, cardiovascular diseases, pulmonary diseases, skin diseases, muscle diseases, neurological diseases, mucolipidosis and cancer.
We use a combination of techniques including molecular biology, biochemistry, patch-clamp, X-ray crystallography and optical imaging to study the structure, function, regulation, targeting, localization and activity-dependent trafficking of VGCCs and TRP channels. Our objectives are to better understand how these ion channels work as molecular machines, how they function to control and regulate cell calcium signaling and physiology, and how their mutations and malfunction cause human diseases.
Departments and Divisions
- Department of Biological Sciences (Columbia University)
Fairchild Center1212 Amsterdam Ave
Room 917, Mail Code: 2462
New York, NY 10027
- (212) 854-6161
- Biophysics/Ion Channels
- Cellular/Molecular/Developmental Neuroscience
Yu, Y., Ulbrich, M.H., Li, M-h., Chen, X-Z., Ong, A.C.M., Tong, L., Isacoff, E.Y., and Yang, J. (2009) Structural and molecular basis of the assembly of the TRPP2/PKD1 complex Proc. Natl. Acad. Sci 106: 11558-11563.
Ã¢â‚¬Â¨Zhang, Y., Chen, Y-h., Bangaru, S.D., Abele, K., Tanabe, S., Kozasa, T., and Yang, J (2008) Origin of the voltage-dependence of G protein regulation of P/Q-type Ca2+ channels J. Neurosci. 28: 14176-14188.
Ã¢â‚¬Â¨He., L-l., Zhang, Y., Chen, Y-h., Fitzmaurice, A., and Yang, J (2007) Functional modularity of the beta subunit of voltage-gated Ca2+ channels Biophysical Journal 93: 834-845.
Ã¢â‚¬Â¨Zhen, X-G., Xie, C., Fitzmaurice, A., Schoonover, C. E., Orenstein, E., and Yang, J (2005) Functional architecture of the inner pore of a voltage-gated Ca2+ channel J. Gen. Physiol. 126: 193-204.
Ã¢â‚¬Â¨Xie, C., Zhen, X-G., and Yang, J. (2005) Localization of the activation gate of a voltage-gated Ca2+ channel J. Gen. Physiol. 126: 205-212.
Ã¢â‚¬Â¨Chen, Y-h., Li, M-h., Zhang, Y., He., L-l., Yamada, Y., Fitzmaurice, A., Shen, Y., Zhang, H., Tong, L., and Yang, J. (2004) Structural basis of the alpha1-beta interaction of voltage-gated Ca2+ channels Nature 429: 675-680.