David E. Clapham,M.D., Ph.D.
Department of Neurobiology and Pediatrics,
Room 1309, Enders Building,
320 Longwood Avenue, Boston, MA 02115
tel: (617) 919-2680; fax: (617) 731-0787
My laboratory studies ion channels. More detail is described at http://clapham.tch.harvard.edu/.
Our research is currently focused on discovering new ion channels that mediate Ca2+ entry across the plasma membrane and the mechanisms by which these channels are controlled by signal transduction pathways. To carry out these goals, we employ patch clamp, confocal microscopy, and total internal reflectance microscopy, in conjunction with molecular biology, cell biology, and biochemical approaches.
Recently we have expressed a bacterial sodium-selective ion channel in mammalian cells and studied its gating properties. We have crystallized the protein and are in the process of obtaining high-resolution structure that should yield important information on sodium selectivity and the voltage gate.
Finally, we succeeded in patch clamping mitochondrial inner membrane and described a highly calcium-selective ion channel.
Selected Calcium Signaling Publications:
Kirichok, Y., Navarro, B., and Clapham, D.E. (2006). Whole-cell patch clamp measurements of spermatozoa reveal an alkaline-activated Ca2+ channel. Nature 439(7077): 737-740.
Ramsey, I.S., Moran, M.M., Chong, J.A., and Clapham, D.E. (2006). A voltage-gated proton-selective channel lacking the pore domain. Nature 440(7088): 1213–1216.
Xu, H., Delling, M., Jun, J., and Clapham, D.E. (2006). Flavors and skin sensitizers activate specific TRP channels. Nature Neuroscience 5: 628-635.
Krapivinsky, G., Mochida, S., Krapivinsky, L., Cibulsky, S.M., and Clapham, D.E. (2006). The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release. Neuron 52: 485-496.
Qi, H., Moran, M.M., Navarro, B., Chong, J.A., Krapivinsky, G., Krapivinsky, L., Kirichok, Y., Ramsey, I.S., Quill, T.A., and Clapham, D.E. (2007). All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proc. Natl. Acad. Sci. USA 104(4): 1219-1223.
Xu, H., Delling, M., Li, Linyu, and Clapham, D.E. (2007). Activating mutation in a mucolipin TRP channel leads to melanocyte loss in varitint-waddler mice. Proc. Natl. Acad. Sci. USA 104(46): 18321-18326.
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