Ph.D. Georgia State University.
B.S. Peking University, China.
The major interest in our lab is to understand how Ca2+ flux pathways, i.e, Ca2+-pemeant channels, at the cell surface and in intracellular organelles are precisely controlled (gated) by extracellular and intracellular signals, and how this information is transduced into physiological and pathological changes at the cellular and organismal levels. We use an integrative approach with state-of-art techniques including molecular biology, bioinformatics, biochemistry, immunochemistry, electrophysiology, fluorescence imaging, confocal microscopy, and mouse genetics. A current focus is TRP channels, a large superfamily of transmembrane proteins serving as molecular/cellular sensors for a variety of physiological/pathological functions. Mucolipin TRP (TRPML) proteins encode ion channels of intracellular endosomes and lysosomes; human mutations of TRPML1 cause type IV mucolipidosis lysosome storage disease. Using TRPML knockout and transgenic mice, we are currently investigating activation mechanisms and in vivo functions of TRPML channels. Another recent focus is TRPV3, a novel Ca2+-permeable ion channel that we recently discovered and is expressed in the skin; human mutations of TRPV3 cause skin diseases. Using TRPV3 knockout and transgenic mice, we are currently studying activation mechanisms and in vivo functions of TRPV3.
Shen, D., Wang, X., Li, X., Zhang, X., Yao, Z, Dibble, S., Dong, X.P, Yu, T, Lieberman A.P, Showalter, H.D., and Xu, H (2012). "Lipid storage disorders block lysosomal trafficking by inhibiting TRP channel and calcium release." Nature Communications 3 : 731 doi: 10.1038/ncomms1735 .
Jin J, Wu LJ, Jun J, Cheng X, Xu H, Andrews NC, Clapham DE (2011). "The channel kinase, TRPM7, is required for early embryonic development." PNAS ePub Dec 27, 2011.
Dong, XP.*, Shen, D.*, Wang, X.*, Dawson, T., Li, X., Zhang, Q., Cheng, X., Zhang, Y., Weisman, L., Delling, M., and Xu, H (2010). "PI(3,5)P2 controls membrane trafficking by direct activation of mucolipin Ca2+ release channels in the endolysosome." Nature Communications 1:38 doi: 10.1038/ncomms1037.
Cheng, X.*, Jin, J.*, Hu, L., Shen, D., Dong, X., Samie, M.A, Knoff, J., Eisinger, B., Liu, M., Huang, S.M., Caterina, M.J., Dempsey, P., Michael, L.E., Dlugosz, A., Andrews, N., Clapham DE, and Xu, H. (2010). "TRP Channel Regulates EGFR Signaling in Hair Morphogenesis and Skin Barrier Formation ." Cell 141. 331-343
Dong, X.*, Wang,X.*, Shen,D.*,Chen, S., Liu, M., Wang, Y., Mills, E.,Cheng, X., Delling, M., and Xu, H. (2009). "Activating mutations of the TRPML1 channel revealed by proline scanning mutagenesis." J. Biol. Chem. 10.1074/jbc.M109.037184.
Dong, X, Cheng, X., Mills, E., Delling, M., Wang, F., Kurz, T. and Xu, H. (2008). "The Type IV Mucolipidosis-Associated Protein TRPML1 is an Endo-lysosomal Iron Release Channel." Nature 2008, advance online publication, doi:10.1038/nature07311.