Faculty Profile

Fields of Study

Sensory Neurobiology and Integrative Physiology

Areas of Focus

Cell Biology
Development
Neurobiology & Animal Physiology

Research Interest

We are interested in understanding the physiological and pathological functions of Transient Receptor Potential (TRP) ion channels and Ca2+ signaling.

About Haoxing Xu

The major interest in my lab is to understand the transmembrane signaling mechanisms used by cells to detect environmental information and intercellular signals at the molecular, cellular, and system 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. We have recently discovered TRPV3, a novel Ca2+-permeable ion channel that is expressed in the skin, tongue, and sensory neurons. We are currently studying activation mechanisms and in vivo functions of TRPV3.  Another recent focus of the lab is the mucolipin TRP channels. TRPML proteins are predicted to encode ion channels of intracellular endosomes and lysosomes.  We are currently investigating activation mechanisms and in vivo functions  of TRPML channels.

Dr. Xu received his BS from Peking University (Beijing, China) and Ph.D. from Georgia State University in Atlanta, Georgia. He was a postdoctoral fellow (HHMI) in David Clapham's laboratory at Children's Hospital, Harvard Medical School in Boston, Massachusetts.

 

 

Postdoc positions open, please contact Dr. Xu for details.

 

Publications

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. Read Publication.

Xu, H. *, Delling, M. *, Li, L*, Dong, X., and Clapham, DE (2007). "Activating mutation in a mucolipin transient receptor potential channel leads to melanocyte loss in varitint–waddler mice." Proceedings of the National Academy of Sciences (USA) 2007, Nov 13;104(46):18321-6. Epub 2007 Nov 7. Read Publication.

Xu, H., Delling, M., Jun, JC, and Clapham, DE (2006). "Oregano, Thyme, and Clove-derived Flavors and Skin Sensitizers Activate Specific TRP Channels." Nature Neuroscience 2006 May; 9(5):628-635. Read Publication.

Xu, H.*, Blair, NT.*, and Clapham, DE (2005). "Camphor Activates and Strongly Desensitizes TRPV1 in a Vanilloid-independent Mechanism." The Journal of Neuroscience 2004; 25(39): 8924-37. The work was highlighted in The Journal of neuroscience, 2005 Sep 28; 25(39), Nature, 2005 Oct 13; 437: 930-931, and Nature Reviews Neuroscience, 2005, 6: 826 Read Publication.

Zhuang, ZY., Xu, H., Clapham, DE., and Ji, RR (2004). "Phosphatidylinositol 3-kinase activates ERK in primary sensory neurons and mediates inflammatory heat hyperalgesia through TRPV1 sensitization." The Journal of Neuroscience 2004; 24(38):8300-9. Read Publication.

Ito, M.*, Xu, H.*, Guffanti, A., Wei, Y., Zvi, L., Clapham, DE., and Krulwich, TA (2004). "The voltage-gated Na+ channel NaVBP has a role in motility, chemotaxis and pH homeostasis of an alkaliphilic Bacillus." Proceedings of the National Academy of Sciences 2004; 101(29): 10566-71. Epub 2004 Jul 08. Read Publication.

Moran, MM., Xu, H. and Clapham, DE (2004). "TRP ion channels in the nervous system." Current Opinion in Neurobiology 2004; 14(3): 362-9. Read Publication.

Xu, H.*, Jin, J.*, DeFelice, LJ., Andrews, NC., and Clapham, DE (2004). "A spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway." PLoS Biology 2004 Mar;2(3):E50. Epub 2004 Mar 16 Synopsis can be found at PLoS Biol. 2004 Mar;2(3):E70. Epub 2004 Mar 16. Read Publication.

Koishi, R.*, Xu, H.*, Ren D., Navarro B., Spiller BW., Shi Q., and Clapham, DE. (2004). "A superfamily of voltage-gated sodium channels in bacteria." Journal of Biological Chemistry 279(10):9532-8. Epub 2003 Dec 09. Read Publication.

Xu, H.*, Ramsey, IS.*, Kotecha, SA.*, Moran, MM., Chong, JA., Curtis, R., DiStefano, PS., Silos-Santiago, I., Xie, Y., Lawson, D., Ge, P., Lilly, J., and Clapham, DE. (2002). "TRPV3 is a calcium-permeable temperature-sensitive cation channel." Nature 418, 181-186, . published online 23 June 2002; doi:10.1038/nature00882. Comments about this work and other groups' related articles see "Breakthrough of The Year" by Science, Vol 298, Issue 5602, 2297-2303, 20 December 2002. Read Publication.

Ren, D.*, Navarro, B.*, Xu, H.*, Yue, L.*, Shi, Q., and Clapham, DE (2001). "A prokaryotic voltage-gated sodium channel." Science Dec 14 2001: 2372-2375. Perspectives about this paper can be found in Science, 294: 2306-2308. Read Publication.

Xu, H., Wu, J., Cui, N., Abdulkadir, L., Wang, R., Mao, J., Giwa, LR., Chanchevalap, S., and Jiang, C. (2001). "Distinct histidine residues control the acid-induced activation and inhibition of the cloned KATP channel." Journal of Biological Chemistry 276, 38690-38696. .

Xu, H.*, Cui, N.*, Yang, Z., Wu, J., Giwa, LR., Abdulkadir, L., Sharma, P., and Jiang, C. (2001). "Direct activation of KATP channels by intracellular acidosis." Journal of Biological Chemistry 276, 12898-12902. .

Xu, H.*, Yang, Z.*, Cui, N., Valesky, WW., and Jiang, C. (2000). "A single residue responsible for the difference of Kir4.1 channel from Kir1.1 in pH-sensitivity, rectification and single channel conductance." Journal of Physiology (London) 528.2, pp. 267-277. .

Xu, H., Yang, Z., Cui, N., Giwa, LR., Abdulkadir, L., Patel, M., Sharma, P., Shan, G., Shen W., and Jiang C. (2000). "Molecular determinants for the distinct pH sensitivity of Kir1.1 and Kir4.1." American Journal of Physiology 279: C1464-C1471.

Xu, H., Cui, N., Yang, Z., Qu, Z., and Jiang, C. (2000). "Modulation of Kir4.1 and Kir5.1 by hypercapnia and intracellular acidosis. ." Journal of Physiology (London) 524, 725-735.

* Co-first author