Dr SZ. Xu's laboratory is focused on novel calcium channels and their functions in human diseases, especially calcium-permeable ion channels in the development of cardiovascular diseases and diabetes. For example, the TRPC channels and store-operated channels ORAI/STIM. Using patch clamp and cell models overexpressing individual channel genes, the group has interest in searching new drugs and their molecular targets, which is aimed to translate the research to new therapeutics. The ongoing projects include Ca2+signalling and oxidative stress; molecular aspect of cardiovascular risk factors; development of new channel blockers; and cell signalling in proliferation and apoptosis.
Techniques used in the lab
Molecular technologies including gene cloning, transfection, RT-PCR, real-time PCR, ELISA, Western blotting, siRNA techniques, site-mutagenesis, cell proliferation, migration and apoptosis, immunocytochemistry, immunoprecipitation, flowcytometry; Electrophysiological skills inlcude whole-cell patch and excised membrane patch, single channel recordings; Calcium imaging and fluorescence resonance energy transfer (FRET); and biotechnology including antibody design, generation, conjugation and purification and protein engineering.
Full Publication List:
Li P, Rubaiy HN, Chen GL, Hallett T, Zaibi N, Zeng B, Saurabh R, Xu SZ. Mibefradil, a T-type Ca2+ channel blocker also blocks Orai channels by action at the extracellular surface. Br J Pharmacol. 2019 Jul 4. doi: 10.1111/bph.14788
Farmer LK, Rollason R, Whitcomb DJ, Ni L, Goodliff A, Lay AC, Birnbaumer L, Heesom KJ, Xu SZ, Saleem MA, Welsh GI. TRPC6 Binds to and Activates Calpain, Independent of Its Channel Activity, and Regulates Podocyte Cytoskeleton, Cell Adhesion, and Motility. Journal of the American Society of Nephrology 2019 DOI: 10.1681/ASN.2018070729.
Zeng, B. Chen, G.L., Garcia-Vaz, E., Bhandari, S., Daskoulidou,N., Berglund, L.M., Jiang, H., Hallett, T., Zhou, L.P., Huang, L., Xu, Z.H., Nair, V., Nelson, R.G., Ju, W., Kretzler, M., Atkin, S.L., Gomez, M.F., Xu, S.Z. ORAI channels are critical for receptor-mediated endocytosis of albumin. Nature Communications 2017; 8: 1920
Daskoulidou, N., Zeng, B., Berglund, L.M., Jiang, H., Chen, G.L., Kotova, O., Bhandari, S., Ayoola, J., Griffin, S., Atkin, S.L., Gomez, M.F., Xu, S.Z. High Glucose Enhances Store-Operated Calcium Entry by Upregulating ORAI/STIM via Calcineurin-NFAT Signalling. J Mol Med 2015; 93(5): 511-521.
Zeng, B, Chen, GL, Daskoulidou, N, Xu, SZ. The ryanodine receptor agonist 4-chloro-3-ethylphenol blocks ORAI store-operated channels. Br J Pharmacol 2014; 171: 1250-1259.
Xu, S.Z., Sukumar, P., Zeng, F., Li, J., Jairaman, A., English, A., Naylor, J., Ciurtin, C., Majeed, Y., Milligan, C.J., Bahnasi, Y.M., Al-Shawaf, E., Porter,K.E., Jiang, L.H., Emery, P., Sivaprasadarao, A. & Beech, D.J. 2008. TRPC channel activation by extracellular thioredoxin. Nature, 451, 69-72.
Xu, S. Z., Zeng, F., Lei, M., Li, J., Gao, B., Xiong, C., Sivaprasadarao, A., & Beech, D. J. 2005. Generation of functional ion-channel tools by E3 targeting. Nature Biotechnology, 23(10): 1289-1293.
Xu, S. Z., Muraki, K., Zeng, F., Li, J., Sukumar, P., Shah, S., Dedman, A. M., Flemming, P. K., Naylor, J., Cheong, A., Bateson, A. N., Porter, K. E., Munsch, C. M., & Beech, D. J. 2006. A sphingosine-1-phosphate activated calcium channel controlling vascular smooth muscle cell motility.Circulation Research, 98:1381-9. (see Editorials in Circulation Research 2006;98;1347-1348
Kumar, B.*, Dreja, K.*, Shah, S.*, Cheong, A.*, Xu, S. Z.*, Sukumar, P., Forte, A., Cipollaro, M., McHugh, D., Munsch, C. M., Porter, K. E., Kingston, P. A., Heagerty, A. M., Bergdahl, A., Hultgardh-Nilsson, A., Gomez, M. F., Hellstrand, P., & Beech, D. J. 2005. Up-regulated TRPC1 channel in vascular injury in vivo and its role in human neointimal hyperplasia. Circulation Research, 98(4): 557-63.
Xu, S. Z., & Beech, D. J. 2001. TrpC1 is a membrane-spanning subunit of store-operated Ca2+ channels in native vascular smooth muscle cells.Circulation Research, 88(1): 84-87.