Dr Sam Xu

Reader in Diabetes, Endocrinology & Metabolism

Sam is a reader in Diabetes, Endocrinology and Metabolism. His research is in the molecular biology, ion channel and receptor pharmacology, disease mechanism and drug discovery, especially the TRP and store-operated channels in cardiovascular diseases and diabetes. Sam is tutor for HYMS SSIP. 

Dr Shang-Zhong (Sam) Xu is a reader in the Centre for Cardiovascular and Metabolic Research. He obtained his BM in clinical medicine from Shandong Medical University (1986), MSc in Pharmacology from Shanghai Medical University (1989, Shanghai) and MD in Cardiology (1996, Shanghai). He worked as a resident physician, specialist and then associate professor and consultant cardiologist (1989-1998). He was enthusiastic for medical research and investigated ATP-sensitive K channels in Leeds as a visiting scholar. He moved to Leeds for PhD study (PhD, 2001, Leeds) and postdoctoral research fellow (2001-2005). He studied TRP and store-operated channels in cardiovascular diseases, working in Prof. DJ Beech's laboratory (1998-2005). Sam joined the Postgraduate Medical Institute and Hull York Medical School as a Lecturer in 2005 and became Senior Lecturer, and then Reader in HYMS. 

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. 


PhD/MD/MSc projects


Please contact me if you are planning to apply PhD, MD and MSc studies in the laboratory in the field of vascular disease, diabetes and obesity.    

Selected publications


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.

Zeng B,  Yuan C, Yang X, Atkin SL, Xu SZ. TRPC Channels and Their Splice Variants are Essential for Promoting Human Ovarian Cancer Cell Proliferation and Tumorigenesis. Current Cancer Drug Targets 2013:13(1):103-16.

 Jiang HN, Zeng B, Zhang Y, Daskoulidou N, Fan H, Qu JM & Xu SZ. Involvement of TRPC channels in lung cancer cell differentiation and the correlation analysis in human non-small cell lung cancer. PLOS One 2013: 8(6):e67637.

Chen GL, Zeng B, Eastmond S, Elsenussi SE, Boa AN, Xu SZ. Pharmacological comparison of novel synthetic fenamate analogues with econazole and 2-APB on the inhibition of TRPM2 channels. Br J Pharmacol 2012:167(6):1232-43.

Zeng B, Chen GL, Xu SZ. 2012. Store-independent pathways for cytosolic STIM1 clustering in the regulation of store operated Ca2+ influx.Biochem Pharmacol  84(8):1024-35.

Jiang H, Zeng B, Chen GL, Bot D, Eastmond S, Elsenussi SE, Atkin SL, Boa AN, Xu SZ.  2012.  Effect of non-steroidal anti-inflammatory drugs and new fenamate analogues on TRPC4 and TRPC5 channels. Biochem Pharmacol 83:923-931

Xu SZ, Zeng B, Daskoulidou N, Chen, G, Atkin SL, Lukhele B. 2012. Activation of TRPC cationic channels by mercurial compounds confers the cytotoxicity of mercury exposure. Toxicological Sciences, 125:56-68.

Xu SZ. 2010. Assessing TRPC Channel Function Using Pore-blocking Antibodies. In: Michael XI Zhu (ed.), TRP Channels. Methods in Signal Transduction Series.  CRC press, Taylor & Francis Group.

Xu, S.Z., Zhong, W., Ghavideldarestani, M., Saurabh, R., Lindow, S.W., Atkin, S.L. 2009. Multiple mechanisms of soy isoflavones against oxidative stress induced endothelium injury. Free Radical Biology & Medicine, 47:167-75.

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., Zhong, W., Watson, N.M., E. Dickerson, Wake, J., Lindow, S., Newton, C., & Atkin, S. L. 2008. Upregulation of Bcl-2 is a novel mechanism for fluvastatin against oxidative damages in human vascular endothelial cells. Journal of Thrombosis and Haemostasis 6:692-700.

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.

Yoo, S., Dobrzynski, H., Fedorov, V.V., Xu, S.Z., Yamanushi, T.T., Jones, S.A., Yamamoto, M., Nikolski, V.P., Efimov, I.R., Boyett, M.R. 2006. Localization of Na+ channel isoforms at the atrioventricular junction and atrioventricular node in the rat. Circulation, 114(13):1360-71.

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

Bergdahl, A., Gomez, M. F., Dreja, K., Xu, S. Z., Adner, M., Beech, D. J., Broman, J., Hellstrand, P., & Sward, K. 2003. Cholesterol depletion impairs vascular reactivity to endothelin-1 by reducing store-operated Ca2+ entry dependent on TRPC1. Circulation Research, 93(9): 839-847.

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.

Xu SZ, Zhou W, Mao XD, Xu J, Xu LP & Ren JY. (2001). Reference data and predictive diagnostic models for calcaneus bone mineral density measured with single-energy X-ray absorptiometry in 7428 Chinese. Osteoporosis International 12, 755-762.



(Selected oldies, 1992-2000)

Xu, S. Z., Mao, X. D., & Zhou, W. 2000. Efficacy of alendronate in treating osteoporosis in old women. New Drug and Clinical Remedies, 19: 289-291.

Xu, S. Z., Huang, W. M., & Ren, J. Y. 1997. The new model of age-dependent changes in bone mineral density. Growth Development and Aging, 61(1): 19-26.

Xu, S. Z., Huang, W. M., Ren, J. Y., Zhang, R. F., & Zhu, H. M. 1997. A controlled double-blind clinical trial of alfacalcidol in treating senile osteoporosis. New Drugs and Clinical Remedies, 15: 177-178.

Xu, S. Z., Zhu, X. Y., & Yan, S. Q. 1997. Electrophysiological effects of gallanilide on cardiac ventricular and Purkinje fibers. Drug Development Research, 40(1): 94-98.

Xu, S.Z., Huang, W.M. & Ren, J.Y. 1997. Clinical observation of the heart rate variability in 118 healthy volunteers. Chinese Journal of Pacing and Electrophysiology 11, 126-127.

Xu, S.Z., Huang, W.M. Computer simulation of the relationship between action potential and ionic currents in ventricular myocardium cell. Japanese Heart Journal 35, 263-264 (1994).

Xu, S. Z., Chen, Y., & Hong, Y. C. 1993. An optimum computer program for evaluating dissolution rate of solid preparations. Journal of Chinese Pharmaceutical Industries 24(3): 122-124.

Huang, W. M., Xu, S. Z. 1992. A study of the antiarrhythmic mechanism of berberine on delayed activation potassium current by voltage clamp. Chinese Journal of Cardiology, 20(5): 310-312, 325.


 

 


 

Hull York Medical School


SSIP Lead (Phase 1, CCMR)

Physiology Society (member, 1999- )

British Endocrinology Society (member, 2005-)

International Society of Electrocardiology (member, 1994-)

Biophysics Society, USA  (member, 2000-2012)

Academic editor, PLoS One


Lund University

University of Bristol 

Fudan University

Contact details
sam.xu@hyms.ac.uk
01482 465372

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