Education

Biography

He is investigating the molecular mechanisms and therapeutic interventions associated with glycolytic high energy phosphoenolpyruvate (PEP)- and focal adhesion kinase (FAK)-driven tumorigenicity. His work focuses on: 1) PEP-phosphohistidine signaling modulation of primitive proliferation and survival,2) pro-glycolytic function of focal adhesion kinase (FAK), 3) initiation of tumor apoptosis by targeting FAK and mTOR, 4) a new serine phosphorylation site (S214) on FAK for FAK-IGF-1R interaction, 5) FAK-pyruvate kinase M2 (PKM2) signaling in malignancies, and 6) anticancer small molecules targeting oncogenes and enzymes that promote excessive glucose consumption in order to cut off fuel supplies and prevent tumor growth.

Research Interest

• Glucose control of primitive proliferation and survival
• Phosphohistidine signaling in tumor cells
• Focal adhesion kinase-pyruvate kinase M2 interaction
• Glucose oncometabolism
• Anticancer small molecules targeting reprogramed metabolism

Professional Activities:

Scientific Activities:

• Committee Member of the International Society at Sutton Bonington, England, U.K. 1991-1992
• Awarded the Technical Co-operation Scholarship by the British Council, England, U.K. 1990-1993
• Awarded the Belper Postgraduate Scholarship by the University of Nottingham, England, 1992
• Member of the Biochemical Society in England. 1991-present
• Member of the Society for Free Radical Biology and Medicine, 1998-present
• Member of the American Society for Cell Biology, 2005-present
• Reviewed grants for American Heart Association (the Region I Basic Cell 4 committee 2009; the Lung 2 committee, 2010, 2011, 2012) and National Science Foundation of Austria
• Scientific Council Member of American Heart Association, 2001-present
• Patents “DNA encoding a pectin esterase, cells and plants derived therefrom”. USA #: 5, 910, 632; UK # 9403406.3; Canada; PCT international application No. PCT/GB95/00367
• Adjunct professor and member of the Academic Committee/the Cell Biology textbook editorial board at the Institute of Cell Biology/Department of Cell Biology and Histology & Embryology, Zhejiang University School of Medicine, China. 2004-present
• Member of Board of Directors of the American Journal of Traditional Chinese Veterinary Medicine. 2006-present
• Member of the Research Task Force of the Pulmonary Division of Department of Medicine, the University of Florida, 2006-2011
• Editorial Board Member of the International Journal of Clinical and Experimental Medicine, 2009-present
• Member of the Subcommittee for Research Safety NF/SG VHS, 2009-2011
• Member of the Research Facility and Space Utilization Subcommittee, 2009-2011
• Member of the Chi Institute of Chinese Medicine, IACUC, 2010-present

Publications

Books:

• Patel, J. M., Zhang, J., Li, Y. D. and Block, E. R. (2003) Calreticulin Regulation of Lung Endothelial NOS Activity in Calreticulin in Health and Disease. Pages 205-216. (Eds. P. Eggleton and M. Mitchalak) Landes Bioscience. Kluwer Academic/ Plenum Publishers, 233 Spring street, New York, NY, USA, 10013.
• Zhang, J. (2005) Stem Cell Biology (chapter 17) in Medical Cell Biology (in Chinese). ISBN 7-308-04376-2. Pages 323-336. Ed. Jicheng Li. Zhejiang University Academic Press, 38 Zheda Road, Zhejiang Province, PRC, 310028. http://www.zjupress.com.
• Zhang, J. (2005) Review and Practice for Medical Cell Biology (in Chinese). ISBN 7-308-04376-5. Pages 161-171. Ed. Jicheng Li. Zhejiang University Academic Press, 38 Zheda Road, Zhejiang Province, PRC, 310028. http://www.zjupress.com.

Journals:

1. Zhang, J., Patel, J. M., Li, Y. D., and Block, E. R. (1996) Reductase domain cysteines 1048 and 1114 are critical for catalytic activity of human endothelial cell nitric oxide synthase as probed by site-directed mutagenesis. Biochem. and Biophysi. Res. Comm. 226: 293-300.
2. Patel, J. M., Zhang, J., and Block, E. R. (1996) Nitric oxide-induced inhibition of lung endothelial cell nitric oxide synthase via interaction with allosteric thiols: role of thioredoxin in regulation of catalytic activity. Am. J. Respir. Cell Mol. Biol. 15: 410-419.
3. Zhang, J., Patel, J. M., Li, Y. D., and Block, E. R. (1997) Proinflammatory cytokines down regulate gene expression and activity of constitutive nitric oxide synthase in pig pulmonary artery endothelial cells (PAEC). R. C. in Molecular Pathology and Pharmacology, 96:71-87.
4. Zhang, J., Patel, J. M., and Block, E. R. (1997) Molecular cloning, characterization and expression of a nitric oxide synthase from porcine pulmonary artery endothelial cells. Compar. Biochem. and Physiol. 116b: 485-491.
5. Li, Y. D., Patel, J. M., Zhang, J. and Block, E. R. (1997) Overexpression of plasma membrane annexin II in NO2-induced pulmonary artery endothelial cells. Free Radical Biol. & Medicine, 23:120-126.
6. Zhang, J., Patel, J. M., and Block, E. R. (1998) Thioredoxin over-expression prevents NO-induced reduction of NO synthase activity in lung endothelial cells. Am. J. Physiol. 275: L288-293.
7. Zhang, J., Patel, J. M., and Block, E. R. (1998) Hypoxia causes specific upregulation of calpain activity and gene expression in pulmonary artery endothelial cells. Am. J. Physiol. 275: L461-468.
8. Zhang, J., Patel, J. M., and Block, E. R. (1999) Nitric oxide-induced modulation of thioredoxin gene expression is regulated by NF-kB pathway in lung endothelial cells. Am. J. Physiol. (Lung Cell Mol. Physiol.) 277: L787-L793.
9. Patel, J. M., Y. D. Li, Zhang, J., C. H. Gelband, M. K. Raizada, and Block, E. R. (1999) Increased expression of calreticulin is linked to angiotensin IV-mediated activation of lung endothelium NOS. Am. J. Physiol. (Lung Cell Mol. Physol.) 277: L794-L801.
10. Zhang, J., Patel, J. M., and Block, E. R. (1999) Nitric oxide increases gene transcripts in lung artery endothelial cells. Am. J. Respir. Critical Care Med., 159: A287.
11. Griffiths, A., Prestage S., Linforth, R., Zhang, J., Taylor, A., and Grierson, D. (1999) Fruit specific lipoxygenase suppression in antisense-transgenic tomatoes. Postharvest Biology and Technology. 17: 163-173.
12. Zhang, J. L., Patel, J. M., and Block, E. R. (2000) Senescent Apoptosis of Lung Endothelial Cells is Associated with Deficiency of Mitochondrial Cytochrome c Oxidase". Am. J. Crt. Care Med. 161: A513.
13. Gerencser, G. A., and Zhang, J. (2001) Cl-ATPases: Novel primary active transporters in biology. J. Exp. Zoolog. 289: 215-223.
14. Gerencser, G. A., and Zhang, J. (2001) Phosphorylation of chloride-ATPase reconstituted from Aplysia Gut. J. Exp. Zoolog. 289: 472-475.
15. Gerencser, G. A., and Zhang, J. (2001) Inhibition of a chloride-translocating P-type ATPase in Aplysia Gut. Zoolog. Sci. 18: 17-19.
16. Gerencser, G. A., and Zhang, J. (2001) The Aplysia Californica Cl pump is a P-type ATPase: evidence through inhibition studies. Can. J. Physiol. Pharmacol. 79: 367-370.
17. Gerencser, G. A., Ahearn, G. A., Zhang, J., and Cattey, M. A. (2001) Sulfate transport mechanisms in epithelial systems. J. Exp. Zoolog. 289: 245-253.
18. Gerencser, G. A., and Zhang, J. (2001) Cl-ATPases: biological active transporters. Compar. Biochem. and Physiol. 130: 511-519.
19. Zhang, J., Block, E. R. and Patel, J. M. (2002) Enhanced apoptosis in prolonged cultures of senescent porcine pulmonary artery endothelial cells. Mech Ageing Dev. 123: 613-625.
20. Zhang, J., Xia, S., Block, E. R. and Patel, J. M. (2002) NO upregulation of a cyclic nucleotide-gated channel contributes to sustained elevation of intracellular calcium in lung artery endothelial cells. Am J Physiol Cell Physiol 283: C1080-C1089.
21. Zhang, J., Block, E. R. and Patel, J. M. (2002) Downregulation of mitochondrial cytochrome c oxidase in senescent vascular endothelial cells. Mech Ageing Dev. 123:1363-1374.
22. Gerencser, G. A., Levin, R and Zhang, J. (2002) Sodium-phosphate symport by Aplysia californica gut. Zoolog. Sci. 19(2): 163-166.
23. Gerencser, G. A., Loo., S. Y., Cornette, K. M. and Zhang, J. (2002) Energetics of potassium ion transport in Aplysia gut. Zoolog. Sci. 19(6): 629-632.
24. Gerencser, G. A., Levin, R. and Zhang, J. (2002). Phosphate absorption by Aplysia californica gut: thyroid hormone stimulation. Can. J. Physiol. Pharmacol. 80(6): 604-607.
25. Gerencser, G. A., Levin, R. and Zhang, J. (2002). Sulfate absorption in Aplysia californica gut: thyroid hormone stimulation. Can. J. Zoolog. 80(6): 964-966.
26. Gerencser, G. A. and Zhang, J. (2002). Chloride-ATPase dephosphorylation in Aplysia gut. J. Exp. Zoolog. 293(1): 89-93.
27. Gerencser, G. A., Zhang, J. and Levin, R. (2002). Sulfate absorption in Aplysia californica gut: glucocorticoid inhibition. Can. J. Zoolog. 80: 2037-2040.
28. Gerencser, G. A., Cornette, K. M. and Zhang, J. (2002). Thyroid-hormone-induced phosphate absorption in Aplysia californica gut is mediated through protein synthesis. Can. J. Physiol. Pharmacol. 80: 1195-1198.
29. Kahlos, K., Zhang, J., Block, E. R. and Patel, J. M. (2003) Thioredoxin restores nitric oxide-induced inhibition of protein kinase C activity in lung endothelial cells. Molecular and Cellular Biochemistry. Molecular and Cellular Biochemistry. 254: 47-54.
30. Xin, M. G., Zhang, J., Block, E. R. and Patel, J. M. (2003) Enhanced oxidative stress in porcine pulmonary artery endothelial cells is associated with deficiency of mitochondrial cytochrome c oxidase. Mech Ageing Dev. 124:911-919.
31. Gerencser, G. A. and Zhang J. (2003). Existence and nature of the chloride pump. Biochim Biophys Acta 1618(2): 133-9.
32. Gerencser, G. A. and Zhang, J. (2003). Chloride ATPase pumps in nature: do they exist? Biol Rev Camb Philos Soc 78(2): 197-218.
33. Gerencser, G. A., Loo, S. Y., Robbuns, F.W. and Zhang, J. (2003) Phosphate absorption in Aplysia californica gut: glucocorticoid inhibition. Can. J. Physiol. Pharmacol. 81(4): 409-12.
34. Gerencser, G. A., Loo, S. Y. and Zhang, J. (2003) Thyroid hormone-induced sulfate absorption in Aplysia californica gut is mediated by protein synthesis. Can. J. Physiol. Pharmacol. 81(4): 405-8.
35. Gerencser, G. A., Robbins, F., Zhang, J. and Ahearn, G. A. (2004). Electrogenic proton-regulated oxalate/chloride exchange by lobster hepatopancreatic brush-border membrane vesicles. J. Exp. Biol. 207 (Pt 4): 571-578.
36. Hu, H., Xin, M., Belayev, L. L., Zhang, J., Block, E.R. and Patel, J. M. (2004) Autoinhibitory domain fragment of endothelial NOS enhances pulmonary artery vasorelaxation by the NO/ cGMP pathway. Am J Physiol Lung Cell Mol Physiol 286: L1066-L1074.
37. Li, L., Zhang, J., Block, E. R. and Patel, J. M. (2004) Nitric oxide-modulated marker gene expression of signal transduction pathways in lung endothelial cells. Nitric Oxide 11(4): 290-297.
38. Zhang, J., Jin, B., Li, L., Block, E. R. and Patel, J. M. (2005) NO-induced persistent inhibition and nitrosylation of active site cysteines of mitochondrial cytochrome c oxidase in lung endothelial cells. Am J Physiol Cell Physiol. 288(4): C840-9.
39. Lu, J. H., Zhang, J., Block, E. R. and Patel, J. M. (2005) Angiotensin IV enhances phosphorylation state of eIF-4E and 4E-BP1 proteins in lung endothelial cells. Molecular and Cellular Biochemistry. 275: 181-188.
40. Li, L., Zhang, J., Block, E. R. and Patel, J. M. (2007) Nitric oxide upregulation of caspase-8 mRNA expression in lung endothelial cells: role of JAK2/STAT-1 signaling. Molecular and Cellular Biochemistry. 305 (1-2): 71-77.
41. Aldonyte, R., Hutchinson, E. T., Jin, B., Brantly, M., Block, E. R., Patel, J., and Zhang, J. (2008) Endothelial alpha-1-antitrypsin attenuates cigarette smoke induced apoptosis. COPD. 5 (3):153-162.
42. Aldonyte, R., Pivoriunas, A., Zhang, J. and Brantly, M. (2008) Human neutrophil peptide 2 impairs wound-induced migration of cultured pulmonary endothelial cells. Acta Medica Lithuanica. 15 (4): 206-210.
43. Aldonyte, R., Brantly, M., Block, E., Patel, J., and Zhang, J. (2009) Nuclear localization of active MMP-2 in cigarette smoke-exposed apoptotic endothelial cells. Experimental Lung Research. 35(1): 59-75.
44. Zhang, J., Juedes, N., Narayan, V. and Patel, J. (2009) Hypoxic upregulation of preproendothelin-1 gene expression is associated with protein tyrosine kinase-PI3K signaling in cultured pulmonary vascular endothelial cells. The International Journal of Clinical and Experimental Medicine. 2(1):87-94.
45. Zhang, J., Juedes, N., Narayan, V., Yue, B., Rockwood, A., Palma, N. and Patel, J. (2010) A cellular model to mimic exhaled cigarette smoke-induced lung microvascular endothelial cell injury and death. The International Journal of Clinical and Experimental Medicine. 3(3): 223-232.
46. Zhang, J. and Patel, J. (2010) Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases. The International Journal of Clinical and Experimental Medicine. 3(3): 233–244.
47. Hutchinson, T., Zhang, J. Xia, S., Kuchibhotla, S., Block, E. and Patel, J. (2012) Enhanced phosphorylation of caveolar PKC-α limits peptide internalization in lung endothelial cells. Molecular and Cellular Biochemistry. 360(1-2):309-20. Epub 2011 Sep 24.
48. Zhang, J., Palma, N., Harrison, J. K., Mubarak, K., Carrie, R., Alnuaimat, H., and Patel, J. (2012) Hypoxia-induced endothelial CX3CL1 triggers lung smooth muscle cell proliferation. Am. J. Physiol. (Lung Cell Mol. Physiol.) 303:L912-L922, 2012. First published 21 September 2012.
49. Ucar, D., Magis, A., He, D., Lawrence, N., Sebti, S. Kurenova, E., Zajac-Kaye, M., Zhang, J., and Hochwald, S. (2013) Inhibiting the interaction of receptor proteins with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo. Anticancer Agents in Medicinal Chemistry. 13(4):595-602. Epub 2012 Dec 14.
50. Zhang, J., and Hochwald, S (2013) Plasma adiponectin: a possible link of fat metabolism and pancreatic cancer risk. Journal of National Cancer Institute. Journal of National Cancer Institute. 105(2): 95-103. Epub 2012 Dec 14.
51. Zhang, J., Zajac-Kaye, M., Francois, F., and Hochwald, S (2013) Current understanding of the molecular biology of pancreatic neuroendocrine tumors (PNETs). Journal of National Cancer Institute. 105(14):1005-17. Epub 2013 Jul 9.
52. Zhang J., Hochwald SN. (2013) Targeting receptor tyrosine kinases in solid Tumors. Surgical Oncology Clinics of North America. 22(4):685-703. doi: 10.1016/j.soc.2013.06.010. Epub 2013 Jul 30.
53. Zhang J., Hochwald SN. (2014) The role of FAK in tumor metabolism and therapy. Pharmacology and Therapeutics. 142(2):154-163. doi: 10.1016/j.pharmthera.2013.12.003. Epub 2013 Dec 9.
54. Zhang J., He D., Zajac-Kaye M., and Hochwald SN. (2014) A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells. Cell Cycle. 142(2):154-63.
55. Zhang J., Gao Q., Zhou Y., Dier U., Hempel N., Hochwald SN. (2015) Focal adhesion kinase-promoted tumor glucose metabolism is associated with a shift of mitochondrial respiration to glycolysis. Oncogene.PMID: 26119934.
56. Oyasiji T., Zhang J., Kuvshinoff B., Iyer R., Hochwald SN. (2015) Molecular Targets in Biliary Carcinogenesis and Implications for Therapy. The oncologist. 20(7):742-751. PMID: 26025932.
57. Guo L., Tian S., Chen Y., Mao Y., Cui S., Hu A., Zhang J., Xia SL., Su Y., Du J., Block ER., Wang XL., Cui Z. (2015) CAT-1 as a novel CAM stabilizes endothelial integrity and mediates the protective actions of l-Arg via a NO-independent mechanism. J Mol Cell Cardiol. 87:180-91. PMID: 26283571. doi: 10.1016/j.yjmcc.2015.08.011. Epub 2015 Aug 15.