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研究领域

Hepatocyte polarisation Hepatocytes are the most abundant cells in the liver, and when polarised have apical and basolateral membranes separated by tight junctions. The formation and maintenance of a polarised epithelium is multifaceted, requiring specific cell-cell adhesion molecules, cytoskeletal factors, and intracellular trafficking components. Loss of polarity is likely to be a common denominator in liver failure associated with drug toxicity, alcoholism, cancer and viral infections. Understanding how hepatocyte repolarisation occurs in response to these conditions has important implications for treating liver disease and facilitating regeneration. Dr Fu uses a combination of cell biology, biochemical and imaging techniques to investigate the mechanism of hepatocyte polarisation. Potential projects: How does energy metabolism (AMPK and mitochondrial functions) regulate hepatocyte polarisation components (tight junction, cytoskeleton and apical trafficking)? How drugs and/or pathogens affect hepatocyte polarisation and cause liver injury. ABC transporter trafficking. ATP-binding cassette (ABC) transporters are transmembrane proteins and important for many physiological functions (drug excretion, bile secretion and cholesterol transport). and pathological conditions (multidrug resistance in cancer chemotherapy). Dr Fu’s research investigates the cellular regulatory pathways for ABC transporter trafficking/recycling in polarised cells or cancer cells, focusing especially on the role of small GTPases and cytoskeletal proteins.

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Khanal, D., Kondyurin, A., Hau, H., Knowles, J., Levinson, O., Ramzan, I., Fu, D., Marcott, C., Chrzanowski, W. (2016). Biospectroscopy of Nanodiamond-Induced Alterations in Conformation of Intra- and Extracellular Proteins: A Nanoscale IR Study. Analytical Chemistry, 88(15), 7530-7538. [More Information] Khanal, D., Dillon, E., Hau, H., Fu, D., Ramzan, I., Chrzanowski, W. (2015). Lorentz contact resonance spectroscopy for nanoscale characterisation of structural and mechanical properties of biological, dental and pharmaceutical materials. Journal of Materials Science: Materials in Medicine, 26(12), 1-10. [More Information] Homolya, L., Fu, D., Sengupta, P., Jarnik, M., Gillet, J., Vitale-Cross, L., Gutkind, J., Lippincott-Schwartz, J., Arias, I. (2014). LKB1/AMPK and PKA Control ABCB11 Trafficking and Polarization in Hepatocytes. PloS One, 9(3), e91921. [More Information] Fu, D., Mitra, K., Sengupta, P., Jarnik, M., Lippincott-Schwartz, J., Arias, I. (2013). Coordinated elevation of mitochondrial oxidative phosphorylation and autophagy help drive hepatocyte polarization. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 110(18), 7288-7293. [More Information] Fu, D., Lippincott-Schwartz, J., Arias, I. (2013). Increased mitochondrial fusion and autophagy help isolated hepatocytes repolarize in collagen sandwich cultures. Autophagy, 9(12), 2154-2155. [More Information] Fu, D. (2013). Where is it and how does it get there - intracellular localization and traffic of P-glycoprotein. Frontiers in Oncology, 3, 1-5. [More Information] Fu, D., Arias, I. (2012). Intracellular trafficking of P-glycoprotein. The International Journal of Biochemistry and Cell Biology, 44(3), 461-464. [More Information] Fu, D., Wakabayashi, Y., Lippincott-Schwartz, J., Arias, I. (2011). Bile acid stimulates hepatocyte polarization through a cAMP-Epac-MEK-LKB1-AMPK pathway. Proceedings of the National Academy of Sciences of the United States of America (PNAS), 108(4), 1403-1408. [More Information] Fu, D., Lippincott-Schwartz, J., Arias, I. (2011). Cellular mechanism of bile acid-accelerated hepatocyte polarity. Small GTPases, 2(6), 314-317. [More Information] Baranova, I., Bocharov, A., Vishnyakova, T., Kurlander, R., Chen, Z., Fu, D., Arias, I., Csako, G., Patterson, A., Eggerman, T. (2010). CD36 is a novel serum amyloid A (SAA) receptor mediating SAA binding and SAA-induced signaling in human and rodent cells. Journal of Biological Chemistry, 285(11), 8492-8506. [More Information] Fu, D., Wakabayashi, Y., Ido, Y., Lippincott-Schwartz, J., Arias, I. (2010). Regulation of bile canalicular network formation and maintenance by AMP-activated protein kinase and LKB1. Journal of Cell Science, 123(19), 3294-3302. [More Information] Kovacevic, Z., Fu, D., Richardson, D. (2008). The iron-regulated metastasis suppressor, Ndrg-1: Identification of novel molecular targets. BBA: Biochimica et Biophysica Acta - Molecular Cell Research, 1783 (10), 1981-1992. [More Information] Fu, D., Roufogalis, B. (2007). Actin Disruption Inhibits Endosomal Traffic of P-glycoprotein-EGFP and Resistance to Daunorubicin Accumulation. American Journal of Physiology: Cell Physiology, 292(4), C1543-C1552. [More Information] Fu, D., Richardson, D. (2007). Iron chelation and regulation of the cell cycle: 2 mechanisms of posttranscriptional regulation of the universal cyclin-dependent kinase inhibitor p21CIP1/WAF1 by iron depletion. Blood, 110(2), 752-761. [More Information] Nurtjahja-Tjendraputra, E., Fu, D., Phang, J., Richardson, D. (2007). Iron chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression. Blood, 109(9), 4045-4054. Fu, D., van Dam, E., Brymora, A., Duggin, I., Robinson, P., Roufogalis, B. (2007). The small GTPases Rab5 and RalA regulate intracellular traffic of P-glycoprotein. BBA: Biochimica et Biophysica Acta - Molecular Cell Research, 1773 (7), 1062-1072. [More Information] Nurtjahja-Tjendraputra, E., Fu, D., Phang, J., Richardson, D. (2006). Iron Chelation regulates cyclin D1 expression via the proteasome: a link to iron deficiency-mediated growth suppression. Blood, 109(9), 4045-4054. [More Information] Fu, D., Bebawy, M., Kable, E., Roufogalis, B. (2004). Dynamic And Intracellular Trafficking Of P-Glycoprotein-EGFP Fusion Protein: Implications In Multidrug Resistance In Cancer. International Journal of Cancer, 109(2), 174-181. [More Information] Sun, L., Liu, X., Qiu, L., Wang, J., Liu, M., Fu, D., Luo, Q. (2001). Administration of plasmid DNA expressing human interleukin-6 significantly improves thrombocytopoiesis in irradiated mice. Annals of Hematology, 80(10), 567-572. [More Information]

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