Meech, Robyn - Flinders University - Department of Clinical Pharmacology

研究领域

1.Homeobox genes in development and stem cell function: Homeobox proteins control cell-type specification and tissue patterning in embryogenesis and also have roles in adult stem cell mediated-regenerative processes. The Barx homeobox family are involved in survival, proliferation and differentiation of muscle, skin and possibly cancer stem cells. Studies of Barx2 in muscle development, repair and aging are currently funded by an NIH R01 grant and involves collaborations at the Scripps Research Institute in San Diego. 2.Wnt effector pathways in stem cells: The Wnt signaling pathway plays a major role in development and in adult stem cell function; its deregulation is also implicated in both aging and cancer. We are interested in factors that lend specificity to the transcriptional effector complex (b-catenin/TCF) that regulates gene expression downstream of the canonical wnt signalling pathway. Our recent work shows that Barx genes are "specificity regulators" that may control the transcriptional effects of wnt signals in muscle and other tissues. 3.Cancer stem cells: It is currently believed that dysregulated tissue specific stem cells can initiate tumour formation and that within any tumour, there is a subset of cells that retain stem cell properties and can give rise to new tumours if they escape and are disseminated to distal sites (metastasis). Many cancer cell lines also appear to harbor cells with such stem cell characteristics. One characteristic of stem cells is that they are slow-dividing or even quiescent whilst in their niche. In tumours, this slow-dividing property may allow cancer stem cells to escape the effects of anti-cancer drugs that target rapid cell proliferation. We are working on molecular approaches to label and isolate breast cancer stem cells and characterize wnt pathways, homeobox proteins (Barx) and estrogen signalling. This work is supported by a FMC foundation grant.

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Hu, D.G., Selth, L., Tarulli, G.A., Meech, R., Chanawong, A., Wijayakumara, D.D., et al. (2016). Androgen and estrogen receptors in breast cancer co-regulate human UDP-glucuronosyltransferases 2B15 and 2B17. Cancer Research, Hu, D.G., Mackenzie, P.I., McKinnon, R.A. and Meech, R. (2016). Genetic polymorphisms of human UDP-glucuronosyltransferases (UGT) genes and cancer risk. Drug Metabolism Reviews, 48(1) Hulin, J.A., Nguyen, T.D., Cui, S., Marri, S., Yu, R.T., Downes, M.R., et al. (2016). Barx2 and Pax7 regulate Axin2 expression in myoblasts by interaction with ?-catenin and chromatin remodelling. Stem Cells, [10.1002/stem.2396] [Scopus] Wijayakumara, D.D., Hu, D.G., Meech, R., McKinnon, R.A. and Mackenzie, P.I. (2015). Regulation of human UGT2B15 and UGT2B17 by miR-376c in prostate cancer cell lines. Journal of Pharmacology and Experimental Therapeutics, 354(3) pp. 417-425. [Scopus] Nair, P.C., Meech, R., Mackenzie, P.I., McKinnon, R.A. and Miners, J.O. (2015). Insights into the UDP-sugar selectivities of human UDP-glycosyltransferases (UGT): a molecular modeling perspective. Drug Metabolism Reviews, 47(3) pp. 335-345. [10.3109/03602532.2015.1071835] [Scopus] Hu, D.G., Mackenzie, P., Lu, L., Meech, R. and McKinnon, R.A. (2015). Induction of human UDP-glucuronosyltransferase 2B7 gene expression by cytotoxic anticancer drugs in liver cancer HepG2 cells. Drug Metabolism and Disposition, 43(5) pp. 660-668. [10.1124/dmd.114.062380] [Scopus] Chanawong, A., Hu, D.G., Meech, R., Mackenzie, P. and McKinnon, R.A. (2015). Induction of UDP-glucuronoslytransferase 2B15 gene expression by the major active metabolites of tamoxifen, 4-hydroxytamoxifen and endoxifen, in breast cancer cells. Drug Metabolism and Disposition, 43 pp. 889-897. [10.1124/dmd.114.062935] [Scopus] Barnawi, J., Tran, H.B., Jersmann, H.P., Pitson, S., Roscioli, E., Hodge, G., et al. (2015). Potential Link between the Sphingosine-1-Phosphate (S1P) System and Defective Alveolar Macrophage Phagocytic Function in Chronic Obstructive Pulmonary Disease (COPD) PLoS One, 10(10) pp. Art: e0122771. [10.1371/journal.pone.0122771] [Scopus] Meech, R., Mubarokah, N., Shivasami, A., Rogers, A., Nair, P., Hu, D.G., et al. (2015). A Novel Function for UDP Glycosyltransferase 8: Galactosidation of Bile Acids. Molecular Pharmacology, 87(3) pp. 442-450. [10.1124/mol.114.093823] [Scopus] [PubMed] Hu, D.G., Meech, R., McKinnon, R.A. and Mackenzie, P. (2014). Transcriptional regulation of human UDP-glucuronosyltransferase genes. Drug Metabolism Reviews, 46(4) pp. 421-458. [10.3109/03602532.2014.973037] [Scopus] Zhuang, L., Hulin, J.A., Gromova, A., Nguyen, T.D., Yu, R., Liddle, C., et al. (2014). Barx2 and Pax7 have antagonistic functions in regulation of Wnt signaling and satellite cell differentiation. Stem Cells, 32(6) pp. 1661-1673. [10.1002/stem.1674] [Scopus] Hu, D.G., Meech, R., Lu, L., McKinnon, R. and Mackenzie, P. (2014). Polymorphisms and Haplotypes of the UDP-Glucuronosyltransferase 2B7 Gene Promoter. Drug Metabolism and Disposition, [10.1124/dmd.113.056630] [Scopus] Voronov, D., Gromova, A., Liu, D., Zoukhri, D., Medvinsky, A., Meech, R., et al. (2013). Transcription factors Runx1 to 3 are expressed in the lacrimal gland epithelium and are involved in regulation of gland morphogenesis and regeneration. Investigative Ophthalmology & Visual Science, 54(5) pp. 3115-3125. [10.1167/iovs.13-11791] [Scopus] Meech, R., Rogers, A., Zhuang, L., Lewis, B., Miners, J. and Mackenzie, P. (2012). Identification of Residues That Confer Sugar Selectivity to UDP-Glycosyltransferase 3A (UGT3A) Enzymes. Journal of Biological Chemistry, 287(29) pp. 24122-24130. [10.1074/jbc.M112.343608] [Scopus] Meech, R., Gonzalez, K., Barro, M., Gromova, A., Zhuang, L., Hulin, J.A., et al. (2012). Barx2 Is Expressed in Satellite Cells and Is Required for Normal Muscle Growth and Regeneration. Stem Cells, 30(2) pp. 253-265. [10.1002/stem.777] [Scopus] [Web Link] Meech, R., Miners, J., Lewis, B. and Mackenzie, P. (2012). The glycosidation of xenobiotics and endogenous compounds: Versatility and redundancy in the UDP glycosyltransferase superfamily. Pharmacology and Therapeutics, 134(2) pp. 200-218. [10.1016/j.pharmthera.2012.01.009] [Scopus] Tsau, C., Ito, M., Gromova, A., Hoffman, M., Meech, R. and Makarenkova, H. (2011). Barx2 and Fgf10 regulate ocular glands branching morphogenesis by controlling extracellular matrix remodelling. Development, 138(15) pp. 3307-3317. [10.1242/dev.066241] [Scopus] Mackenzie, P.I., Rogers, A., Elliot, D.J., Chau, N., Hulin, J.A., Miners, J.O., et al. (2011). The novel UDP glycosyltransferase 3A2: cloning, catalytic properties, and tissue distribution. Molecular Pharmacology, 79(3) pp. 472-478. [10.1124/mol.110.069336] [Scopus] Meech, R. and Mackenzie, P.I. (2010). UGT3A: novel UDP-glycosyltransferases of the UGT superfamily. Drug Metabolism Reviews, 42(1) pp. 45-54. [10.3109/03602530903205823] [Scopus] [Web Link] Meech, R., Gomez, M., Woolley, C., Barro, M., Hulin, J.A., Walcott, E.C., et al. (2010). The Homeobox Transcription Factor Barx2 Regulates Plasticity of Young Primary Myofibers. PLoS One, 5(7) pp. 1-9. [10.1371/journal.pone.0011612] [Scopus]