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| Qualifications |
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1988 B.Sc, University of Glasgow, Scotland, UK. Immunology 1992 M.Sc, University of Manchester, England, UK. Immunology & Cell Biology 1996 Ph.D, King’s College London. Vascular Biology & Immunology |
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| Research Interests |
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The principal research interest of this lab is to understand the molecular basis of signal transduction pathways that control gene expression in immune and inflammatory responses and to determine how deregulation of these mechanisms contribute to disease. Our work focuses on the inducible transcription factor NF-kB that is critical for a range of cellular functions including inflammation, innate and adaptive immunity and lymphocyte development. Although important components of some pathways leading to NF-kB activation are known, we remain far from understanding the complex layers of biochemical mechanisms that regulate its activity. Consequently, we aim to combine cellular, biochemical, molecular, and in vivo genetic approaches to define the nature of the signals that converge on this ubiquitously expressed transcription factor. Understanding these mechanisms will be of tremendous clinical importance as uncontrolled or inappropriate NF-kB activation contributes to a range of pathological conditions that include cardiovascular disease, some forms of cancer and certain viral, bacterial and parasite infections. Hence, one of our major objectives is to identify and characterize novel regulatory elements of distinct NF-kB signaling pathways that present realistic targets for therapeutic intervention. Our current areas of research are:
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| Selected Publications |
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May, M.J., D’Acquisto, F., Madge, L.A. , Glockner, J., Pober, J.S. & Ghosh,S. (2000). Selective inhibition of NF- k B activation by a peptide that blocks the interaction of NEMO with the I k B kinase complex.Science.289: 1550-1554. Zhong, H., May, M.J., Jimi, E., & Ghosh, S. (2002). Phosphorylation of NF- k B determines its association with CBP/p300 or HDAC-1. Mol. Cell. 9: 625-636. Thomas, R.P., Farrow, B.J., Kim, S-H., May, M.J., Hellmich, M.R. & Evers, B.M. (2002). Selective targeting of the NF- k B pathway enhances TRAIL-mediated pancreatic cancer cell death. Surgery. 132: 127-134. May, MJ., Marienfeld, R.B. & Ghosh, S. (2002) Characterization of the I k B-kinase NEMO binding domain (NBD). J. Biol. Chem. 277: 45992-46000. Marienfeld, R., May, M.J., Berberich, I. , Serfling, E., Ghosh, S. and Neumann, M. (2003). RelB forms transcriptionally inactive complexes with RelA/p65. J.Biol.Chem. 278: 19852-19860. Paria B.C., Malik A.B., Kwiatek A.M., Rahman A., May M.J., Ghosh S. and Tiruppathi C. (2003). Tumor necrosis factor-alpha induces nuclear factor-kappa B-dependent TRPC1 expression in endothelial cells. J.Biol.Chem. 278: 37195-37203. Jimi, E., Aoki, K., Saito, H., D’Acquisto, F., May, M.J., Nakamura, I., Sudo, T., Ohya, K, & Ghosh, S. (2004) Selective Inhibition of NF- k B Blocks Osteoclastogenesis and Prevents Inflammatory Bone Destruction In Vivo.Nature Medicine. 10: 617-624. May, M.J. , Larsen, S.E., Shim, J-H., Madge, L.A. & Ghosh, S. (2004) A novel ubiquitin-like domain in I k B Kinase b is critical for the functional activity of the kinase. J.Biol.Chem. 279: 45528-45539. Oakley, F., Meso, M., Iredale, J.P., Marek, C.J., Zhou, X., May, M.J., Milward-Sadler, H., Wright, M.C. & Mann, D.A. (2005) The IKK inhibitor sulfasalazine stimulates JNK-dependent hepatic stellate cell apoptosis and accelerates recovery from rat liver fibrosis .Gastroenterology. 128: 108-120. Nadjar, A., Tridon, V., May, M.J., Ghosh, S., Dantzer, R., Amedee, T. & Parnet, P. NF- k B activates in vivo the synthesis of inducible Cox-2 in the brain. (2005) J.Cerebr.Blood.F.Met. 25: 1047-1059 . Tas, S.W., de Jong, E.C., Hajji, N., Kapsenberg, M.L., May, M.J., Ghosh, S., Vervoordeldonk, M.J. & Tak, P.P. (2005) Selective inhibition of NF- k B in dendritic cells by the NEMO-binding domain peptide efficiently blocks maturation and prevents T cell proliferation and polarization. Eur.J.Immunol. 35: 1164-1174. Nadjar, A, Bluthe, R-M., May, M.J., Dantzer, R. & Parnet, P. (2005) Inactivation of the cerebral NF k B pathway inhibits interleukin-1ß-induced sickness behavior and c-Fos expression in various brain nuclei. Neuropsychopharmacology. 30: 1492-1499. Shapira, S., Harb, O., Magret, J., Matrajt, M., Han, J., Hoffman, A., Freedman, B., May, M.J., Roos, D., & Hunter, C.A. (2005) Initiation and termination of NF- k B signaling by the intracellular protozoan parasite Toxoplasma gondii. J.Cell Science. 118: 3501-3508. Madge, L.A. & May, M.J. LIGHT and Lymphotoxin- a 1 b 2 activate classical and non-canonical NF- k B and induce pro-inflammatory and lymphoid-specific gene expression in human umbilical vein endothelial cells. (Submitted; 2005). |
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