Dr Ruaidhri Carmody

Reader (Molecular Biosciences)

telephone: 330 3801
email: Ruaidhri.Carmody@glasgow.ac.uk

Davison Building 241

Research interests

Since its discovery some 20 years ago, the NF-κB family of proteins has become one of the most important transcription factors relevant to human health and disease. This is due in large part to its pleiotropic effects, its tightly regulated inducibility and its central role in the control of immunity and inflammation. While intense study of the receptor associated events leading to NF-κB activation has resulted in the identification of a complex cytoplasmic regulatory network, comparatively little is known about the regulation of NF-κB nucleus. My research interests lie in identifying key nuclear events that shape the transcriptional outcome of receptor activated NF-κB. We identified the nuclear IκB protein Bcl-3 as a key regulator of NF-κB transcriptional activity during Toll-like receptor signalling. The interaction of Bcl-3 with NF-κB p50 homodimers prevents their ubiquitination and proteasomal degradation, leading to the formation of a stable repressor complex. This Bcl-3:p50 homodimer complex competes with transcriptionaly competent NF-κB dimers for a finite number of DNA binding sites, thereby negatively regulating gene transcription. This Bcl-3:p50 homodimer complex is also of critical importance in promoting a non-responsive state in macrophage following chronic or repeated stimulation through Toll-like receptors, termed tolerance, which is essential for limiting inflammation-induced injury to host tissue. We are very interested in identifying and understanding additional regulators of Toll-like receptor tolerance at the transcriptional level.

More recently, we have identified the first de-ubiquitinase enzyme for NF-κB, Ubiquitin Specific Protease 7, and revealed that the balance of ubiquitination and de-ubiquitination of the NF-κB subunit p65 in the nucleus is fundamental to the control of target gene transcription.

We continue to identify nuclear regulatory events which shape the activity of NF-κB. In addition to revealing fundamental aspects of the control of transcription during inflammation our work also identifies novel therapeutic targets relevant to the treatment of inflammatory disease.

Research groups

Molecular Pharmacology & Cellular Signalling

Publications

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Number of items: 40.

2023

Jaffery, H. et al. (2023) IĸB Protein BCL3 as a controller of osteogenesis and bone health. Arthritis and Rheumatology, 75(12), 2148-2160-2148-2160. (doi: 10.1002/art.42639) (PMID:37410754)

2021

Kok, F. O., Wang, H., Riedlova, P. , Goodyear, C. S. and Carmody, R. J. (2021) Defining the structure of the NF-ĸB pathway in human immune cells using quantitative proteomic data. Cellular Signalling, 88, 110154. (doi: 10.1016/j.cellsig.2021.110154) (PMID:34562606)

Somma, D. , Kok, F. O., Kerrigan, D., Wells, C. A. and Carmody, R. J. (2021) Defining the role of nuclear factor NF-κB p105 subunit in human macrophage by transcriptomic analysis of NFKB1 knockout THP-1 cells. Frontiers in Immunology, 12, 669906. (doi: 10.3389/fimmu.2021.669906) (PMCID:PMC8548695)

2020

Mitxitorena, I., Somma, D. , Mitchell, J. P., Lepistö, M., Tyrchan, C., Smith, E. L., Kiely, P. A., Walden, H. , Keeshan, K. and Carmody, R. J. (2020) The deubiquitinase USP7 uses a distinct ubiquitin-like domain to deubiquitinate NF-ĸB subunits. Journal of Biological Chemistry, 295(33), pp. 11754-11763. (doi: 10.1074/jbc.RA120.014113) (PMID:32587091) (PMCID:PMC7450122)

Sarrou, E. , Richmond, L., Carmody, R. J. , Gibson, B. and Keeshan, K. (2020) CRISPR gene editing of murine blood stem and progenitor cells induces MLL-AF9 chromosomal translocation and MLL-AF9 leukaemogenesis. International Journal of Molecular Sciences, 21(12), 4266. (doi: 10.3390/ijms21124266) (PMID:32549410) (PMCID:PMC7352880)

2019

Collins, P. E., Somma, D. , Kerrigan, D., Herrington, F., Keeshan, K. R. , Nibbs, R. J.B. and Carmody, R. J. (2019) The IκB-protein BCL-3 controls toll-like receptor-induced MAPK activity by promoting TPL-2 degradation in the nucleus. Proceedings of the National Academy of Sciences of the United States of America, 116(51), pp. 25828-25838. (doi: 10.1073/pnas.1900408116) (PMID:31772019) (PMCID:PMC6926074)

Smith, E. L., Somma, D. , Kerrigan, D., McIntyre, Z., Cole, J. J., Liang, K. L., Kiely, P. A., Keeshan, K. and Carmody, R. J. (2019) The regulation of sequence specific NF-ĸB DNA binding and transcription by IKKβ Phosphorylation of NF-ĸB p50 at Serine 80. Nucleic Acids Research, 47(21), pp. 11151-11161. (doi: 10.1093/nar/gkz873) (PMID:31598684) (PMCID:PMC6868378)

2018

Butcher, S. K., O'Carroll, C. E., Wells, C. A. and Carmody, R. J. (2018) Toll-like receptors drive specific patterns of tolerance and training on restimulation of macrophages. Frontiers in Immunology, 9, 933. (doi: 10.3389/fimmu.2018.00933) (PMID:29867935) (PMCID:PMC5960718)

Salomé, M. , Magee, A., Yalla, K., Chaudhury, S. , Sarrou, E. , Carmody, R. J. and Keeshan, K. (2018) A Trib2-p38 axis controls myeloid leukaemia cell cycle and stress response signalling. Cell Death and Disease, 9(5), 443. (doi: 10.1038/s41419-018-0467-3) (PMID:29670085) (PMCID:PMC5906628)

Mitchell, J. P. and Carmody, R. J. (2018) NF-κB and the Transcriptional Control of Inflammation. In: Loos, F. (ed.) Transcriptional Gene Regulation in Health and Disease. Series: International review of cell and molecular biology (335). Elsevier, pp. 41-84. ISBN 9780128123393 (doi: 10.1016/bs.ircmb.2017.07.007)

2017

Carmody, R. and Keeshan, K. (2017) The Tribble with APL: a new road to therapy. Cancer Cell, 31(5), pp. 612-613. (doi: 10.1016/j.ccell.2017.04.011) (PMID:28486101)

Ahmed, A., Wan, X., Mitxitorena, I., Lindsay, A. J., Pandolfi, P. P., McCaffrey, M. W., Keeshan, K. , Chen, Y. H. and Carmody, R. J. (2017) Regulation of NF-κB by PML and PML-RARα. Scientific Reports, 7, 44539. (doi: 10.1038/srep44539) (PMID:28317833) (PMCID:PMC5357907)

2016

Liang, K. L., Paredes, R., Carmody, R. , Eyers, P. A., Meyer, S., McCarthy, T. V. and Keeshan, K. (2016) Human TRIB2 oscillates during the cell cycle and promotes ubiquitination and degradation of CDC25C. International Journal of Molecular Sciences, 17(9), 1378. (doi: 10.3390/ijms17091378) (PMID:27563873) (PMCID:PMC5037658)

Herrington, F. D., Carmody, R. J. and Goodyear, C. S. (2016) Modulation of NF-κB signaling as a therapeutic target in autoimmunity. Journal of Biomolecular Screening, 21(3), pp. 223-242. (doi: 10.1177/1087057115617456) (PMID:26597958)

Pratt, A. G., Anderson, A. E., Carmody, R. J. and Isaacs, J. D. (2016) B cell lymphoma 3 (Bcl-3) in CD4+ T cell mediated RA pathogenesis: Comment on the article by Meguro et al. Arthritis and Rheumatology, 68(3), pp. 770-771. (doi: 10.1002/art.39509) (PMID:26605875)

2015

Ning, Z. et al. (2015) Regulation of SPRY3 by X chromosome and PAR2-linked promoters in an autism susceptibility region. Human Molecular Genetics, 24(25), p. 7450. (doi: 10.1093/hmg/ddv448) (PMID:26534778)

Ning, Z. et al. (2015) Regulation of SPRY3 by X chromosome and PAR2-linked promoters in an autism susceptibility region. Human Molecular Genetics, 24(18), pp. 5126-5141. (doi: 10.1093/hmg/ddv231) (PMID:26089202)

Collins, P. E., Grassia, G., Colleran, A., Kiely, P. A., Ialenti, A., Maffia, P. and Carmody, R. J. (2015) Mapping the interaction of B cell Leukemia 3 (BCL-3) and nuclear factor κB (NF-κB) p50 identifies a BCL-3-mimetic anti-inflammatory peptide. Journal of Biological Chemistry, 290(25), pp. 15687-15696. (doi: 10.1074/jbc.M115.643700) (PMID:25922067) (PMCID:PMC4505479)

Colleran, A., Collins, P. E. and Carmody, R. J. (2015) Assessing sites of NF-κB DNA binding using chromatin immunoprecipitation. In: May, M.J. (ed.) NF-kappaB Methods and Protocols. Series: Methods in molecular biology (1280). Humana Press, pp. 47-59. ISBN 9781493924226 (doi: 10.1007/978-1-4939-2422-6_4)

Collins, P. E. and Carmody, R. J. (2015) The regulation of endotoxin tolerance and its impact on macrophage activation. Critical Reviews in Immunology, 35(4), pp. 293-323. (doi: 10.1615/CritRevImmunol.2015015495) (PMID:26757393)

Collins, P. E., Colleran, A. and Carmody, R. J. (2015) Control of NF-κB subunits by ubiquitination. In: May, M.J. (ed.) NF-kappaB Methods and Protocols. Series: Methods in molecular biology (1280). Humana Press, pp. 355-370. ISBN 9781493924226 (doi: 10.1007/978-1-4939-2422-6_21)

Collins, P. E., O'Carroll, C. and Carmody, R. J. (2015) Measurement of NF-κB transcriptional activity and identification of NF-κB cis-regulatory elements using luciferase assays. In: May, M.J. (ed.) NF-kappaB Methods and Protocols. Series: Methods in molecular biology (1280). Humana Press, pp. 25-43. ISBN 9781493924226 (doi: 10.1007/978-1-4939-2422-6_3)

2014

Collins, P. E., Kiely, P. A. and Carmody, R. J. (2014) Inhibition of transcription by B cell leukaemia 3 (Bcl-3) requires interaction with nuclear factor (NF)-κB p50. Journal of Biological Chemistry, 289(10), pp. 7059-7067. (doi: 10.1074/jbc.M114.551986)

O'Carroll, C., Fagan, A., Shanahan, F. and Carmody, R.J. (2014) Identification of a unique hybrid macrophage-polarization state following recovery from lipopolysaccharide tolerance. Journal of Immunology, 192(1), pp. 427-436. (doi: 10.4049/jimmunol.1301722)

Williams, M. T.S. et al. (2014) Interleukin-15 enhances cellular proliferation and up-regulates CNS homing molecules in pre-B acute lymphoblastic leukemia. Blood, 123(20), pp. 3116-3127. (doi: 10.1182/blood-2013-05-499970) (PMID:24700781)

2013

Regan, T., Nally, K., Carmody, R. , Houston, A., Shanahan, F., Macsharry, J. and Brint, E. (2013) Identification of TLR10 as a key mediator of the inflammatory response to Listeria monocytogenes in intestinal epithelial cells and macrophages. Journal of Immunology, 191(12), pp. 6084-92. (doi: 10.4049/jimmunol.1203245) (PMID:24198280)

O'Carroll, C., Moloney, G., Hurley, G., Melgar, S., Brint, E., Nally, K., Nibbs, R.J. , Shanahan, F. and Carmody, R.J. (2013) Bcl-3 deficiency protects against dextran-sodium sulphate-induced colitis in the mouse. Clinical and Experimental Immunology, 173(2), pp. 332-342. (doi: 10.1111/cei.12119) (PMID:23607276)

Colleran, A., Collins, P. E., O'Carroll, C., Ahmed, A., Mao, X., McManus, B., Kiely, P. A., Burstein, E. and Carmody, R.J. (2013) Deubiquitination of NF- B by Ubiquitin-Specific Protease-7 promotes transcription. Proceedings of the National Academy of Sciences of the United States of America, 110(2), pp. 618-623. (doi: 10.1073/pnas.1208446110)

2012

Yan, Q., Carmody, R.J. , Qu, Z., Ruan, Q., Jager, J., Mullican, S.E., Lazar, M.A. and Chen, Y.H. (2012) Nuclear factor- B binding motifs specify Toll-like receptor-induced gene repression through an inducible repressosome. Proceedings of the National Academy of Sciences of the United States of America, 109(35), pp. 14140-14145. (doi: 10.1073/pnas.1119842109)

O'Gorman, D. M., O'Carroll, C. and Carmody, R. J. (2012) Evidence that marine-derived, multi-mineral, Aquamin inhibits the NF-κB signaling pathway in vitro. Phytotherapy Research, 26(4), pp. 630-2. (doi: 10.1002/ptr.3601) (PMID:22034197)

2011

Kreisel, D., Sugimoto, S., Tietjens, J., Zhu, J., Yamamoto, S., Krupnick, A.S., Carmody, R.J. and Gelman, A.E. (2011) Bcl3 prevents acute inflammatory lung injury in mice by restraining emergency granulopoiesis. Journal of Clinical Investigation, 121(1), pp. 265-276. (doi: 10.1172/JCI42596)

2010

Ruan, Q., Zheng, S.-J., Palmer, S., Carmody, R.J. and Chen, Y.H. (2010) Roles of Bcl-3 in the pathogenesis of murine type 1 diabetes. Diabetes, 59(10), pp. 2549-2557. (doi: 10.2337/db10-0480)

2009

Ludwinski, M.W., Sun, J., Hilliard, B., Gong, S., Xue, F., Carmody, R.J. , DeVirgiliis, J. and Chen, Y.H. (2009) Critical roles of Bim in T cell activation and T cell–mediated autoimmune inflammation in mice. Journal of Clinical Investigation, 119(6), pp. 1706-1713. (doi: 10.1172/JCI37619)

2008

Sun, H. et al. (2008) TIPE2, a negative regulator of innate and adaptive immunity that maintains immune homeostasis. Cell, 133(3), pp. 415-426. (doi: 10.1016/j.cell.2008.03.026)

2007

Carmody, R.J. , Ruan, Q., Palmer, S., Hilliard, B. and Chen, Y.H. (2007) Negative regulation of toll-like receptor signaling by NF-κB p50 ubiquitination blockade. Science, 317(5838), pp. 675-678. (doi: 10.1126/science.1142953)

Carmody, R. J. , Ruan, Q., Liou, H.-C. and Chen, Y. H. (2007) Essential roles of c-Rel in TLR-induced IL-23 p19 gene expression in dendritic cells. Journal of Immunology, 178(1), pp. 186-91.

Carmody, R. J. and Chen, Y. H. (2007) Nuclear factor-kappaB: activation and regulation during toll-like receptor signaling. Cellular and Molecular Immunology, 4(1), pp. 31-41.

2006

Carmody, R. J. , Maguschak, K. and Chen, Y. H. (2006) A novel mechanism of nuclear factor-kappaB regulation by adenoviral protein 14.7K. Immunology, 117(2), pp. 188-95. (doi: 10.1111/j.1365-2567.2005.02277.) (PMID:16423054) (PMCID:PMC1782211)

2003

Xu, L., Hilliard, B., Carmody, R. J. , Tsabary, G., Shin, H., Christianson, D. W. and Chen, Y. H. (2003) Arginase and autoimmune inflammation in the central nervous system. Immunology, 110(1), pp. 141-8. (doi: 10.1046/j.1365-2567.2003.01713.x) (PMCID:PMC1783013)

2002

Carmody, R. J. , Hilliard, B., Maguschak, K., Chodosh, L. A. and Chen, Y. H. (2002) Genomic scale profiling of autoimmune inflammation in the central nervous system: the nervous response to inflammation. Journal of Neuroimmunology, 133(1-2), pp. 95-107. (doi: 10.1016/S0165-5728(02)00366-1)

This list was generated on Thu Nov 21 02:58:54 2024 GMT.

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