Much of our research focuses on three projects centered around transcription factor NF-kB. In one project, we seek to understand the cellular and molecular mechanisms by which altered NF-kB activity contributes to a variety of human cancers, especially lymphoid cell cancers. For example, we have found that many human B-cell lymphomas have chronically high levels of nuclear NF-kB activity that is required for their growth and survival. More recently, we have also been investigating the role of NF-kB co-activator proteins called HATs (histone acectyltransferases) in human B-cell lymphoma.
In collaborative studies with Drs. John Porco, Adrian Whitty, and Karen Allen in the Chemistry Department at BU, we are characterizing natural and synthetic inhibitors of NF-kB signaling. Many of these inhibitors are derivatives of natural products, and may have anti-cancer or anti-inflammatory activities. In this project, we are also characterizing the structure and function of a protein called NEMO, which is an upstream adaptor protein for the NF-kB pathway and is mutated in certain human immunodeficiencies.
Finally, we are studying the evolutionary origins of the NF-kB pathway by characterizing NF-kB genes and proteins in simple marine organisms, such as the sea anemone Nematostella vectensis. This research may have relevance to the mechanisms by which simple marine organisms deal with the environmental stress that is currently impacting sensitive marine ecosystems. These studies are being carried out in collaboration with Drs. Les Kaufman, John Finnerty and Trevor Siggers (Biology Department, Boston University).
- Brennan JJ, Gilmore TD (2018) Evolutionary origins of Toll-like receptor signaling. Molecular Biology and Evolution 35: 1576-1587.
- Friedman LE, TD Gilmore, JR Finnerty (2018) Intraspecific variation in peroxide sensitivity in the starlet sea anemone Nematostella vectensis, an estuarine cnidarian. PLoS ONE 13: e0188265.
- Williams LM, Fuess LE, Brennan JJ, Mansfield KM, Salas-Rodriguez E, Welsh J, Awtry J, Banic S, Chacko C, Chezian A, Dowers D, Estrada F, Hsieh Y-H, Kang J, Li W, Malchiodi Z, Malinowski J, Matuszak S, McTigue IV T, Mueller D, Nguyen B, Nguyen M, Nguyen P, Nguyen S, Njoku N, Patel K, Pellegrini W, Pliakas T, Qadir D, Ryan E, Schiffer A, Thiel A, Yunes SA, Spilios KE, Pinzón C JH, Mydlarz LD, Gilmore TD (2018) A conserved Toll-like receptor-to-NF-kB signaling pathway in the endangered coral Orbicella faveolata. Developmental & Comparative Immunology 79: 128-136.
- Mansfield KM, Carter NM, Nguyen L, Cleves PA, Alshanbayeva A, Williams LM, Penvose A, Finnerty JR, Weis VM, Siggers T, Gilmore TD (2017) Transcription factor NF-kB is modulated by symbiotic status in a sea anemone model of cnidarian bleaching. Scientific Reports 7: 16025.
- Brennan JJ, Messerschmidt JL, Williams LM, Matthews BJ, Reynoso M, Gilmore TD (2017) Sea anemone model has a single Toll-like receptor that can function in pathogen detection, NF-kB signal transduction, and development. Proceedings of the National Academy of Sciences USA 114: E10122-E10131.
- Haery L, Mussakhan S, Waxman DJ, Gilmore TD (2016) Evidence for an oncogenic modifier role for mutant histone acetyltransferases in diffuse large B-cell lymphoma. Leukemia & Lymphoma 57: 2661-2671.
- Zhou L, Yeo A, Ballorano C, Weber U, Allen KN, Gilmore TD, Whitty A (2014) Disulfide-mediated stabilization of the IκB kinase binding domain of NF-kB essential modulator (NEMO). Biochemistry 53: 7929-7944.
- Wolenski FS, Layden MJ, Martindale MQ, Gilmore TD, Finnerty JR (2013) Characterizing the spatiotemporal expression of RNAs and proteins in the starlet sea anemone, Nematostella vectensis. Nature Protocols 8: 900-915.
- BB522 Molecular Biology Laboratory
- BI576 Carcinogenesis