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).
- 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.
- Haery L, Thompson RC, Gilmore TD (2015) Histone acetyltransferases and histone deacetylases in B- and T-cell development, physiology and malignancy. Genes & Cancer 6: 184-213.
- Yeo AT, Chennamadhavuni S, Whitty A, Porco Jr JA, Gilmore TD (2015) Inhibition of oncogenic transcription factor REL by the natural product derivative calafianin monomer 101 induces proliferation arrest and apoptosis in human B-lymphoma cell lines. Molecules 20: 7474-7494.
- Haery L, Lugo-Pico JG, Henry RA, Andrews AW, Gilmore TD (2014) Histone acetyltransferase-deficient p300 mutants in diffuse large B-cell lymphoma have altered transcriptional regulatory activities and are required for optimal cell growth. Molecular Cancer 13: 29.
- 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.
- Wolenski FS, Bradham CA, Finnerty JR, Gilmore TD (2013) NF-kB is required for cnidocyte development in the sea anemone Nematostella vectensis. Developmental Biology, 373: 205-215.
- Gilmore TD, Wolenski FS (2012) NF-kB: where did it come from and why? Immunological Reviews, 246: 14-25.
- BB522 Molecular Biology Laboratory
- BI576 Carcinogenesis