""""""""Dr. Waldmann's studies have focused on the role played by the IL-2-IL-2 receptor system in normal and abnormal T-cell function and the use of these insights to develop IL-2R directed therapy for leukemia. As part of his study of HTLV-I-associated adult T-cell leukemia (ATL), Dr. Waldmann, co-discovered a cytokine, IL-15, that stimulates T-cell proliferation and NK cell development. Dr. Waldmann showed that IL-15 message includes a number of elements that are impediments to its translation. In particular, the 5' UTR of the normal human IL-15 message is burdened with 10 upstream AUGs that interfere with efficient IL-15 translation. Furthermore, the unusually long 48 amino acid leader sequence and a cis- acting element in the 3' mature protein coding region interfere with this process. As a hypothesis he proposed that by maintaining a pool of translationally inactive IL-15 mRNA cells can readily respond to an intracellular infection by unburdening the IL-15 message transforming it into one that can be effectively translated.""""""""

National Institute of Health (NIH)
National Cancer Institute (NCI)
Intramural Research (Z01)
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Metabolism Study Section (MET)
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National Cancer Institute Division of Clinical Sciences
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Yu, P; Petrus, M N; Ju, W et al. (2015) Augmented efficacy with the combination of blockade of the Notch-1 pathway, bortezomib and romidepsin in a murine MT-1 adult T-cell leukemia model. Leukemia 29:556-66
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Bene, Laszlo; Kanyari, Zsolt; Bodnar, Andrea et al. (2007) Colorectal carcinoma rearranges cell surface protein topology and density in CD4+ T cells. Biochem Biophys Res Commun 361:202-7
Waldmann, T A (2007) Daclizumab (anti-Tac, Zenapax) in the treatment of leukemia/lymphoma. Oncogene 26:3699-703
Sato, Noriko; Patel, Hiral J; Waldmann, Thomas A et al. (2007) The IL-15/IL-15Ralpha on cell surfaces enables sustained IL-15 activity and contributes to the long survival of CD8 memory T cells. Proc Natl Acad Sci U S A 104:588-93
Waldmann, Thomas A (2007) Anti-Tac (daclizumab, Zenapax) in the treatment of leukemia, autoimmune diseases, and in the prevention of allograft rejection: a 25-year personal odyssey. J Clin Immunol 27:1-18
Perera, Liyanage P; Waldmann, Thomas A; Mosca, Joseph D et al. (2007) Development of smallpox vaccine candidates with integrated interleukin-15 that demonstrate superior immunogenicity, efficacy, and safety in mice. J Virol 81:8774-83

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