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Metabolism Branch

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Since its inception in 1956, the Metabolism Branch has been an exemplar of translational research. Its investigators combine basic research, preclinical investigation, and drug development with innovative, therapeutic clinical trials that have as their scientific basis fundamental research performed in the branch. The primary interest of the branch concerns the regulation of the immune response and the definition of disorders of immunoregulation that underlie immunodeficiency and neoplastic diseases. The fundamental laboratory-based studies concern:

- molecular biology of human lymphoid malignancies (Lou Staudt); characterization of gene expression patterns in human lymphomas and leukemias using the cDNA microarray to provide a new molecular classification of leukemia and lymphoma;

- identification of the Type-I interferon receptor and singnaling pathways and evaluation of their therapeutic potential (Kathryn Zoon)

- identification and purification of novel interleukin molecules including IL-15, codiscovered by Dr. Waldmann's group, as well as the molecular analysis of the multichain IL-2/IL-15 receptors expressed on normal and malignant lymphocytes (Thomas Waldmann);

- definition of the molecular defects in patients with primary immunodeficiency diseases (David Nelson);

- preclinical and translational development of gene therapy protocols (John Morris).

A second focus of the branch is to translate fundamental insights into new approaches for prevention, diagnosis, and treatment of human cancer and immunodeficiency diseases. Studies on T lymphocyte recognition of antigens presented by MHC-encoded molecules provide the molecular basis for trials evaluating cancer vaccines aimed at inducing cytotoxic lymphocytes reactive with mutant oncogene products common in human cancers, and developing peptide vaccines for HIV (Jay Berzofsky, John Janik, and John Morris). An additional clinical emphasis has as its scientific basis the demonstration that IL-2 receptors are constitutively expressed by leukemic cells but not by normal cells. This difference in receptor expression is being exploited in clinical trials employing humanized anti-IL-2R antibodies armed with alpha- and beta-emitting radionuclides to treat patients with leukemia (John Morris, John Janik, and Thomas Waldmann).

- The codiscovery of IL-15 and the demonstration of its pathogenic role in leukemia and autoimmune disease provides the scientific basis for the use of IL-15 receptor directed monoclonal antibody mediated trials in these disorders (Thomas Waldmann)

This page was last updated on 2/11/2008.