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Ira Mellman, professor of Cell Biology and Immunobiology and chairman of Cell Biology at Yale University School of Medicine, concentrates on fundamental questions of understanding membrane transport and cell morphogenesis as they apply to two distinct but complimentary problems: cell polarity and antigen processing.

Mellman focuses on the antigen-presenting dendritic cell (DC), work made possible by his continuing scientific and personal friendship with Ralph Steinman at Rockefeller. From 1978 to 1981, Mellman was a postdoctoral fellow in Steinman’s Laboratory of Cellular Physiology and Immunology.

Of all antigen-processing cells, DCs are by far the most professional and the most potent. Mellman’s group has applied a unique cell biological approach to unraveling the mechanisms underlying DC function, work which has already begun to elucidate several long-standing questions in immunology and to provide surprising new insights into fundamental cell biology.

Mellman and his colleagues have concentrated on DC “maturation,” the terminal stage in a differentiation process that converts DCs from immature sentinels that accumulate foreign and self-antigens in peripheral tissue to mature antigen-presenting cells that stimulate T lymphocytes in lymphoid tissues. This transformation is dramatic, involving a complete reorganization of the DC cytoplasm, a decrease in the capacity for endocytosis, an activation of the capacity to form immunogenic peptides bound to MHC molecules, and the translocation of the peptide-loaded MHC molecules to the cell surface. Many of these features appear to reflect a remarkable regulation of the DCs’ lysosomal apparatus, which is now being understood in molecular terms.

The work not only represents a unique combination of the fields of cell biology and immunology, but also serves to rationalize current and future attempts to modify the immune system for therapeutic benefit especially in cancer and chronic inflammation.

The Philip Levine Memorial Lecture was established in 1977 by Philip Levine (1900-1987) to bring speakers in the areas of cancer, genetics and immunology to The Rockefeller University. A member of the scientific staff at The Rockefeller Institute for Medical Research from 1925 to 1932, Levine studied human blood groups with Nobel laureate Karl Landsteiner.

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