Ira Mellman Vice President: Research Oncology Profile | Education/Background | Top Scientific Papers | Awards & Honors

"I came to Genentech in the Spring of 2007 after more than 20 years as a faculty member at the Yale University School of Medicine. I was chair of my department (Cell Biology), a member of the Ludwig Institute for Cancer Research, and scientific director of the Yale Cancer Center. I ran a large and successful laboratory, I was surrounded by valued friends and colleagues, and I worked at one of the world's great universities. I had the perfect job, but I came to Genentech anyway. Why? Because at Genentech, I found that you can do your science at the highest possible level, engage the most profound problems you can imagine, have access to a research environment and infrastructure unimaginable at an academic institution, and also have the opportunity — and the challenge — to make a difference."

Current Projects "I am a cell biologist, a scientific 'generalist' who is interested in understanding the cellular mechanisms responsible for complex phenomena. I began my career unraveling the pathways and functional significance of endocytosis, and over the years, applied the insights achieved to elucidate two key problems: the generation and maintenance of cell polarity and the cell biological basis of the immune response. Although these two problems may appear disparate, they are united by a reliance on a common set of fundamental mechanisms grounded in molecular cell biology.

Our work on the immune response has concentrated on dendritic cells, a recently described cell type that is responsible for initiating all antigen-specific immune responses. A complex family of cells of as yet uncertain provenance, we have found that dendritic cells are uniquely proficient at stimulating T-cell responses because they exhibit an incredible array of specializations that optimize and regulate the endocytic and secretory pathways for antigen endocytosis, the generation of antigenic peptides bound to molecules of the major histocompatability complex (MHC), and the functional interaction with cognate T and B lymphocytes. Dendritic cells also have the ability to detect and respond differentially to different endogenous and microbial stimuli, guiding the T-cell activation to ensure appropriate immune responses to foreign invaders while maintaining 'tolerance' to one's own (self) antigens. We are continuing to unravel the complexities of the multiple types of dendritic cells, finding that our work lends itself with great immediacy to the development of strategies for therapeutic intervention: augmenting dendritic cell function to enhance responses to cancer, attenuating dendritic cell function to combat autoimmune and chronic inflammatory disease.

In the area of cell polarity, our group has been responsible for elucidating how protein-encoded signals control the distribution of membrane proteins to the appropriate domain of polarized cells such as epithelial cells and neurons. In anticipation of our move to Genentech, the group has now begun to focus more on a more systems-oriented aspect polarity: how membrane traffic and signal transduction are responsible for cellular and tissue morphogenesis, and how these processes break down in cancer. As always, we continue to use a decidedly broad array of techniques, varying from genetics to imaging to biochemistry. We work with key genes that control epithelial morphogenesis and signal transduction using in vitro systems as well as knock-out and knock-in mice. Recently, we have also begun using high resolution imaging techniques (e.g., total internal reflection fluorescence microscopy) to track the dynamics and function of individual signaling receptors on the surface of living cells, providing the first real insights into how these molecules actually work while in their natural surroundings.

My group's life here is remarkably similar to life at Yale in many important respects: we are in an environment that cherishes and promotes basic science, and that attracts some of the most talented young postdocs and students I have ever seen anywhere. They come not only because of the quality of the science, which is as high as one will find at any institution, but also because of the quality of the research infrastructure and the ability to apply one's efforts in basic science to real problems of human disease and drug discovery."

Inspiration/Vision "It is not yet the case that all of the major conceptual problems in biology have been defined or solved. Nevertheless, it is the case that a spectacular amount of fundamental information and understanding has been revealed over the past two to three decades. Perhaps the greatest challenge facing us now is learning how to apply the reductionist logic developed over this period to understanding and solving the far more complex problem of human biology and disease. We need to define this problem as a matter of the highest priority, and not simply a problem mentioned at the beginning of grant applications. Although academia is not yet optimally well suited to address this challenge, Genentech is. It is a challenge of profound importance, in both scientific and human terms. It is also one I know we can solve. Engaging this mission in the service of applying the best of basic science in the service of drug discovery is as intellectually demanding, exciting, and rewarding as any mission imaginable."