"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."
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, where I was chair of my department, 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.
During my 20+ years in the Department of Cell Biology at Yale Medical School, I mentored over 60 graduate students and postdoctoral fellows. Many of these young scientists have gone on to wonderfully successful scientific careers at major universities and research institutions around the world. This is by far my proudest accomplishment in science. While the lab group at Yale was quite a bit larger (25-30) than it is at Genentech, my philosophy towards mentorship has not changed. I believe in challenging each and every individual who enters the group to “aim high” and attempt to tackle a major problem of great significance. It is as much effort to do something that is derivative as it is to do something that is exciting, so why not at least try for something exciting? I believe in allowing people to grow and think for themselves, to learn how to frame problems and to plot the best paths to answer them. These are scientific skills that will be required for a successful career in any setting be it academia, industry, or elsewhere. My role is to guide the process by providing whatever wisdom I have gained from my own experience and by ensuring that every postdoc has a chance to reach his/her full potential by developing the highest level of scientific creativity, critical thought, communications skills, and experimental rigor.
My group’s long interest in understanding the cellular mechanisms of the immune response has increasingly focused on the problem of cancer immunology & immunotherapy. We have now established an entire department devoted to this effort, and postdocs in my group seek to understand how checkpoint inhibitors (eg anti-PD-L1), vaccines, immune agonists and their combinations work to produce durable anti-cancer responses. One feature that makes our work so exciting is that we draw upon results from Genentech’s clinical trials to identify and define problems to investigate in the lab, a process we have come to call “reverse translation”.
Projects are changing all the time and range from the very basic analysis of mechanism to the integrated consideration of human clinical biomarker data. Basic research is the main focus, however, and currently includes a variety of projects, for example: (i) understanding how negative regulators on T cells such as PD-1 act to limit T cell responses, using a new cell-free reconstitution system; (ii) understanding how dendritic cells cross-present tumor-derived antigens to initiate anti-cancer T cell responses; (iii) probing the often surprising ability of targeted anti-cancer agents to augment rather than inhibit T cell immunity; (iv) predicting immunogenic T cell epitopes in human cancer; (v) real time imaging of T cell function in tumors using genetically modified cells combined with new imaging approaches such as lattice light sheet microscopy.
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