Vice President, Cancer Immunology
"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."
years at Genentech
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, 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.
Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and –independent pathways.
J. Cell Biol. 199:1117-1130.
Lo, B., G. Strasser, M. Sagolla, C.D. Austin, M. Juntilla, and I. Mellman (2012)
View Abstract on PubMed
As a cell biologist-immunologist with an interest in cancer, research in my laboratory bridges all of these topics in a cellular mechanism-based fashion.
On the immunology side, we have long been interested in understanding how dendritic cells (DCs) regulate the immune response to pathogens and cancer cells. We are currently examining the specializations that make DCs so adept at detecting pathogens and inflammatory signals, and presenting antigens to T cells. For example, one project has identified novel endosomal transporters that enable bacterially-derived components to reach the cytosol to reach key sensor proteins (NOD1, NOD2). These transporters also form a complex with the NODs and, for reasons yet unknown, are essential for DC endosomes and lysosomes to exhibit the characteristic tubular morphology they adopt directly after pathogen detection.
We have also begun to concentrate on how both DC and T cell function can be modulated to enhance anti-cancer immune responses in the context of cancer immunotherapy, an exciting and effective new approach that Genentech is aggressively pursuing. Our laboratory efforts explore the basic science underlying our drug discovery efforts.
On the cell biology side, we have developed a new approach to reconstituting the process of tumorigenesis ex vivo, using tissues isolated from embryonic mice harboring oncogenes and tumor suppressor genes whose activities can be switched on and off using chemical genetic approaches (for an example, see Lo et al., 2012). This approach has provided an unprecedented ability to ask specific questions regarding the cell biology and genetics of tumor formation, EMT, and metastasis by dissecting the actual functions and mechanisms associated with individual genes using molecular, biochemical and live cell imaging techniques.
Transcriptional programming of dendritic cells for enhanced MHC class II antigen presentationNature Immunology, 2013, ISSN: 1529-2908 View on PubMed
Endocytosis and cancerCold Spring Harbor perspectives in biology, 2013, ISSN: 1943-0264 View on PubMed
A Nobel Prize for membrane traffic: Vesicles find their journey's endJournal of Cell Biology, 2013, ISSN: 0021-9525 View on PubMed
Antibody Therapeutics in CancerScience, 2013, ISSN: 0036-8075 View on PubMed
MARCH1-mediated MHCII ubiquitination promotes dendritic cell selection of natural regulatory T cellsJournal of Experimental Medicine, 2013, ISSN: 0022-1007 View on PubMed
Antigen delivery to early endosomes eliminates the superiority of human blood BDCA3+ dendritic cells at cross presentationJournal of Experimental Medicine, 2013, ISSN: 0022-1007 View on PubMed
Lkb1 regulates organogenesis and early oncogenesis along AMPK-dependent and -independent pathwaysJournal of Cell Biology, 2012, ISSN: 0021-9525 View on PubMed
Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cellsBlood, 2012, ISSN: View on PubMed
Influenza a virus infection of human primary dendritic cells impairs their ability to cross-present antigen to CD8 T cellsPLoS Pathogens, 2012, ISSN: 1553-7366 View on PubMed
AMP-activated Protein Kinase (AMPK) Activation and Glycogen Synthase Kinase-3 beta (GSK-3β) Inhibition Induce Ca2+-independent Deposition of Tight Junction Components at the Plasma Membrane.JOURNAL OF BIOLOGICAL CHEMISTRY, 2011, V286, N19, MAY 13, pp 16879-16890. ISSN: 0021-9258. View on PubMed
Designing Vaccines Based on Biology of Human Dendritic Cell Subsets.Immunity, 2010, ISSN: 1074-7613
Cell Biology Redux.Molecular Biology of the Cell, 2010, ISSN: 1939-4586
Hepatocyte Growth Factor stimulated cell scattering requires ERK and Cdc42-dependent tight junction disassembly.Biochemical and Biophysical Research Communications, 2010, ISSN: 0006-291X
Monocyte-Derived Dendritic Cells Exhibit Increased Levels of Lysosomal Proteolysis as Compared to Other Human Dendritic Cell Populations.PLoS ONE, 2010, ISSN: 1932-6203
β-catenin balances immunity.Science, 2010, ISSN: 1095-9203
Trafficking Guidance Receptors.Cold Spring Harbor Perspectives in Biology, 2010, ISSN: 1943-0264
Inflammasome-activating nanoparticles as modular systems for optimizing vaccine deliveryVaccine, 2009, ISSN: 0264-410X
Spatial control of EGF receptor activation by reversible dimerization on living cells.Nature, 2010, ISSN: 1476-4687
Mature dendritic cells use endocytic receptors to capture and present antigens.Proceedings of the National Academy of Sciences, 2010, ISSN: 0027-8424
The prioritization of cancer antigens: a National Cancer Institute pilot project for the acceleration of translational research.Clinical Cancer Research, 2009, ISSN: 1078-0432
Membrane proteins follow multiple pathways to the basolateral cell surface in polarized epithelial cells.Journal of Cell Biology, 2009, ISSN: 0021-9525
Essential and unique roles of PIP5K-γ and -α in Fcγ receptor-mediated phagocytosisJournal of Cell Biology, 2009, ISSN: 0021-9525
Host ER-parasitophorous vacuole interaction provides a route of entry for antigen cross-presentation in Toxoplasma gondii-infected dendritic cells.Journal of Experimental Medicine, 2009, ISSN:
- The Rockefeller University, Postdoctoral Fellow – 1980
- Yale University School of Medicine, Genetics, Ph.D. – 1978
- Oberlin College and Conservatory of Music, Biology, B.A. – 1973
Awards & Honors
- Distinguished Lecturer, European Molecular Biology Laboratory – 2012
- Member, National Academy of Sciences – 2011
- Member, American Academy of Arts & Sciences – 2005
- Foreign Member, European Molecular Biology Orgainzation – 2004
- Phillip Levine Lecture, The Rockefeller University – 2004
- Editor in Chief, The Journal of Cell Biology – 1999-2008
- Newton-Abraham Professor, University of Oxford – 1998-99
- Yale Science and Engineering Society Medal – 1985
- President's Research Development Award, Leukemia Society of America – 1983
- Junior Faculty Research Award, American Cancer Society – 1981
- Swebilius Award – 1981
- Fellow of the Leukemia Society of America – 1978
- President’s Lecture, Memorial Sloan-Kettering Cancer Center –
- Director’s Lecture, The National Institutes of Health –
- Founder, CGI Pharma –
- ISI Highly Cited Author –