"I lead the research program for one of the antibody-drug conjugates, which gratifyingly entered the clinic."
I studied membrane trafficking for my PhD (Kreis lab) and postdoc (Scheller lab) and was recruited to Genentech in 2001 to examine the endocytosis (internalization) of antibodies to cell surface cancer targets as part of the antibody-drug conjugate team. As well as helping to establish the rules for antibody trafficking and linker-drug selection, I lead the research program for one of the antibody-drug conjugates, which gratifyingly entered the clinic. We also explored the utility of antibody-siRNA conjugates and we are currently working on methods to visualize conjugate payload release within cells to test novel linkers.
Once here, I was recruited to the Hedgehog team to better understand the cell biology and trafficking of various components of this pathway, which led to our discovery that the transcription factors of the pathway (Gli1,2,3) accumulate at the tips of primary cilia (a sort of signaling antenna on the cell surface) upon stimulation by Hedgehog ligand. This naturally led to an interest in primary cilia, which have been implicated in several disparate diseases ("ciliopathies") and has become a pet project for postdoctoral students.
The best part about being a postdoc mentor is that it helps me to stay current in my area of interest outside of my pipeline projects and to learn new perspectives or techniques from my postdocs themselves, which are often very different than those of our regular team members. There are also no restraints on which direction the project takes, provided it leads to novel, publishable findings. It is also very rewarding to watch the postdocs develop into mature scientists during their stay here and to help them on their way to a stimulating career.
One of the good things about working at Genentech is that because we work so collaboratively such that experts in a particular technique perform those experiments (with the added bonus of having high confidence in the results), we have time to spend exploring new areas. Thus, my lab recently completely shifted focus from cancer to kidney disease. We are interested in a protein mutated in chronic kidney disease and have generated over 100 monoclonal antibodies to understand its localization, biological function, and role in disease.