A Conversation with Napoleone Ferrara
The Genentech Fellow discusses his life's work: from discovering the core angiogenic signaling molecule, vascular endothelial growth factor (VEGF), to creating anti-VEGF therapeutics for wet age-related macular degeneration and cancerous tumors.
NYAS: What motivated you to go into research?
Ferrara: I studied medicine in Catania, Italy, my hometown. Initially I thought that clinical medicine was very interesting, but I didn't have a firm direction. Then, I met a professor of pharmacology with an established research group. I joined this group as a medical student and that's what introduced me to research. It was thanks to my post-doctoral mentor at University of California, San Francisco, that I was able to further hone my research interests. Both of these people were very influential and inspirational factors.
NYAS: Broadly, how did you identify VEGF and identify its role?
Ferrara: I was interested in endocrinology and neuro-endocrinology. The pituitary is the master regulator of many key physiological processes. During my fellowship at UCSF, I stumbled on a population of pituitary cells without an established function. As part of my postdoctoral work, I tried to characterize these cells. I found that they released a factor that promotes angiogenesis. Over time I was able to isolate this molecule: I named it vascular endothelial growth factor (VEGF). After that, and through the work of a number of other labs, it became clear that VEGF is a very important signaling molecule.
NYAS: As your work progressed, what were your biggest challenges in translating your discoveries to the development of therapeutics?
Ferrara: We were very fortunate that we found the right target but the challenge was proving that. Initially there was a lot of controversy about angiogenesis. There was skepticism about VEGF's role in angiogenesis; people thought that maybe there were other molecules at work. We had to prove our findings through sound scientific methods.
NYAS: What factors have contributed to your success?
Ferrara: I have a medical background even though I have not been a practicing physician for a long time. Perhaps that medical background helped me to guide my research into an area that is therapeutically relevant. I was also just very fortunate that the VEGF molecule turned out to be so important. I also think being at Genentech for 22 years helped push my work along. I think it would have been difficult to do the same work in a different setting.
NYAS: You recently received the 2011 Dr. Paul Janssen Award for your breakthrough research on VEGF, and in 2010 you received the Lasker Award. What do these awards mean to you?
Ferrara: They express the fact that my peers, my colleagues, respect this work, so that means a lot to me personally. But the awards also reflect on the work that my group has done over the years. To me, these awards are really a stimulus to do more. I see them as motivation to do more and better research.
NYAS: What are your biggest research priorities right now?
Ferrara: We're trying to follow up on our work on VEGF. We want to know why, for example, not all tumors respond to VEGF inhibitors. We want to understand resistance. This will mean dissecting tumors to refine our understanding of angiogenesis. Regarding pro-angiogenic therapies, clinical studies thus far have been quite disappointing. It's very difficult to reconstruct complex vessels to positively impact circulation. It would be really wonderful if someone could figure out how to do that.
For more information on Ferrara's work, view the Academy eBriefing on Targeting Angiogenesis: The 2011 Dr. Paul Janssen Award Symposium.