Joan Massagué
Joan Massagué

Joan Massagué came to Memorial Sloan Kettering more than two decades ago and became captivated by his work in cell biology.

At Work: Cancer Biology and Genetics Program Chair Joan Massagué

When I was a student at the University of Barcelona in the 1970s, biochemistry was the area of study that provided the best venue for finding out how things work biologically. This was before there were separate programs for fields like cell biology and molecular biology. Biochemistry breaks down biological functions to their most elemental pieces — individual molecules — and then we can reconstruct how these molecules control the life of cells, and how cells constitute the tissues of a whole organism.

Even within the modest context of what the University of Barcelona had to offer then, there was plenty of opportunity for a young investigator like me to pursue scientific inquiry, apply myself to the discipline intellectually, and conduct experiments in the laboratory. Young scientists must understand that, most of the time, research is about frustration — not getting results fast enough or findings that are clear enough. But the small portion of the time when a discovery is made, the exhilaration that it produces makes it worth all the effort. If you can't live with that, you have to tell yourself, “This is not for me.

What I learned in graduate school — in addition to the science — was the ability to test myself in this area. And it gave me the confidence to say, “This is what I like, and I'm going to do more of it.” I chose to go to the United States for my postdoctoral fellowship [at Brown University], where there were more opportunities, more resources, and better scientific technology.

There was never a moment when I said, “I'm going to devote myself to research, and this is what I'm going to do with my life.” For me, making that decision was never a conscious act. I came to the United States because I would be able to refine my skills, but I always assumed that at the end of my postdoc, I would go back to Spain and enter the pharmaceutical industry.

At the end of my fellowship, however, I found myself with the opportunity to start my own laboratory and pursue my own projects. I was offered a position as an assistant professor at the University of Massachusetts Medical School. A starting professor has many episodes of panic about failure, about not getting grants and not getting the project to take off. I always had the attitude that if it doesn't work out, that's okay, because I'm going back to Spain anyway. I was and have always been very aggressive and deliberate in my research, but this attitude gave me a unique degree of freedom that I would not have otherwise had.

So I applied for National Institutes of Health grants, and I pursued research that might have been considered risky by some. And within three or four years, my project had really taken off. I had received the grants I needed, and I found myself in the midst of starting a project that turned out to be very relevant to cancer.

Basic research will always be the engine of the discoveries that drive more disease-oriented research.

Joan Massagué, Cancer Biology and Genetics Program Chair

My graduate training and postdoctoral work had been in the study of hormone action and how hormones affect the behavior of cells. The hormone I studied was insulin. After I had my own laboratory, I initiated studies on a then-obscure and mysterious set of factors that tumor cells secrete, which make normal cells behave as cancerous ones. I wanted to isolate these factors and figure out how cells recognize and respond to them, the same way they do to hormones. The factor that we purified became known as transforming growth factor-beta (TGF-ß). We now know that TGF-ß is the most important physiological inhibitor of cell growth, and when it is lost, cells lose their ability to stop growing and then die. But it also can turn from a tumor suppressor to an activator of tumor growth.

In 1987, I was approached by [the late] Ora Rosen [then a member of Sloan Kettering Institute's Molecular Biology Program, who was best known for cloning the gene for the human insulin receptor] about leading Sloan Kettering Institute's Cell Biology Program. She knew my name from the days I was researching diabetes and noticed that I had moved on and was publishing work related to cancer. So I came here and embraced the job. And at that point I said, “Well, I guess I'm not going back to Spain anytime soon, except on vacation.

For me there was a huge learning curve, both scientifically and administratively. I was made Program Chairman when I was only 36, and the challenge was enormous. The first few years were very tough. But at the same time my own research was advancing, the Cell Biology Program was beginning to grow and flourish. Many of the researchers I recruited during that time — with the help of [then-Memorial Sloan Kettering Cancer Center President] Paul Marks and other leaders in the institution — are now very important senior members of our research community.

There is a lot of extremely important basic science still to be done in the context of cell biology. Basic research will always be the engine of the discoveries that drive more disease-oriented research. But by the late 1990s, my laboratory was becoming much more focused on cancer-directed research, specifically the genes that cause breast cancer to spread to bones. When Memorial Sloan Kettering's Cancer Biology and Genetics Program was created last year, it seemed natural for me to go in that direction, because it was part of the continuum of what I was already doing.

The goal of the new program is to continue to develop research that focuses specifically on aspects of cancer. Much of the research is translational, and members collaborate frequently with clinicians. It is also focused on the genetic aspects of particular types of cancer, including those of the brain, breast, prostate, lung, and ovaries.

None of this would have been possible without the support of my wife. We met only a short time before we came to the United States. She also assumed that after a few years we would go back to Barcelona. But at the same time I was pursuing my career in science, she was pursuing hers in education — first in Massachusetts and then in New York. She is now a superintendent in the New York City public schools. It is remarkable that this other person had the same open mind about feeling comfortable and developing professionally in what was, in the beginning, a foreign country.