The Journal of Young Investigators

Dr. Sandra Ruscetti is the head of the Retroviral Molecular Pathogenesis Sections for the Laboratory of Cancer Prevention at the National Institute of Cancer (NCI) in Frederick, Maryland. I had the opportunity to interview Dr. Ruscetti about her research and the outlook of preventative research. Dr. Ruscetti shared some of her predictions for the future of her work, as well as some advice for future graduates who are looking to pursue a career in science. She received her Ph.D. from the University of Pittsburgh, where she studied the genetic control of the immune response. In 1975, she began working at NCI and is now a senior investigator and head of her section.

Trista Haupt: Could you give me a brief explanation of your research? I am not familiar with leukemia research using retrovirus-based mouse model systems.

Dr. Ruscetti: For many years my laboratory has used mouse retroviruses to understand the molecular basis for various diseases. Our focus has been on retroviruses that cause leukemia in mice and our goal is to obtain basic information on how molecular changes induced by the virus in blood cells results in the various stages of leukemia. Using the Friend spleen focus-forming virus, which was discovered by Charlotte Friend in 1957 and causes erythroleukemia in mice, we showed that the envelope protein encoded by the virus interacts with a receptor tyrosine kinase in erythroid cells, resulting in proliferation of these cells in the absence of their normal regulator erythropoietin. This causes the uncontrolled growth of erythroid precursor cells in the spleen, analogous to the initial hyperplasia that occurs in human leukemias. Because the erythroid cells can still differentiate into mature red blood cells, they are not yet malignant. However, some of these cells acquire a genetic mutation due to integration of the viral genome into the mouse DNA and this causes their transformation by blocking the erythroid precursor cells from differentiating, analogous to blast crisis in human leukemia. The transformed cells metastasize to the bone marrow, where they grow to such high numbers that they break through the bones of the skull and vertebrae to invade the central nervous system, causing paralysis. This is very similar to meningeal leukemia in humans, a frequent complication of childhood leukemia. By understanding the molecular changes that result in each stage of this retrovirus-induced leukemia and developing drugs to block or counteract these changes, we hope to better understand and treat human leukemias.

TH: Did you foresee yourself entering this career pathway early on or did you decide to enter this career while working on your Ph.D.?

Dr. R: Although I developed an interest in cancer research as an undergraduate and always hoped to have a career in that area, I did not carry out cancer research in graduate school. I studied the genetic control of the immune response in rats and in doing so gained a solid background in immunology and animal genetics which was beneficial to me in my later cancer research studies. After receiving my Ph.D., I applied for postdoctoral fellow positions in both immunology and cancer research labs. At the time, retroviruses were a hot area of cancer research, so I joined a lab at the NCI that was part of the Virus Cancer Research Program and began working on retroviruses that cause leukemia in cats. I had planned to stay at the NCI for only 3 years, the typical time to do a postdoc, but the research was so interesting that I jumped at the chance to take a Senior Staff Fellow position, which was the equivalent of a tenure-track position at universities. I received a tenured position eight years after originally coming to the NIH.

TH: What do you recommend for students who are thinking about going on to receive their graduate degree or Ph.D.? What options should they consider when deciding? I know cost is always a major concern for college students - do you feel that it is worth the financial burden to continue education right after receiving an undergraduate degree?

Dr. R: If a student is interested in having some input into a scientific research project beyond routine technical manipulations, it is almost always necessary to get an advanced degree. And the higher that you go, the more control you will have over the research that you carry out. When I entered graduate school, I knew that I wanted to get my Ph.D., so I chose a program that went directly to that degree. It took 6 years, during which I was supported by an NIH Training Grant to the University, but I was able to move directly to a postdoc position and start my career. I personally think that it is worth the financial burden to continue education right after receiving an undergraduate degree. Granted, that will have to be an individual decision.

TH: Do you have any encouraging words for students who are thinking about going on for their Ph.D. in science?

Dr. R: For me, a career in science has been wonderful. I enjoy the freedom of developing theories and planning experiments to learn important information that may help mankind. I love the camaraderie of the lab and being able to sit around over coffee discussing science, politics or the day’s news. It’s clearly not a routine 9-5 job and it’s never boring. A career in scientific research is like taking a class in college but never having the final exam. There’s always new information to be learned and the results of one experiment can lead to an entirely different approach. While it can be frustrating when the experiments don’t go right, the euphoria resulting from a great result makes up for everything! So I would encourage any student who would like to solve the mysteries of life to consider going on for their Ph.D. It’s worth the time and effort and who knows- you may end up winning the Nobel Prize for your important discoveries!

TH: What do you predict for the future of your research?

Dr. R: I hope that my basic research using animal models will provide clues to molecular changes that occur in blood cells that result in the development of the various stages of leukemia. I predict future research will be directed towards applying this information to detecting and treating similar diseases in humans.

TH: As you know in the past years, the number of students graduating in science-based fields has declined. Do you think that it is because of a lack of knowledge on the students behalf as to their awareness of scientific opportunities or do you feel that students are just moving away from science majors because they tend to be more difficult? It seems like there will be a lack of qualified people to replace current researchers in the future.

Dr. R: There has been a lot of effort to promote science-based careers in this country. We at the NCI participate in elementary outreach programs and high school internship programs to not only get young people excited about science but also to give them hands-on experience with scientific research. So students should be aware of scientific opportunities from an early age. What may be discouraging them from entering a science-based field, besides the fact that the science majors tend to be more challenging academically, is the long commitment, both in time and money that they must make before they have a “real” job with a good salary and benefits. Although it was 14 years after I received my B.S. before I had a tenured position at the NIH, during which time my salary went from bare minimum to decent, I never felt discouraged because I knew that I would eventually have a well-paying job that I loved. I think that the key to getting young people to embark on a career in science is to get them “hooked” by giving them the experience of working in a research environment. If they love it, they’ll stick with it for the long haul. Although, like you, I often worry that there may not be enough young scientists to replace all of the baby boomers who will be retiring within the next 10 years, I am encouraged by the efforts being made by various organizations to promote scientific careers and to help young people with the financial burden that training for these careers often entails.

TH: What do you think is the best way to boost the future of science?

Dr. R: I think that the key to boosting the future of science it to get students interested in science at an early age. For those students who clearly have interest and abilities in science, it is vital to provide encouragement, through mentors, and financial help before we lose them to other fields.

TH: You must be so dedicated to your research at NCI. Does your family share similar interests in your career field?

Dr. R: Like me, my husband has a Ph.D. in biomedical sciences (we met in graduate school) and runs his own lab at the NCI. Our research interests overlap (he works with human retroviruses that cause leukemia) and we’re always talking about science (our own and others) at home. Our love of science has rubbed off on our son (our only child), who will be starting his 3rd year at the University of Virginia majoring in biology and philosophy. He has worked several summers in research labs and hopes to eventually get his Ph.D. in one of the biomedical sciences.

     In the path towards a research career a student may face the daunting task of overcoming many hurdles such as time commitment for education and financial burdens. However, we can appreciate the rewards that such a career may bring for those that are passionate about contributing to our scientific knowledge, as we can see in Dr. Ruscetti’s case where her diligence has put her in the forefront of cancer prevention.