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Faces of Physician Scientists: Kathleen Sakamoto, MD
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Nancy J. Brown, MD

Interview on November 9, 2017

Tell me about yourself, your research, and how you started on the physician scientist path?

My research focuses on understanding the pathogenesis of leukemia and developing potentially novel therapies to treat children with leukemia. The other area of interest is bone marrow failure syndromes and studying signaling pathways.

My pathway to becoming a physician scientist is somewhat unconventional; I did not go through the usual M.D./Ph.D program like MSTP, and did not have a PhD prior to starting medical school. I went to medical school to become a doctor and during my clinical rotations I realized that I enjoyed pediatrics. I then completed a pediatric residency at Children’s Hospital of Los Angeles and decided to subspecialize in Pediatric Hematology-Oncology, which was very exciting because [in this field] you have continuity of care, bond with your patients and their families, and you feel like you can make an impact by doing research. There is the potential to give children, who would otherwise have a fatal disease, a chance for a cure.

Another aspect of my specialty field is that there are many opportunities for research, because cancer is complicated. There are many pediatric cancers that still need research to prevent the long-term toxicities of our patients.

Two of the three years of a Pediatric Hematology-Oncology Fellowship Program are dedicated to either basic laboratory, translational, or clinical research. Since I had some experience with basic laboratory research during my undergraduate education, at Williams College, I decided to focus my research training in the laboratory.

I had a tremendous mentor at UCLA, who had trained physician-scientists previously. It was a wonderful opportunity and [I was able to obtain] enough grants to remain at UCLA as a faculty member. I spent about four and a half years in the laboratory before I became a Principal Investigator of my own laboratory. At that point I didn’t know if I would be successful in academic medicine, but I [continued to] published papers and received grants during my fellowship training and as a junior faculty member. I remained a faculty member [at UCLA] for about 20 years, was promoted, and ultimately became the division chief of Pediatric Hematology/Oncology at UCLA. I moved to Stanford about 6 years ago as a Pediatric Hematologist Oncologist, and Division Chief, Fellowship Program Director and now am focusing on my research and mentoring students, residents, fellows, and junior faculty.

The most unconventional part of my career was, after I was promoted to Associate Professor at UCLA, I went on a sabbatical for a year at the California Institute of Techology, which was within driving distance of UCLA. I was able to extend my sabbatical year to do a PhD thesis in the same laboratory, and completed this after 3 years while I was a faculty member at UCLA, doing clinical service as an attending, and supervising my own lab (at UCLA). That was a pretty intense experience, but I was glad that I did it, and my mentor was very understanding of my other responsibilities. It was a tremendous experience and a stepping stone to advance my career. Although this was unconventional, I enjoy the variety of activities in my career such as being a clinician, researcher, and teaching. I am also director of a NIH T32 training program in Pediatric Nonmalignant Hematology and Stem Cell Biology. In this way, my career is always changing and never gets boring.

It sounds like you’ve had great mentors along the way. What are the traits or aspects that make a great mentor?

I had very little molecular biology experience when I joined my mentor, Judy Gasson’s, lab. She was a mentor who really looked out for my best interest, which is key, and someone who is always available and accessible to answer questions and advise.

The first thing my mentor told me when I joined her lab was, “you need to apply for these five grants.” I had never written a grant before but she challenged me to do it, and of course I did write them. We [sent the drafts] back and forth and I just continued to write them. In this business, our “bread and butter” is writing grants and papers; without these one cannot remain in academic medicine with a research career, and one cannot be promoted, tenured, or have job security. There are many potential road blocks but I knew from the beginning that I would have to continue to publish and write grants [to be successful]. Writing and speaking are key components to communicating our research to the scientific community. These were skills that I had to learn during my training because they are not necessarily taught in college or medical school.

Having an established mentor with a good track record of NIH funding and someone who has trained physician scientists successfully in the past as well as publishing really good papers are critical. So I had a perfect mentor who was willing to discuss experiments, look at my data, and help with grants and papers. Research can be very discouraging at times; compared to medicine, it’s very different. Research is slow, methodical, and takes time, while in medicine, there is more immediate gratification. The thing I enjoy most about research is that it is very creative and allows one to think outside the box and discover new things.

As a mentor myself, it is gratifying to see those I have trained to go on to become successful. A mentor is many things and being successful is about working incredibly hard, having the passion to do research, and being a little bit lucky so that your results can be published. Not all projects work out well and that’s part of mentorship also – [mentors] need to be on top of things so that if a particular project isn’t working they should advise [their mentee] to take a different course or different project, so that they are still successful and publish at the end of their training.

Describe a time when your research did not work as expected and took more time than expected? What advice can you give to individuals who have struggled with research?

Research is hard and experiments often do not work. When I was at Cal Tech I was trying to get an experiment to work and it took me over one year. It was discouraging [at times] but then all of a sudden the experiment would work and I could see progress. In science, we have to love the process of doing research because [in research], it’s not only about the endpoint. I have always liked doing experiments and working at the bench. If doing experiments is not enjoyable, being in the lab is not fun. It is frustrating when experiments don’t work, but if you enjoy problem solving then it becomes a challenge and gratifying when things work. Again, there is no guarantee that one will be successful in research, but all we can do is work hard and do the best we can.

One of the problems with being a physician scientist is that some may feel that they will always have their clinical practice to rely on if things don’t work out in the lab. There is job security as a physician and it is something to fall back on in case things do not work out in the lab or if someone decides not to continue to do research.

How much time do you spend between research and clinic?

I spent approximately 35-45% of my time seeing patients, the rest of the time is focused on research. I do a little bit of teaching and some administration. Approximately 50% of my time is dedicated to research, which is not ideal. As a junior investigator, it is critical to have 80-90% protected time.

Medical school and residency are busy times, how did you find time to stay involved in research during these times?

Being involved with research is helpful during medical school and residency, even if it means just going to lab meetings. Students and residents should try to find or identify an area of research they are potentially interested in, and decide whether would like to participate in clinical research or bench research. Once that decision is made, they should identify potential mentors, read up on their research [in the area that they are interested in], meet with the mentor, and spend time with the people in the research group, to get some exposure, and pick a project that they can work on, approximately 10 hours a week. Medical Students have done research as undergraduate students so they might have had some exposure to research, and may have already identified the areas they are interested in and potential research projects. It is important to focus on a project for a period of time; this is much more useful than going from one lab to the next.

When is it reasonable to start applying for grants? Is this something that should primarily be done during fellowship?

It depends on the type of grant. Some schools offer intramural grants for undergraduate or medical students. There are also external research grants for students, residents, and fellows. It is never too early to apply for grants. A lot of grant writing is just “practice makes perfect.” The earlier a person gets started in writing grants, the better.

What is the best type of training to initiate during med school/grad school that would best prepare trainees to become physician scientists (business training, financial training, leadership training, etc)?

It is helpful to know how to run a business, e.g. be PI of a lab. As part of our training program, we have workshops on campus for post-doctoral fellows to learn how to manage a lab. It’s important to know how to manage personnel, work within a budget, how to mentor, etc. Having a mentor who will help someone just starting up a lab, can be helpful. This is more important for fellows than, say a medical student, but some type of formal training in this area [is beneficial]. As a student, it’s more important to get your foundation in science, learn how to become a doctor, than to have this type of formal training, although it’s never too early to get exposure to this.

Is it more difficult for physician scientist to be involved in basic research? Is it easier to be involved in translational research? What is the role of physician scientists in basic research?

The role of the physician scientist is to be a bridge between the basic scientists with Ph.D. degrees. The definition of translational research has really changed. When I was a fellow we were trained to do very mechanistic-type research [that stemmed] from a hypothesis driven question with the hopes of finding some type of therapy for a disease. I think now the focus is more on the translation to clinic. It is challenging for the physician scientist to be involved in fundamental/basic research because they are competing with PhDs who have much more formal training in research. When I trained as a research fellow, I spent four and a half years in the lab – that’s compacting a standard eight-year graduate school plus postdoctoral fellowship training [in half the time] – I had to be productive at an accelerated rate to get to the place of being ready to become a PI.

PhD scientists often study normal physiology whereas physicians focus on disease-related research, since they learn about disease during medical school. Along those lines, I am studying leukemia, not normal blood cell development.

There are different ways for a physician scientist to do research; they can either collaborate with a basic researcher, they could help obtain samples for basic researchers, or they can conduct clinical trials where they are still doing a little bit of lab work analyzing samples. There is a whole spectrum of researchers that are MDs. I do think that this has changed through the years because in the past all the MD fellows were expected to go to the lab and learn basic research. Now it is much different; a lot of our MD fellows receive a Master’s Degree in Clinical Research, including Epidemiology, Translational Research. Some of the subspecialty fellowships, e.g. UCLA and Stanford, offer Ph.D. degree programs. Everyone should find their passion and focus on their specific research interests, which will lead to a successful academic career.