Spotlight with Jeff Bluestone, PhD

1. What attracted you to the field of immunology?
I was in graduate school as a master’s student at Rutgers University. I was working on virology, studying a small polio-like virus, mengovirus, trying to understand the molecular characteristics of the virus. It was a very restricted study, which, believe it or not, was limited to determining the number of adenines in the PolyA tail of mengovirus.

But one summer, I did an internship at Sloan Kettering Institute (SKI) in New York, and became very excited about the opportunity to use the immune system to attack cancer. SKI was embarking on some of the earliest cancer immunology efforts in the field. Dr. Bob Good, a pioneer in T cell and B cell biology, was running the institute, and had done some incredible work in Immune oncology. Although the systems were very complex, I was convinced that the immune system would have enormous impact, not only on cancer but on many other diseases. I decided to leave Rutgers and join the Sloan Kettering Division of Cornell Medical School to complete my PhD.

2. After you received your PhD in Immunology from Cornell University, how did you decide to do your postdoctoral fellowship at the National Cancer Institute at the NIH?
Although I very much enjoyed my research in cancer immunology at SKI, I found the field very complex and lacking important insights that could allow for in depth understanding of mechanism. We knew little about the molecular basis of cancer, the antigenic differences from normal cells and many insights that we now take for granted including genome sequencing, oncogenesis, and when and where tumors develop in humans was missing. Most importantly, we knew little about the tumor micro-environment and how it influenced immune response.

Therefore, I decided to step back to learn more about the fundamental principles of the immune system and how it recognizes/distinguishes foreign from self and maintains tolerance. I applied to a number of laboratories at the NIH, and ended up joining the lab of Dr. David Sachs, a leader in transplant immunology. It was a great way to start my independent career, concentrating on understanding the fundamentals of T cell recognition in a controlled environment -allotransplantation – where timing, pathways and underlying immune principles were more mature.

3. You worked at the NIH for six years before becoming an Associate Professor at the University of Chicago. What motivated you to make this move?
Like every young faculty member, I was very fortunate to have great mentorship and to learn a tremendous amount at the NIH – not just from David, but from many colleagues at the NIH. The NIH was an extraordinary institution in the 80’s, with great scientists across-the-board in immunology. However, the NIH had limited resources for growth. I’ll admit, I was ambitious and wanted to broaden my research, get back into cancer and autoimmunity and see if I could make a difference on a larger canvas with more mentoring of students, both grad students and post-docs.

The University of Chicago was such an opportunity. Dr. Frank Fitch, an incredible colleague and mentor, was building something special at the university. There was exceptional research through the biological sciences division and he and others were committed to building an enhanced immunology program. The University of Chicago had a fantastic cohort of scientists, so I had an opportunity to expand my thinking and expand my science.

In the first 5 years after my recruitment, we brought in incredible people like Dr. Craig Thompson, Dr. Jeff Leiden, and others. Moving to the Ben May Institute for Cancer Immunotherapy provided a fertile environment for me to get back into the cancer field both as a member and eventually as Director of the Ben May after Frank stepped down.

The move proved incredible for the lab research. We would able to make contributions into the discovery of early principles of T cell co-stimulation, the identification of CTLA-4 as a checkpoint regulator and the field of regulatory T cells. At the same time, the University allowed me to establish several translational programs including an Islet Transplant Center, and robust translational programs in organ transplantation and autoimmunity. Most importantly, I was fortunate to become the founding Director of the Immune Tolerance Network, an amazing organization, bridging the immune fields of Allergy & Asthma, Transplantation and Autoimmunity.

Finally, the time I spent as Executive Vice Chancellor and Provost (EVCP) at UCSF was truly an amazing experience. My boss, Chancellor Susan Desmond-Hellmann, had a great vision, leading the institution in ways that impacted science, translation and patient care. It was a difficult time in science with the NIH budget going down, with the recession, and all kinds of challenges to maintain a cutting edge infrastructure for scientists to conduct their research. I proud of the fact that over the five years that I was EVCP, we were able to maintain our #1 NIH rankings, build strong academic-industry partnership and increase philanthropic support, especially for our basic sciences building new programs in Precision Medicine and Stem Cell biology.

5. Do you miss anything from the earlier part of your career?
Like many scientists, as I became more senior and took on administrative roles, my direct connection to the research, working at the bench, was reduced. But fortunately, I was able to paint on a bigger canvas and help support others productive research programs. The founding of the ITN was a special time to work with exceptional people in partnership with NIAID. The NIH had never had that kind of partnership with academia.

If there’s one thing I’ve missed in my career, it’s that role of leading the ITN. It is surely one of my proudest achievements and continues today as a cutting edge clinical network that bring scientists together from all over the world to conduct innovative and creative clinical trials in immune-mediated diseases. The ITN has conducted multiple transformation studies that have changed our understanding and treatment of immune diseases, induced tolerance in several transplantation, autoimmunity and allergic settings, and, most importantly, branded the ITN as a place where you can do great fundamental research with human samples and clinical trials that inform basic mechanisms of disease.

The good news is that although I miss the ITN, having stepped down in 2010 when I became EVCP at UCSF, it remains a truly exceptional organization, representing the best that FOCIS aspires to with leadership from many FOCIS leaders including Dr. Jerry Nepom, the current ITN Director and Deputy Director, Dr. Larry Turka, who leads the mechanistic studies group.

6. Earlier this year, you were named the President and CEO of the Parker Institute for Cancer Immunotherapy. Tell us more about this breakthrough collaboration.
It should be clear from a lot of the things that I’ve already said, that what I love most is interrogating and applying the immune system to understand and treat disease. Being fortunate to combine a fundamental research lab with collaborative consortiums to work together in an effective and synergistic way is what keeps me engaged and excited about the future. I believe that the formula for advancing science requires great people, able to take risks, make big bets and combine interdisciplinary efforts to advance the field in an environment posed to break down barriers to collaboration and translational research. The Parker Institute for Cancer Immunotherapy represents all of that.

The Institute, now includes a consortium of six different institutions: MD Anderson, Sloan Kettering, UCSF, UCLA, Stanford University and Penn State; led by great scientists Dr. James P. Allison, Dr. Jeff Wolchok, Dr. Lewis Lanier, Dr. Toni Ribas, Dr. Crystal Mackall and Dr. Carl June, respectively, and now counts more that 60 labs, 400 investigators and an exceptional Parker Institute for Cancer Immunotherapy staff, among its constituents. Everyone in the Institute is committed to tackling the most challenging problems in cancer immunology. All six sites are working together with a common purpose of basic and translational science. Together, we have developed a strategic plan, a roadmap designed to identify critical areas of research. We have built a strong collaborative environment, a shared sandbox, by sharing ideas, discoveries and manuscripts before they’re published. We have created organizational efficiencies including the use of a single IRB, common procedures for sample and data collection and a collaborative and interactive ethos. The goal of the Institute is to make sure that the scientists aren’t bogged down spending half their time writing grants or progress reports, or filling out stacks of regulatory forms, and freeing them up to focus on their best science.

7. Looking back on your career, is there anything you would have done differently?
Oh no, I don’t regret anything that I’ve done. I’ve felt I’ve been very fortunate and lucky. I’ve been like a double-helix of DNA. I’ve been able to wind one strand of research throughout my career (that’s spanned all aspects of immunology) with a second strand of organizational focus to science, promote collaboration and build the infrastructure to facilitate structures where the whole is greater than the sum of the parts. This would not be possible if I was not so fortunate to benefit from so many great mentors, scientific colleagues and family that have helped me at every critical junction of my career.

8. Do you have any advice to share with someone starting out in the field?
There is no more exciting time in biological sciences than right now. Our ability to use some incredible tools to interrogate the immune system in humans is unprecedented in history. For young people, it’s a great time to study the immune system in humans. I encourage people to think about working across model systems and humans as they build their labs and their science programs. There’s so much we can learn by studying the immune system in humans and connecting it to the knowledge gained through basic research in animals.

It’s also a tremendous time for collaborative and interdisciplinary research. I would encourage any young person to collaborate and partner, and to be open with their research. We live in a time now where team research allows larger questions are being asked. Sitting silo-ized in your lab with a bench, a centrifuge and a desk is not the way the most innovative science is being done today. Collaborate with other people, work across disciplines and ask big questions because you can only benefit in your own work.

Finally, I would tell any young person that they shouldn’t get bogged down in the concerns about the academic ecosystem built on limiting resources and constraints like tenure. Good people continue to do well in the system. There are enough resources that if you focus on doing exceptional science, big problems, and risk taking early in your career, you will excel and anxiety and stress will not be overwhelming. Instead you’ll make a difference and change the world.