FOCIS President (2016-2018)
A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology and is the Director of the Hormone Research Institute in the Diabetes Center at the University of California- San Francisco.
Dr. Bluestone’s research over the past 25 years has focused on understanding the basic processes that control T cell activation and immune tolerance in autoimmunity and organ transplantation.
To introduce our membership to Dr. Jeffrey Bluestone, we interviewed him about his career path and his work with FOCIS.
Read the transcript below or listen to the audio.
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.
4. In 2000, you moved from the Midwest to the West Coast, to become the A.W. and Mary Margaret Clausen Distinguished Professor of Metabolism and Endocrinology; and Director, UCSF Diabetes Center. What are some of your proudest moments since you’ve been at University of California, San Francisco (UCSF)?
My time at UCSF has been some of the best times in my career. I’ve been very lucky. I’ve worked with some incredible people doing incredible science. UCSF is a special institution founded on principles of great basic science and tremendous innovation. UCSF sits in the center of the Bay Area, the home for entrepreneurism and new technology. The students, the faculty and the many cutting-edge companies constitute an amazing ecosystem for discovery.
I am most proud of the continued research my students have embarked on at UCSF. I hope we have had an impact in areas such as Treg biology and therapeutic application. I am most proud of the fact that many of my students have gone on to independent impactful careers in both academia and industry. But I also, have gained great satisfaction from the opportunities I have had in administration. Often a dirty word, administration leadership has given me an opportunity to be as creative and innovative as my science. One example – when the stimulus package was created by the Obama administration to grow us out of the great recession, I was asked to coordinate the UCSF effort to apply for those funds to support “shovel-ready” programs. There was a lot of money but little coordination. I am proud that I was able to help organize folks around this opportunity. We were able to maximize access to the NIH and NSF funds and effectively use the money to advance exciting science throughout the institution.
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.
It started when Sean Parker and I had met over six years ago to discuss Cancer Immunotherapy. He had, through his own insightful thinking and some personal experiences, begun to appreciate the value the power of the immune system and envision, and before many others, the potential of immunotherapy in the treatment of cancer. This was before the first approved checkpoint inhibitor, anti-CTLA-4, was approved in 2011 or the use of adoptive T cell therapy more broadly to treat blood cancers like ALL and CLL.
Sean told Susan Desmond-Hellmann and myself that he wanted to create a new multicenter Institute that would drive cancer immunology discovery and drug development. Given my background, I immediately had an affinity for this, having trained in cancer immunology, and having worked in immunology and cancer over the years. And, unlike 1980, the timing was right to create this innovative institute to perform great science, collaborate like hell and break down the barriers that have stifled recent scientific advances including lack of resources, technologies and regulatory barriers. Sean provided $250 million to start the effort and invited me to become the founding CEO and President in April of 2015. For me, the Parker Institute represents a coalescence of a lot of experiences during my career: the science, the collaborative environment, the reduction in bureaucracy, and an ability to accelerate science, discovery, and drug development for patients
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.
1. How did you first get involved with FOCIS?
I was involved from the very beginning. Dr. David Hafler and Dr. Garry Fathman were friends of mine, colleagues, people who I interacted with quite a bit in the Immune Tolerance Network (ITN) (remembering that the ITN started in 1999/2000). They were at the 1st meeting of the ITN and some of the first discussions we had were about how to broadly take immunology as a discipline and expand it across a wide variety of research areas. When they started FOCIS, which was truly an incredibly insightful process of a coalescence of ideas, they did a great thing. They asked me to include the ITN, so we were a partner organization from the very beginning. For me, personally, I took a seat on the FOCIS Board and took on the role as head of the FOCIS Centers of Excellence (FCE) at UCSF. Very early on, I had a deep commitment to FOCIS.
2. How has FOCIS changed your world?
It bleeds into my world more than it changes it. It’s been an incredibly important organization for the community – from the meeting, which has a really, truly interactive and broad impact on people from a variety of different areas of immunology, to the FOCIS Centers of Excellence (FCEs), to the education courses. FOCIS has woven into many aspects of what I care a lot about. It’s hard for me to say it’s something that’s changed my life, but it’s been a really important outlet for a lot of the things I care a lot and help spread throughout the community. It’s important to me because it really is another arm for distribution of some of the core ethos that I’ve maintained in my career – concepts of great science, collaboration, and efficiency. FOCIS is a reflection of things I care about most. Hopefully the best opportunities for FOCIS are ahead of us. Over the next couple of years, it will be exciting to see FOCIS expand some of the great things it’s doing already and implement new things.
3. What are your goals as the FOCIS President?
One of the advantages that I have as FOCIS President is coming into an incredibly strong organization that has great history, great people who have been involved over the years, a lineage of fantastic scientists, clinicians, and leadership. So, in that sense, it starts from a very strong place, which is great.
What I’d love to see in the next couple of years is that the core values of FOCIS, the interdisciplinary model and collaborations efforts across the societies continue to grow and touch more people. Specifically, to touch young scientists in a more effective way, so that they can participate in what I think is the most exciting field of science that exists (the immune system). I also hope we can create partnerships that will expand the reach of FOCIS to more places, both in academia and in industry. We live in a very exciting time, not just because the science is so great, and the opportunity to make a difference in people’s lives is so great, but also because the lines between different constituencies in our culture (for-profit, non-profit and industry, academia, industry) are blurring. Some of the best scientists – like the FOCIS Past President, Dr. Frank Nestle, and others have moved to industry. One of my greatest desires is to figure out ways to bring these communities even closer together because of the assets that each of them brings to the table.
Another thing which continues to be important is education. We take a field like cancer immunotherapy and you can see the explosion of what happens when we have some successes in that field. And in my own work starting 20 years ago on immune checkpoints, who would have known that some of the most exciting areas of clinical impact in melanoma and lung cancer, and other cancers would have started? How do we actually continue to grow that interdisciplinary collaboration? Through education! I think FOCIS is the right place, at the right time to bridge the educational gaps. Whether it’s in transplant or cancer or asthma and allergy, to really bring together different people in different disciplines. I hope we can continue to all our venues – the meeting, the courses, the FCE’s, to bring an interdisciplinary effort to use immunology as not just a tool to fend off disease, but as a therapy to treat disease.
Finally, the distribution of information is key to advancing the field. You can do all the science you want but if you don’t get the information out to the community, then they won’t take advantage of it. One of the things that I’m already very proud of (that we’ve set up in the last year) was the relationship with the new journal, Science Immunology. We participate actively on their boards, provide free subscriptions to our members and help to publicize the best science in human immunology research. This is just one example of the value of the FOCIS brand and how FOCIS can be of tremendous value to the community. Most recently, I helped teach the first FOCIS European Advanced Course in Immunology in Paris, France. Dr. Terri Laufer, Dr. Abul Abbas and Dr. Ignacio Anegon did an outstanding job as they have will all our courses helping educate and excite the young investigators in the field. I hope there are more activities like these to come!
In that regard, I believe our FCEs are a largely untapped resource for the clinical immunology community. I am excited to work the various FCE Directors, Dr. Megan Levings and Dr. Tim Niewold, to increase the visibility and programmatic success of these centers, worldwide. Sometimes we don’t appreciate the international nature of FOCIS. Our European members and FCEs are an extraordinary asset that I hope to continue to support. If we can help to advance the field through our FCE’s in a collaborative way to promote everything from standardization of aspects of clinical investigation to collaborative efforts for new clinical trials, that would be icing on the cake.
4. If your colleague asked you “Why should I join FOCIS”, what would you tell them?
FOCIS is the home for translational immunology. A place for immunologists across the translational and disciplinary spectrum to find access to a community of scientists, a community of clinicians, and a community of scholars who have broad interest in the field. Immunology is in itself a core organ in the body that impacts so many different aspects of health and disease. Having an organization whose sole purpose is to bring together these communities is a unique opportunity.
I would ask anyone interested in Immunology: why wouldn’t you want to be in a room listening to one talk that is in your field and then someone whose work is orthogonal to your own but with a common set of understanding of the immune system. Talks given by the very people who have described and applied the most fundamental mechanisms and aspects of disease in their field. Talks, and potential collaborations in academia and industry that could easily impact what you’re trying to accomplish in your field? Why wouldn’t you want to be associated with scientists who have broad and deep understandings of the fundamentals of the immune system that can impact your patients or your science, or your students’ science? Why wouldn’t you want to be a part of an organization that is focused on the thing you care most about – which is – how do we understand and utilize the immune system to basically treat human health and disease?
For me, FOCIS really is unifying the field of translational immunology, the ultimate Precision Medicine. It’s where you can dissect the fundamental underlying mechanisms of disease that impacts multiple diseases and can determine with precision the personalized medicine we will be to advance cures. Where the science will tell us why type 1 diabetes is more similar to rheumatoid arthritis than it is to type 2 diabetes. So instead of studying symptoms, we’re studying mechanisms. FOCIS is a great place to think about mechanisms of disease.
