FOCIS Centers of Excellence Director
Vanderbilt Center for Immunobiology
About Jeffrey C. Rathmell, PhD
Career path
1. How did you first get involved in immunology?
I did undergraduate work at the University of Northern Iowa where they had a general biology college major. I also had chemistry and physics minors. I liked biology and biochemistry, but the exposure to research there was pretty limited. That’s been growing over time, but back then, there were just a few labs, so I did summer internships. I applied widely and ended up one summer at Rutgers doing some microbial biochemistry. The next summer I was at Jackson Labs where I was partnered with an immunology group to work on Lupus, actually dealing with the mechanisms of auto-antibody production and cell death. I didn’t know anything about immunology going into that, but I just had a wonderful time. It was a great internship, great summer and I learned a lot. I really became fascinated with the field. Then I went back to college for my senior year at Northern Iowa. There was no course in immunology, but I went ahead and applied to an immunology PhD program because I decided that’s what I wanted to do. I ended up at the immunology program at Stanford and it was a great fit. I’ve enjoyed it ever since. But it was completely happenstance that I ended up in that specific immunology internship.
2. Tell us about the research you’re most proud of.
The work that I’m most proud of in terms of defining a single paper or manuscript, that’s difficult. I think the bigger thing is the growth of the field of immunometabolism. During my post-doctorate and early in my faculty career, we were involved with cancer metabolism, which doesn’t necessarily have an immunological component and we were interested in cell metabolism in general. A lot of our research was done in leukemic and lymphoid cell lines. Some of the controls were just normal T-cells that we would activate, and the projects very easily transitioned to how normal T-cells regulate their metabolism. When we first started presenting posters, there was very little interest. I remember the first time I presented a poster on the subject, it was at a meeting of about 500 people. I had only one person stop at my poster. Now there are multiple meetings and hundreds of people attending the meetings. It intersects with cancer biology in the field of cancer immunotherapy and tumor microenvironment, so we’ve come full circle and it’s really rewarding to see that. It’s not just my lab of course, there have been other labs that have made important contributions. We were there early along with a small number of others and it’s really been fun to watch the field grow to what it is today. Seeing that field emerge and feeling like I had a role in its early phase is rewarding.
3. What is the most important trait a researcher should possess and why?
Resilience and persistence. You have to be curious and you have to be very smart. Those are essential. There are a lot of smart people, though. When you go to a meeting, there’s always somebody smarter than you in the room. You have to assume that. The most important characteristic is to recognize what’s interesting and to be able to deal with the adversity. Because when you first start, things may not work, and you have to be able to dig through all the noise to try to see why you think it’s important and then just keep fighting for it. When we were first starting in the field of immunometabolism and the field was not catching on, I knew it was going to be important. It just took a little while for it to get there. You see that on a more granular level day-to-day in terms of submitting papers and grants. There’s always peer review, sometimes kind and sometimes not, but you just have to keep your focus.
4. What is the biggest lesson you’ve learned?
The biggest lesson is that my natural inclination, particularly when I started my lab, is to try to do everything ourselves. There’s something to be said for that, but it’s a self-limiting approach because you can’t do it all. The technologies and the interdisciplinary nature of everything are so complicated now that you really don’t have any choice but to involve teams and get different groups of people involved. It’s more fun that way too. You don’t have to feel like you have to do everything. You also get lots of different opinions, different thoughts and it’s a better way to be innovative, with more minds throwing out ideas. You have different skill sets and that’s really valuable because you can’t learn all of the skill sets and innovation benefits tremendously from having multiple voices in the room.
5. What advice would you give to young researchers just starting out in the field?
The key thing and one of the challenges that you have is there are always lots of very good ideas that become interesting, shiny objects. The more senior you are, you have a little more leeway in terms of being distracted by the shiny objects and having more opportunity to play around in different directions. But as a junior person, it’s really important to have a focus. It doesn’t have to be just one thing, but it can’t be too many. You need to be known for something, but you don’t have to be known for everything. It takes a lot of discipline because there are too many things that sound exciting and you have to have the discipline to say this is something important, this is something I want to focus on. Strategizing around what not to do is very difficult, but can be the most impactful for success.
6. What is your average workday like?
Well, there’s isn’t such a thing. With COVID-19, everything’s been thrown up in the air, working from home largely. Lots of Zoom meetings. During non-COVID days, the average workday is usually to go into work with my wife, who is also a physician-scientist, and try to meet for lunch when we can. Oftentimes, that’s difficult to work out. There are a lot of meetings, a lot of student thesis committees, and lots of interactions around different groups. One of the side effects of involving different groups in your research is you have many more meetings and calls to try to keep up with everybody and what’s going on. Most of the rest of each day I’m running around talking to people in the lab and going to seminars. In the morning, I get up early and work at home from 6:00 am to 7:00 am or until 8:00 am and then go into work. And then in the evening, I try to catch up on emails, so that’s a typical day. Normally, I do a fair bit of traveling as well. I’m on the road more than I should be. It’s kind of a nice break from all that and I’m staying home at the moment with COVID lockdown. Still, I find that the travel is a good thing in the sense of getting out and seeing and talking to different people and presenting what we’re doing and learning a lot about what’s going on. The networking and the feedback that you get from that is invaluable.
7. Who do you most admire and why?
I’ve been on a little bit of a kick lately with the 50th anniversary of the Apollo moon landing, Apollo 11, in 1969. Of course, right now this is the 50th anniversary of Apollo 13, in 1970. I’m 50 myself and I’ve been following that. I’m really impressed with the whole program, first the astronauts themselves; they put their lives on the line. They didn’t really know if those rockets were going to work. I’m also impressed with all the scientists behind the scenes. There are some great movies out lately, for example, Hidden Figures. A lot of diverse people were involved: people behind the scenes, the science and the engineering involved. That blows my mind to think of the kind of limitations they had in computing power, but they still were able to work as a team to do that. That’s pretty cool. The space program really advanced science and engineering and everyone acknowledges how really important that was. I think though that things like the Human Genome project deserve the same kind of credit. Nobody put their lives on that line for that, so it’s different, but in terms of all the things that have come out– the increased ability to sequence and understand the genome and all of the genetics analyses we can do are truly amazing. You think about COVID-19, it was sequenced and tests came out way, way quicker than we could have done otherwise. So that’s a direct benefit of the human genome project that I think is also really impressive.
Work with FOCIS and FCE's
8. Switching gears, how did you first get involved with FOCIS?
I was familiar with FOCIS, from the meetings side, for a long time. I’ve gone to AAI, coming up through my own training and then I went to a FOCIS meeting and gave a presentation. I really liked it. It was a nice-sized meeting. All of the talks were relevant for basic immunology and the translational angle at the same time. It just seemed like the direction that the organization was going in was well-aligned with a lot of my interests. After that, I followed the organization and went to a couple of meetings, but when I started at Vanderbilt in 2015 to direct the Center for Immunobiology I didn’t know a whole lot about the Centers of Excellence through FOCIS. Once I learned more about them, that they were out there, I was surprised to learn that Vanderbilt didn’t actually have one. So, then it became pretty important to me to see if we could get ourselves associated with the organization. I connected with Jonathan Maltzman, who is an old friend that I knew was involved in FOCIS, and he pointed me in the right direction.
9. How has FOCIS changed your world?
I think that FOCIS does a good job of encouraging collaboration, allowing you to meet and interact with different sorts of groups. You know we’re a relatively new Center of Excellence. I’ve actually been to only one of the FOCIS Centers of Excellence meetings. But I was very impressed, obviously, with the breadth and the diversity of interests. We’ve already sent some of our student trainee representatives to the Advanced Course in Basic and Clinical Immunology, so that’s a very good opportunity for them to get exposure, learn some of the basic principles, and do it in a way where the students can interact with a lot of great teachers and leaders in the field.
10. If your colleague asked you why they should join FOCIS, what would you tell them?
I would say the organization strikes a nice balance between understanding basic mechanisms, but also how they apply to human disease. If you’re interested in translational work, either the bench all the way to the bedside, FOCIS covers it all and helps bring it under one umbrella.
11. Tell us about the research you’re doing.
We have a couple of projects that the Vanderbilt FCE is emphasizing. The main one is a group here at Vanderbilt that we’ve collectively termed the Human Immunology Discovery Initiative. The goal of this group is to try to approach human immunological diseases with new technologies to understand them at a cellular and genetic level using detailed cell phenotypes. We have a big push with the pediatric immunology clinic where we’re looking at patients with rare immunologic genetic disorders trying to analyze these specific mutations. We’re not necessarily focused on identifying new mutations and new diseases. We have pretty poor understanding of human immunology overall, relative to what we know about mouse immunology, for certain. One of the ways I think that we can get to that is by focusing on these rare diseases that have severe phenotypes downstream of a loss of function of single genes. If we can do a really detailed analysis of how that single gene affects the overall immune response, the overall immune status, we can learn an awful lot. That complements the approaches that have been taken looking at adult diseases that are more complicated and are often driven by smaller effects of multiple genes. We are looking at some of the adult populations as well, including rheumatology, where we’re applying the same technologies to bring high resolution cellular phenotyping as well as some genetic analysis. We also started working with other groups like the Vanderbilt Vaccine Center and another new group interested in immune-related toxicities of immunotherapies.
12. What is your vision/dream goal of your FCE?
I think that we can make some big advances. The main goal would be to use genetic approaches to better understand human immunology. I think that these rare genetic disorders are an invaluable tool to get there. Many of the genes that we know alter human immunity are these primary immune deficiency genes. We know how many work in mouse, but we don’t really know how they work in human. What I would really hope is that we’ll learn how they work in human to point to new drug targets and therapies, that will help not just those rare patients, but would also apply to more common diseases. Also, many of these pediatric patients have unknown disorders and we hope to identify new genetic causes for those diseases as well. The big goal is to be able to take these rare patients and see how they can inform us about human immunology and how it applies to the more frequent diseases. We have some deliverables that we’re trying to hit in terms of patients that we’re analyzing and the analytic approaches that we’re trying to bring to bear. In terms of specific timelines, we have a five-year plan in mind and I’m hoping that at the end of the five years we’ll have quite a better idea of how these rare patients can inform us about these diseases.
13. What are the specific goals as the FCE Director?
My specific goals again, they’re not really for myself, they’re largely about building research platforms that will have their own value. In addition to that, we’re bringing in students, post-docs and junior faculty to be involved with these projects. A big reward is when what we’re building becomes really valuable for their own research and helps them to reach their next career stage and gives them what they need to achieve other goals. The secondary goal would be to have the FOCIS Center of Excellence help catalyze more team science and more team grants and opportunities.
14. What are your biggest challenges?
One of the big challenges is that there are a lot of data, the data integration challenge. We need to definitely beef up our computational analytics ability, especially as you deal with these rare patients and try to bring them to the larger population. The other challenge is that we’re trying to integrate a variety of new and different technologies. We have to try to understand the strengths and weaknesses of each. I think we’ve got a reasonable handle on it for our current stage, but it is an ongoing challenge.
15. Why did you apply to be an FCE?
To be honest, because I was very surprised that Vanderbilt wasn’t one. Vanderbilt is, I think right now, number eleven in the country for NIH dollars. Our Department of Medicine is number two in the nation for NIH dollars. We have been one of the key sites for the Clinical and Translational Science Awards (CTSA) and one of the big strengths of the institution is the interaction between the clinic and the basic research, translational research. So Vanderbilt has a strong basis in translational work that is well aligned with what FOCIS is about. Plus, we do have projects that are specific and highly relevant for FOCIS. With the combination of the specific projects and the overall institutional culture, I just thought a Vanderbilt FCE was a great opportunity. We would be able to see how other institutions are managing a lot of these same challenges in terms of data management, data analysis, and how to integrate these new technologies. It seemed like this was something we should do and we’re happy to have the chance to learn from having these interactions with other FCE’s.
16. Talk about what’s come out of the BioVU research where you have compiled over 250,000 patient records.
We have not directly made that, that’s been preexisting. Vanderbilt was one of the early institutions to start an in-house DNA repository. There are around 250,000 records that have been genotyped or sequenced. What happens is that every time a patient comes to the hospital or clinics at Vanderbilt, they are consented to share left-over blood from their routine laboratory studies that will go into this resource. The real power is that the medical health record is associated with that DNA. This is a resource that all investigators at Vanderbilt can use to try to look at how different medical record codes and diseases are associated with different genotypes and genes. That’s been really a valuable tool. The fact that we have that in-house and we’re one of the early institutions to do this, was one of the drivers for us to say that we really need to focus on immunogenetics. We think about the opportunities in the immunological space and we have this really great genetic resource where we can look at what genes are associated with specific clinical codes. We have a great opportunity to try to build basic immune mechanisms back out of that.
17. What is the progress you’ve made on defining the entire human immunome using this information?
The director of the Vanderbilt Vaccine Center, James Crowe, has really been a leader in this area. He’s part of the Human Vaccine project and he’s doing a lot trying to develop antibodies against the COVID-19 virus, etc. What’s really interesting is that you’ve got the human genome, that includes all your genes, and the immunome, which is the genetic basis for your immunological repertoire and has an enormous diversity. This is part of the genome that is not captured in things like BioVU, because BioVU records your standard genes that are invariable. But your immunoglobulin genes, for example, are incredibly variable so that normal genome diversity is amplified by the incredible diversity of the immunome. That’s a whole different level of genotype information. This is what the Vaccine Center has been building on and trying to understand. When we think about our rare patients, we have an opportunity to say well, here’s a patient who has a very specific genotype that alters their immunologic function in some way that we don’t exactly understand. Now we can work with the Vaccine Center and say we understand their baseline genotype and also the entire immunological repertoire as well.
18. Talk more about the finding that there’s a ‘high frequency of shared immunoglobulin sequences among individuals in their responses to the Ebola and the Zika viruses. How has this impacted treatment?
I don’t know that it has impacted treatment directly, but it is surprising finding how much shared sequence and how much shared repertoire there is between individuals. This is from Dr. Crowe’s group and the Vaccine Center where they sequenced the complete immunoglobulin repertoire and the T-cell repertoire and found a very surprisingly high degree of shared sequence. If you do all the statistical modeling, it’s not by chance. There’s some selection for some shared components that we don’t understand. This finding underscores how much work we have to do to understand the human immune system and immune response across human disease.
Personal
19. What motivates you to work hard?
I guess I’ve always been a bit driven, but I like what we do. I like working with the students, in particular. I like seeing a project come together. Even when you’re a kid in school and you write a term paper, it’s rewarding when you get it done. It’s the same with any scientific paper or project. You have to put your head down and do the hard work, but the final result is very rewarding. There’s always something next to do to keep it going. Once you get a little further in your career, it’s not necessarily about your career anymore, it’s about other people. I’m not too worried about things happening to me. I’ll manage. But the main goal now is to help the students, the post-docs and the junior faculty, help them understand and move forward with what they need to do to hit their own career goals.
20. What is your favorite time management tool?
It’s important to serially uni-task. There’s many, many things to do and multi-tasking, trying to do all of them at once, I’m not very good at. So, I try to focus on one thing at a time and then move from one thing to the next.
21. What is your favorite vacation spot?
We have a vacation home just outside the Great Smoky Mountain National Park, so we like to go there. It’s a drivable distance from Nashville, so we get there usually, once or twice a month.
22. What is your favorite beverage or drink?
I probably drink too much Coke Zero.
23. Describe your hobbies. What do you do when you’re not working?
I like to run. I’m not a fast runner, but I try to be persistent and I run marathons. I started running half-marathons in graduate school, completing about one or two. Then when I was in my late thirties, I decided to start running marathons. I’ve run nineteen marathons so far. I was never fast but as I get older, it becomes less and less about the speed. I don’t run every day. It depends on when I’m training for something. If I have an event coming up, then I’ll try to run five or six days a week, but usually it’s more like three or so.