BRIGHAM AND WOMEN’S HOSPITAL in Boston, MA United States
About Deepak Rao, MD, PhD
Career path
1. How did you first get involved in immunology?
I started in immunology as a PhD student at Yale. I was in the MD, PhD program and I decided to do a PhD in immunology because I thought it was a particularly dynamic field. It’s a relatively young field. For people that are interested in medicine, it’s a field that’s universally applicable. There’s no field of medicine where immunology isn’t relevant. For MD PhD students who don’t quite know what kind of doctor they would like to be, a dedicated study in immunology is going to be useful, regardless of whether you become a cardiologist or a rheumatologist or a surgeon, or in really any medical field.
2. Tell us about the research you’re most proud of.
I’ve been particularly excited and satisfied by the research that we’ve been doing in the past few years. We were trying to look in detail at the immune responses that are going on in our patients, who we see in clinic. I’m a rheumatologist. I see patients with autoimmune diseases. I’ve been frustrated with the idea that there are all of these patients that have a disease that’s driven by an inappropriate activation of the immune system, yet we have very few tools to try and measure the active immune response that’s going on in these patients that we see every day. So we’ve really been trying hard over the past few years to be able to collect samples from patients that we see in clinic and look at the immune response in detail using increasingly sophisticated techniques – high dimensional flow cytometry, mass cytometry, RNA sequencing, now increasingly single cell RNA sequencing – to define the cell types that are activated, the pathways that are activated. And then we bring that back at the patient level to understand in this patient that we see today, in that patient that we saw yesterday, what pathways are most activated. And then how can we use that to decide how to better treat individual patients?
3. What is the most important trait a researcher should possess and why?
I have two. One is the ability to think clearly along logical paths. So much of what we do is absorbing what others are observing, reading what’s in the literature and then trying to make reasonable connections, to connect the dots, to put pieces together. So being able to pull out key insights from different talks, different papers and then put them together, to come up with a reasonable hypothesis is a survival skill for researchers. And this one’s important. The other one I think is flexibility in your thinking. There are so many experiments that we do that we really care about. We’re really hoping for one result, and then you get the opposite or you get a negative result. It’s important to be able to be flexible, to realize that there may be some value in this negative result and that may make the next positive result more meaningful or more specific or more interesting. I try to maintain that flexibility and share that with the trainees, as they’re disappointed about the twists and turns of how experiments are going.
4. What is the biggest lesson you’ve learned?
I don’t think I’ve had that much time to look back just yet. At least, that’s the way I see it. But one of the important lessons that I’ve learned is that if you’re doing experiments that are important, if you’re doing work that’s important, other folks in the field and in other fields are going to try and replicate it. And if you’re reporting work, you should be doing it in a way where you’re confident that others who pick it up and think it’s interesting will be able to get the same results and reproduce the same observations. In the experiments that we do, I’m oftentimes sharing this perspective that, if somebody else in another lab, down the hall or in another building or in another institution is going to do the same experiment, would they get the same results? And if not, why? What are the weaknesses in this? How do we make it more robust?
5. What advice would you give to young researchers just starting out in the field?
There’s always a worry about picking the topic. What topic do you think is most interesting or most exciting, but really if we’re being fair, there are so many interesting things to work on in immunology that there isn’t a right decision on that one. There are too many interesting things going on. I think that the two things that have worked well for me –one was choosing an environment and, in particular, a mentor, in an environment that really fosters your growth and where you feel comfortable that it’s a rich learning opportunity. And the other is the chance to get involved with some new technologies or emerging technologies, ones that you think are exciting that you can point towards an interesting question. Those opportunities don’t always come along. They don’t come along every time that you need them, but the chance to pick up a new technology and play with it – try to take advantage of that early on in your training.
6. Describe your average workday.
That’s migrated, of course, over the past year, like it has for everybody, I’m sure. But I have two daughters, who are now eleven and seven, and they’ve basically been in virtual school almost the whole year. So we’ve adjusted our schedules to try and get up early in the morning and work for an hour or two before the family gets up. Then I do most of my work from home now. I have an office in the lab that I’ve given over to the postdocs to use as their space, when they’re in the lab. I try to stay out of the way and work from home. I have, of course, Zoom meetings and phone calls for much of the day.
I try and get into the lab just about every day to wander around and chat with people. When I’m in the lab, I think folks know that I’m there to visit and to troubleshoot or to strategize. I live only about a mile and a half from the hospital, so I ride my bike in. I can get there in ten minutes, head up the stairs, wander around, see what’s going on, bother people and see what they’re up to, and then get on my bike and head back home.
Work with FOCIS and FCE's
8. Switching gears, how did you first get involved with FOCIS?
I first got involved with FOCIS through my PhD mentor, Jordan Pober. He was heavily involved in FOCIS and when I was a PhD student, he encouraged us to attend the meetings. I went to a couple of them during my PhD and came to really appreciate and admire the leaders at the time: Gerry Nepom, David Hafler, Gary Fathman and their perspective, in terms of human immunology and studying disease in people, and that carried through. That really had a huge impact on my early career and research directions.
9. How do you think FOCIS has changed your world?
One of the important areas of influence for me in going to FOCIS meetings has been this really neat perspective of seeing people coming from different fields who were thinking about how to manipulate the immune system in opposite directions. In my PhD training, I worked on transplant rejection and I was thinking about how to suppress undesired immune responses directed against transplants. And now as a rheumatologist, I study autoimmunity and we’re thinking about how to suppress undesired immune responses against the self. But at the same time, when you go to the FOCIS meeting, you hear these perspectives, as well as the opposite, folks thinking about how to induce immune responses against tumors, how to induce immune responses against chronic infections, and many times we’re thinking about the same molecules, the same pathways, the same cell types, but with totally opposite goals. Having a meeting that brings people approaching these similar questions, but from opposite directions has been really informative. It highlights different cell types, highlights different pathways that maybe you hadn’t thought about in the same way, that you hadn’t quite gotten a foothold in your specific area yet, but brings that broader perspective.
10. If your colleague asked you why they should join FOCIS, what would you tell them?
I really encourage people to participate in FOCIS for exactly this idea – you see different perspectives that people are looking at to manipulate the immune system in different directions with different diseases in mind, but in the same place. The group itself in having an honest focus on human disease and an emphasis on trying to understand immune responses that go on in patients is real and valuable and unique. And for those of us who were thinking about a human translational immunology, FOCIS has become a center point. It’s a meeting that I go to every year and encourage people to attend.
11. Tell us about the research you’re doing.
I’m the director of the FCE at Brigham and Women’s Hospital. The hospital is a major research center in Boston with a lot of interest in immunology in many different areas. Represented amongst the group are investigators who are interested in transplant and transplant rejection. There is a large group that’s interested in immune disease as it affects the brain in diseases like multiple sclerosis. There’s a large allergy group interested in the pathology of what drives allergic responses. The division that I work in is Rheumatology, Inflammation, Immunity with a number of investigators who are studying the pathologic immune responses that go on in different autoimmune diseases, including rheumatoid arthritis, lupus, scleroderma. Amongst the broader community, it’s really a wide range of perspectives in terms of the different types of disease that the immune system can cause as well as a wide range of complimentary perspectives on how we can treat these diseases and potentially identify novel biomarkers and new therapeutic approaches.
12. What is the vision/your dream goal of your FCE? What are the specific goals as the FCE Director?
One of the areas that I’m most enthusiastic about is the ability to generate cellular biomarkers of autoimmune disease. As we’ve been assessing patients that have autoimmune conditions like multiple sclerosis or lupus or rheumatoid arthritis, we rely on a pretty limited set of tools that try and identify and diagnose the disease, then measure activation in those diseases. We, as immunologists, are developing an increasingly sophisticated understanding of the cell types that drive these diseases. And what I would really like to see happen in the next couple of years is for us to develop tests that can measure the activation of different cell types in the blood that we know are relevant in these diseases and to turn them into biomarkers of disease.
So, for example, we have a pretty clear assessment now of the T-cell and B-cell populations that are expanded in patients with lupus. They’ve come from many studies from many, many different groups, including ours. What I would really like to see happen is for us to be able to do the hard work, to turn some of these typical flow cytometry assessments that we use in the lab all the time into real clinically actionable biomarkers, tests that we can order, that we can generate on patients that we see in clinic, and then use that information to help us identify how active the immune response is in this patient. The patient feels okay, but their immune system is really ramped up, so I’m a little more worried about this patient. Or, the immune system looks pretty quiet, we’re okay, we’ll see the patient back in six months. I would really like to see us develop some of these real biologic biomarker tests out of the insights that are coming from immunology labs at the Brigham. This takes a sort of translational effort to connect with clinicians, to connect with pathology and lab medicine, to develop the test in a collaborative way. But I think we’re ready for this. I’d really like to see this happen.
13. What are your biggest challenges?
Human immunology is hard and it’s increasingly hard now with COVID and social distancing and the challenges in terms of doing clinically oriented research. But the major barrier here is that we have to be able to navigate the complicated infrastructure of clinical medicine. We need to be able to identify patients when they come to clinic, be able to enroll them in studies, collect samples, and do this in ways where we can accumulate both clinical data, as well as cellular immunology data and begin to put them together. We have much less control than when you compare this to experiments in mice, where you can define the timescale as you want in in vivo experiments that you can control – when you’re going to set up the experiments, when the results are going to come in. Trying to do human translation work, where we’re interacting with patients is much more complicated. It takes an infrastructure to be able to navigate it. You need research coordinators who are in the clinic or available to participate when the opportunity arises. And that part is complicated and hard. But this is where I think the largest gains will come.
14. Why did you apply to be an FCE?
I have been impressed with the work that goes on in FOCIS for many years and I think it’s important for us to be able to participate in that. There are efforts across the country and across the world, thinking about how we may better evaluate immune disease in patients with autoimmune inflammatory conditions. And I’m enthusiastic about the idea that our site at the Brigham can participate in and contribute. And we’d like to be part of the conversation and part of the effort to improve some of these technologies very broadly.
15. Those are all the questions I had. Is there anything else that you’d like to add or expand upon or go into some areas that I didn’t ask about?
I would just reiterate that FOCIS really plays a unique role in human immunology and the FOCIS meeting hits a sweet spot of being able to bring together world-class immunologists, many of the most prominent immunologists and leaders in the field and presents information in a format that’s approachable, comfortable and productive. It’s a reasonable sized meeting where you can interact with other folks who are attending and meet people that you admire as well as folks who might admire you and be able to think collaboratively about some of these important questions in human immunology. FOCIS really plays an important, unique role. And we’re grateful to be a part of it.
Thank you for the opportunity. It’s really been a pleasure.