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Topics: Clinical & Translational Research, Education & Training, Five Questions

Preventing Lung Disease in Long-Term Rheumatoid Arthritis

Five Questions with physician-scientist Gregory McDermott.

As a medical student contemplating his career direction, Gregory McDermott, MD, was torn between his love of academic research and his desire to care for patients. During his rheumatology rotation in residency, he saw the opportunity to foster deep long-term relationships with patients and apply the learnings of basic science to patient care. He was hooked.

Now, as a young investigator, he’s trying to solve an increasingly vexing issue in rheumatoid arthritis (RA), the most common rheumatologic condition: How to prevent lung disease. It might seem an odd question for a condition known for joint problems. But that is the nature of RA today, where lung disease has become an increasingly important problem despite the development of successful treatments that control joint inflammation in the disease.

McDermott is an instructor in medicine (rheumatology) and an attending rheumatologist at Brigham and Women’s Hospital (BWH). He was a 2021 trainee in the Harvard Catalyst Clinical and Translational Research Academy (C/T RA), a two-year mentored program for young investigators pursing careers in translational science.

Your C/T Research Academy project is focused on identifying risk factors for serious lung disease associated with rheumatoid arthritis. How does this work exemplify translational research?

Over the last 25 years or so, a number of different medications have become available to help manage rheumatoid arthritis. These have helped reduce long-term complications such as debilitating joint damage, but lung disease remains an important one. Up to 10% of RA patients will develop what we call clinically apparent interstitial lung disease (ILD), which includes inflammation and fibrosis of the lungs. In screening studies, up to half or more people with RA have some kind of abnormality in their lungs. Interestingly, its prevalence may be increasing, and we’re not really sure why.

“Up to 10% of RA patients will develop what we call clinically apparent interstitial lung disease (ILD), which includes inflammation and fibrosis of the lungs. In screening studies, up to half or more people with RA have some kind of abnormality in their lungs.”

My research tries to identify and understand risk factors–genetic as well as clinical and demographic–for developing these complications. Are there signatures early in the disease course that might predict disease progression? The goal is to be able to risk-stratify people at the beginning of the disease. From there, we can ask a number of questions. Are certain treatments better for some people in helping to prevent or reduce the risk of lung disease? Are there other modifiable risk factors, such as smoking, where behavioral modification might help minimize risk?

The discovery of important genetic risk factors for ILD has opened the door to translational research, and we want to bring those discoveries closer to the clinic. New tools in immunobiology enable us to look at RNA profiles of different inflammatory cells in the blood. As those tools improve and we learn more about these signatures, hopefully we can use them to help identify patients who might, for example, respond well to a particular treatment, or who might be at high risk for a particular complication and require more frequent screening. Those applications are on the horizon.

How did you get involved in this research?

I always knew I wanted to do academic medicine and be involved in research. I loved the immunology and inflammation section of medical school, but it wasn’t until my second-year rheumatology rotation that I had a chance to see how rheumatologists were applying that knowledge. They were talking about the many pathways of these targeted medications that I had learned about in medical school.

I also really enjoyed the chance to develop strong longitudinal relationships with patients. In rheumatology, you don’t just see them once and never again. You get to know them over the years, when they’re struggling with their disease and, hopefully, when they’ve been treated and feel better.

I was really fortunate to get plugged in with some very helpful mentors during my residency at Massachusetts General Hospital (MGH) and here at BWH. I had a little experience in genetic research in oncology and cardiology, and knew I wanted to apply that to rheumatology. It felt like a natural fit.

You’re a 2021 enrollee in the Clinical/Translational Research Academy. What has been its value for you?

The C/T Research Academy has helped me in two main ways. It provided me with some of the tools an early-stage clinical translational researcher needs, including the nuts and bolts of how to design and conduct studies. The biostatistics course, for example, was fantastic for learning how to decide which test to use and how to implement it, understanding the software, learning the coding, being able to understand the limitations of the testing and the inherent assumptions you may be making, and helping grasp the epidemiologic tools. The genetics course with Benjamin Raby, MD, was also excellent. He helped us understand the methods, limitations, and pitfalls in designing genetic studies.

The other key aspect is support for career development, especially the chance to participate in mock study sections where we were reviewing and discussing other people’s grants. To sit in that reviewer’s chair and understand what the reviewer might be looking for was really eye opening, and has certainly helped me with my grant writing. Identifying the weaknesses in the grant writing process and how to address them up front has been helpful. We also learned how to convey both the excitement for the research project and feasibility at the same time. That’s really important in the early career stages, because you want a proposal that funders will be excited about but isn’t so ambitious they will say you can never accomplish it. You need to find that sweet spot.

“[C/T Research Academy] provided me with some of the tools an early-stage clinical translational researcher needs, including the nuts and bolts of how to design and conduct studies.”

The camaraderie of being in the group was also fantastic, especially the opportunity to go through it with people who are all in a similar career phase, working in various domains of medicine at different institutions. It was great to have a stable cohort of people that you got to know over the course of two years, to hear about their research, their successes, the challenges they’re facing, and what resources they’ve found to help advance their career.

Where are you with your career track?

I finished my fellowship at the end of June 2023 and started as new faculty at BWH in the section of clinical sciences, which is the clinical research section in the division of rheumatology.

I was recently awarded a two-year scientist development grant from the Rheumatology Research Foundation. I’ll be applying for a K award next. Thankfully, the current funding gives me some runway in which to work. We are fortunate to have that resource in our field.

Under the new grant, I’ll continue working directly with Jeffrey Sparks, MD, who was my main mentor during the C/T academy. The project extends our search for genetic risk factors in RA-related lung disease and asks whether viral infections are a risk factor.

Your rheumatology fellowship at BWH was book-ended by the birth of your first son, now three, at the start and a second son, born in April, at the end. As a young investigator and young father, how do you find work-life balance?

I don’t have an easy answer. I don’t know if anybody does. I would say that I’m still trying to find work-life balance. With just one child, I used to be able to get some work done after bedtime. But with two who are not on the same schedule, it can definitely be more challenging. Like anything else, it’s a matter of setting priorities. I try to really focus on the kids when I’m home with them and not multitask. I try to keep in mind what’s important, both at home and for my research.

One of the challenges of research is that there’s always more you could do, right? More papers to read, more projects to start, more grants to write. I’m trying to find the right balance between not stretching myself too thin, to still have bandwidth for work and family. It seems to be a continuous work in progress. I’m sure there’ll be ebbs and flows as my kids change.

I’m lucky because there are a couple of people in my division who have navigated this themselves. Hearing about any pitfalls to avoid or things that have been helpful has been key. I’m also fortunate to have an incredibly supportive spouse who’s in clinical research herself as a psychiatrist at MGH. Being on the same path has been an advantage because we’re able to understand what we are each going through and how the stresses of the job change over time. If there’s a really challenging period for one of us, the other can pick up the slack knowing that it’s going to be temporary.

We’re also very lucky that our four-month-old is a really good sleeper.

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