Dr. Ryan D. Roberts, MD, PhD is a physician for the Division of Hematology and Oncology at Nationwide Children’s Hospital, a principal investigator for the Center for Childhood Cancer at the Abigail Wexner Research Institute at Nationwide Children’s Hospital, and a member of the Translational Therapeutics research program at The James Comprehensive Cancer Center at The Ohio State University.
At the Roberts Lab, their primary focus is uncovering how osteosarcoma, a form of bone cancer, spreads to the lungs—the most common site of metastasis. By studying the molecular signals and interactions between cancer cells and the lung environment, the lab aims to identify new therapeutic strategies that could prevent metastasis and potentially save lives. Their cutting-edge research includes innovative cell culture systems, animal models, and advanced genomic techniques, pushing forward the boundaries of cancer treatment and offering hope for patients.
What inspired you to pursue a career as a pediatric oncology physician-scientist?
First and foremost—kids are so cool. They’re funny. They’re innocent. They’re supposed to be (and sometimes are) blessedly and adorably naïve. Teenagers are in this really interesting in-between state where they’re almost independent and perceive that they have this immense amount of wisdom, which is also adorable. It makes working with them and advocating for them so easy. Second, when choosing something that I would do for the rest of my life, I was looking for something that was meaningful enough that I would be inspired to fight through the tough times and scientifically fascinating enough that I would be challenged and intellectually engaged— thinking about the problems even when I wasn’t working and excited to go to work in the morning. Osteosarcoma fits that bill well. It’s a tough nut to crack but it will have a huge impact when we do.
The Roberts Lab at Nationwide focuses specifically on tumor-host interactions that occur in osteosarcoma pulmonary metastasis. How did you decide to focus on osteosarcoma, and this specific research area?
A long time ago, in a galaxy just across the street from where I work now, I had chosen Pediatric Oncology as my clinical focus and decided who I wanted to train with for my laboratory postdoc experience (Peter Houghton), but hadn’t settled in on a scientific problem that I could devote my life to. When I finally got to a scheduled break where I had some time to dig into the lab, I was anxious to get things going. I told Peter my ideas about what I intended to study (it wasn’t osteosarcoma). He told me that I was cute but naïve (a lot like a teenager, maybe?) and not thinking like a scientist. He sent me back to the drawing board—over and over and over. I was frustrated that I couldn’t find a question that was highly interesting, potentially impactful and that I was capable of answering (it seems so easy to do, but it’s not!). Then all fell together—I kept thinking about my patients with osteosarcoma and how the lung metastasis made all the difference, but we knew very little about why this bone tumor grew so easily in the lungs. If we could elucidate that biology, it would show the path to intervention, which could transform the care these patients receive and alter outcomes that have remained stubbornly unacceptable for decades. Peter agreed, and I’ve been focused on this question ever since.
What do you like most about the physician part of your job? What are the challenges?
As for challenges, cancer just sucks. While the good days are really, really good, the bad days can be really, really bad. It becomes easy to feel inadequate, even impotent, when I have nothing helpful to offer. And, some of the logistical necessities of providing care (insurance, paperwork, etc.) can grind on providers. That aside, there is a clear and direct sense of fulfillment that comes from being the person that someone needs during the most consequential moments of their lives. Giving families affected by childhood cancers the absolute best care available, helping them understand the potential implications of decisions and navigating their treatment journey, and being a partner with them as their lives change dramatically is a sacred privilege and an awesome responsibility.
What do you like most about the scientist part of your job? What are the challenges?
I love discovery. I love solving problems. I love sitting down at a computer, entering the last pieces of data into a spreadsheet (after months of work performing an experiment), and graphing the results. Every once in a while, I get to be the first person on earth who sees that our hunch was right and become the only person who knows something. I love that feeling. Now, far more often, I learn that our hunch was wrong, and we have to go back to the drawing board and figure out why. But, that just heightens the anticipation and makes the moments of discovery that much sweeter. The hard parts of being a scientist are maintaining positivity through all of the experiments that don’t “work” and maintaining funding. The latter is a challenge—running a lab is like running a non-profit business where funding will always end precipitously in 1-2 years. Working to push that cliff further and further away year after year often becomes the primary focus of an investigator.
What advice would you share with early-career investigators and physicians who are interested in focusing on rare pediatric cancers?
Only that it’s a great community to work with. People are here because something drives them to be here. It’s a small pond we swim in, but one where we can have an impact. These kids deserve our expert attention and have long deserved better options. We need to make that happen. If we can choose the right questions and dedicate ourselves to answering them, we can make a difference. And it will all be worth it.
The Roberts Lab utilizes single-cell transcriptomic analyses to study changes in gene expression that occur genome-wide within each of the different lung and tumor cell types and evaluate the importance of promising genes using virus-based systems that facilitate manipulation of gene expression. These types of analyses are possible due to major technological advances in the past few years. How have these new technology platforms changed the way your lab conducts research?
The technologies that I use on a daily basis regularly blow my mind. It’s like watching a jumbo jet fly—I know how it works and have seen it happen over and over again, but I still can’t believe that it’s even possible. I continue to stumble on new ways that we can use these technologies to answer questions that I wouldn’t have even considered answerable five years ago. I’ll be honest, it is fun. We now appreciate how tumors are complex organs created through the cooperative action of distinct subpopulations of cancer cells and the otherwise normal cells that the tumors have manipulated in ways that make them highly abnormal and the sometimes unusual ways that our treatments can affect each of these different cell populations within a metastasis—things that we didn’t even know we needed to think about when I was a fellow in training. These technologies have made my lab increasingly dependent on advanced computational approaches and we’ve had to adjust over time, but it has also opened doors and led to new approaches to osteosarcoma, even suggesting treatments that we never would have thought about previously.
Where do you see the greatest potential for advancement in osteosarcoma research in the next five years and what are you most excited about?
I’ll be honest, I’m pretty optimistic about where things are and where they are going right now. The community of scientists and advocates is strong and growing. The pace and quality of science from investigators focused on the disease is ever increasing. Our clinical trialists used to be limited by a relatively small number of good ideas that were out there. Today, the good ideas are outstripping our ability to test them. Some of these are going to work—I have faith. They won’t all work, because they never do, but we have become significantly more sophisticated about how we develop these ideas and far more rigorous in the way that we test ideas before they ever get to patients. This does stack the odds a little more in our favor. We have to do the work. We have to have the funding to do the work. It will be hard and probably messy because that is the nature of science, but I am very optimistic that we will make it better—make it objectively better—for young people diagnosed with osteosarcoma before I retire.
