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When Patient Care Sets Research Course

Five Questions with physician-scientist Srinivas Viswanathan on bridging clinic to lab.

Srinivas Viswanathan, MD, PhD, was a clinical fellow just a couple years into his physician-scientist training when he met two young patients who had a rare type of kidney cancer. The standard treatments didn’t work for them. As a clinician, he knew there was little he could do. As a scientist, he wanted to do better.

More than a decade later, Viswanathan’s lab at Dana-Farber Cancer Institute (DFCI) is focused largely on doing better. The clinical quandary turned into a research question that he’s been pursuing ever since, starting as a side project in his lab and now a major effort. The ultimate goal: informing the development of the kinds of therapeutics those young patients he met in fellowship training needed.

Viswanathan is now an assistant professor of medicine and attending medical oncologist in the Lank Center for Genitourinary Oncology at DFCI. We caught up with him to talk about life as a physician-scientist, his research, and how the Models of Disease Boot Camp he attended a decade ago influenced his career track at a critical transition point.

Why did you choose to take the MoD course back in 2014, on top of all the rigors of the physician-scientist’s training you were immersed in?

One challenge for physician-scientists is you’re constantly mode-switching between research and clinical care. There can be long periods of time when you’re deeply involved in one or the other. The time from when you finish graduate school to re-entering the lab as a postdoctoral fellow can be five or six years. That’s a generation of science, during which time a lot can happen.

One of the things that happened while I was in clinical medicine was the advancement of next-generation sequencing and the discovery of CRISPR. There were all of these new scientific technologies that I wasn’t keeping abreast of during my clinical training, despite having completed a PhD.

The Models of Disease course was particularly designed for physician-scientists who may have had this gap in their scientific exposure while in clinical training. For me, the course provided a broad survey of new techniques and technologies that had advanced in science over the past few years.

Thinking back to 10 years ago, did anything in particular stand out about the boot camp?

It was memorable in a few different ways. First, it brought together a cohort of other physician-scientists who had gone through the same thing as I had, but in different specialties. Everyone had this common issue of re-entering the lab or getting ready to re-enter the lab after several years of clinical training.

“The boot camp was instrumental in setting the direction of both my postdoctoral research and my ultimate research program.”

A number of us had trained together earlier and then gone into different clinical areas, and were coming together again in this course. So there was a sense of community.

The course was also designed well scientifically. It was not limited to one specialty and had applications across science. I think its focus on timely research advances was what we needed to get our feet wet in thinking about returning to the lab.

In the decade since that transition, you’ve built an integrative genomics lab applying these next-gen genomic sequencing technologies. What is your current focus?

My lab is focused on applying integrative genomic technologies to understand the biology of genitourinary (GU) cancers, especially cancers of the kidney and prostate. That was the focus of my clinical training in hematology and oncology, and I was looking to merge my clinical and research training to make advances in those cancers specifically.

In the lab, we try to identify new molecular targets for treating these cancers, especially those recalcitrant to current treatments. We use emerging genomic modalities, including DNA and RNA sequencing and CRISPR, to analyze and profile patient specimens at a large scale.

At the time I was re-entering lab work, these technologies were just emerging. The MoD course was probably my first real exposure to some of them at a high level. It described the current landscape in genomics and functional genetics and got me thinking about how they could be leveraged in my clinical specialty of oncology.

It would have been tough to dive into a new area without a survey course like that. In that sense, I’d say the boot camp was instrumental in setting the direction of both my postdoctoral research and my ultimate research program.

What drove you to want to be a physician-scientist and pursue this area of research?

I think physician-scientists are an endangered species, but play an important role in the biomedical ecosystem. You train as a physician to understand the clinically relevant conditions that need better treatments, and you train as a scientist to understand the approaches that could be used to discover that next generation of treatments. You kind of serve as a bridge to put those together.

Every physician-scientist lies on a spectrum between leaning more on the physician side or the scientist side. For most people who’ve been through this training, I think both are equally important parts of one’s identity, regardless of how you distribute your time.

For example, I was in clinic this morning. That gave me an opportunity to see patients with GU cancers. Then I came back to the lab this afternoon and asked: What are the important problems that can lead to better therapies for those patients?

We can collect specimens from patients and analyze the molecular profiles to try to understand more about the biology of their conditions. Then we can generate hypotheses and test them in the lab, with the goal of developing treatments that can be tested in clinical trials and contribute to improvements in patient care.

What’s the most rewarding part of being a physician-scientist?

“I think the most rewarding part is actually feeling like you’re using both sides of your training.”

I think the most rewarding part is actually feeling like you’re using both sides of your training. One of the cancers we study is a rare subtype of kidney cancer called translocation renal cell carcinoma. My interest in this subtype of kidney cancer was spurred by patients I had seen as a clinical fellow. Had I not been a trained clinician or had the opportunity to see those patients, I don’t think this would be a subject of research in our lab.

This interest started initially as a small project and has now turned into a major effort in the lab. We’re trying to understand the biology of this subtype of kidney cancer and identify new therapies for it, because existing therapies for kidney cancer are less effective in this type. So this represents a clinical need that has inspired a research question.

It’s rewarding to have that dual training impact my laboratory’s research program in that way. However, what would be even more rewarding is if ultimately this research leads to new clinical trials and eventually new and better therapies for patients with this type of kidney cancer.

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