What makes us humans lies in our genes. But even with all their power, they are remarkably vulnerable to errors.
But these potentially harmful errors are an opportunity for humankind to study and treat, as it has been for Dana-Farber’s physician-scientist Srinivas Viswanathan, MD, PhD.
“We have the ability to make an impact,” Viswanathan said. “There are so many unanswered questions in cancer biology still, especially in our understanding of rarer subtypes of kidney cancer.”
One of these subtypes — called translocation renal cell carcinoma (tRCC) — occurs when a gene quietly moves, fuses with another gene, and activates it. While considered rare, it may be more common than we think because of its difficulty in being diagnosed.
“In a lot of examples in medicine, even outside of oncology, studying rare diseases has given insight into pathways that end up being very important,” Viswanathan says.
Beginning a passion-fueled journey
It’s been a rewarding path for Viswanathan after discovering a passion for research and medicine at an early age.
“I went to a math and science high school where I was first exposed to lab research and medicine as separate careers and then, when I went to college, I had the opportunity to work in a lab led by a physician-scientist, with several physician-scientist lab members who I observed merging clinical care with research,” Viswanathan says. “That was a bit serendipitous but how I became interested in the idea of being a physician-scientist.”
Physician-scientists have the unique ability to take care of patients, learn from their diseases, and use that as inspiration for new research, which, in turn, offers insight that can make a greater impact in both fields.
“It’s a continuous cycle of working in the lab and translating it back to new, better therapies,” says Viswanathan.
After attending Harvard Medical School and completing a residency at Massachusetts General Hospital, Viswanathan began a fellowship at Dana-Farber in Hematology/Oncology in 2017 . This was accompanied by research training in the labs of two more physician-scientist mentors: George Daley, MD, PhD, professor of biological chemistry and molecular pharmacology and dean of Harvard Medical School, and Matthew Meyerson, MD, PhD, director of Dana-Farber’s Center for Cancer Genomics. Viswanathan’s oncologic subspecialty, genitourinary cancer — which includes cancers of the prostate, kidney, and bladder — offered a vast biology landscape that had unmet clinical needs.
Viswanathan continued this cycle of clinical and basic research after opening his own cancer genomics lab at Dana-Farber in 2019.
“In our lab, we seek to leverage genomic and functional genetic methods to dissect the molecular underpinnings and vulnerabilities of cancer and to translate that understanding into better therapies for patients,” says Viswanathan. “We are particularly interested in studying the pathways that underlie cancer initiation, progression, and drug resistance, with a focus on genitourinary cancers.”
Going onward and upward
With the commitment to developing new therapies in genitourinary cancers, Viswanathan is researching through a continuous loop of learning and doing — transferring the mentorship he received during his training to the next generation of trainees in his own lab. Many of these trainees bring ideas, offer perspectives and inject creativity into their research.
“It’s a stimulating balance of research, clinical medicine and teaching,” he adds, “Training the next generation of scientists is one of the greatest privileges.”
When Viswanathan and the lab began to dedicate a larger portion of their research to tRCC, there was very little known about the molecular basis for this cancer. He describes his work in three phases:
- Advance our molecular characterization of this cancer
- Pinpoint the molecular pathways driven by the defining translocation
- Develop mechanism-inspired therapies specific for tRCC.
Now, the team is approaching a point where their hypotheses, based on preclinical data, can begin to be translated clinically.
“For the first time, we now have at least a couple of active trials at Dana-Farber that are open to patients with tRCC. Even though they may not have been designed specifically for patients with tRCC, they are at least attacking molecular pathways that have some scientific rationale based on what we know about tRCC ,” Viswanathan says. “In the near future, I hope that we can move toward clinical trials that are even more closely tailored to the biology of tRCC.”
As these newer trials continue at Dana-Farber, Viswanathan lets his passion guide him in new directions that could ultimately unlock new and better therapies for tRCC and other genitourinary cancers.