susan-keown_
Susan Keown was a staff editor and writer at Fred Hutchinson Cancer Center from 2014-2022 who has written about health and research topics for a variety of research institutions. Find her on Twitter @sejkeown.
Dr. Supriya Kumar “Shoop” Saha lived only 40 years. But in his time on earth, he made an outsized impact on the science of the rare and deadly liver cancer he studied, and on the lives of those who loved him.
The physician-scientist beloved for his warm personality and well-known for his professional contributions died peacefully at home with family on May 6 of complications from a bone marrow transplant for the treatment of myelofibrosis, a blood disorder.
"He was a fantastic scientist, thoughtful, kind, soft-spoken and insightful,” said Fred Hutch Senior Vice President Dr. Eric Holland, who is director of Fred Hutchinson Cancer Research Center's Human Biology Division, where Saha was on the faculty. “We are all heartbroken and will miss him greatly. It is such a great loss for everyone. There are so many wonderful things he would have done had he still been with us.”
Saha was one of the only scientists in the world to have started a lab dedicated to cholangiocarcinoma, which originates in the bile ducts that carry a digestive fluid from the liver and gallbladder to the small intestine. While still rare, the disease is growing in incidence, Saha’s own research found. On average, patients survive just one year after diagnosis. Saha’s research helped to kick off the development of desperately needed new treatment strategies.
Dr. Andrew Zhu, Saha’s clinical mentor, said Saha’s soft voice and gentle demeanor complemented his intellectual firepower and clinical skills.
“Shoop was one of the few people whom I have met who was truly gifted both in the lab and in the clinic,” said Zhu, who is director emeritus of liver cancer research at Massachusetts General Hospital Cancer Center, where he worked with Saha. “In addition to being a rising star in basic and translational science, Shoop was also a passionate clinician with great clinical instinct and superb skills."
"He did so much in so little time,” said Dr. Eliezer Van Allen of the Dana-Farber Cancer Institute, who became fast friends with Saha when they did their medical fellowship together at the Boston cancer center. “The tragedy of all that is that he was just getting started.”
One of the most lasting impacts of his career, said Saha’s postdoctoral research mentor Dr. Nabeel Bardeesy, will come from a “critical mass” of other scientists his brilliance attracted to the study of a cancer that has long been under-researched.
“When a talented scientist goes into an area of research and makes exciting discoveries, that definitely has an impact on how a field is perceived,” said Bardeesy, a faculty member at Harvard Medical School. “I know people who have chosen their career goals based on research inspired by Shoop.”
Research sparked by a patient brings new hope
Saha joined the Fred Hutch faculty in 2016. Holland, the Fred Hutch division director, remembers being blown away by Saha’s “spectacular science” the first time he saw him present his work during a visit to the Hutch. When the division recruited its next group of new faculty, “he was top of our list,” Holland said.
Saha, who held both M.D. and Ph.D. degrees, was an assistant professor at Fred Hutch as well as a medical oncologist at UW Medicine and Seattle Cancer Care Alliance, where he specialized in caring for people with liver cancer.
Saha was born in Louisiana to a physician mother and biomedical engineer father. He grew up in South Carolina, where his career was inspired by his mother’s work at that time as a small-town doctor. She was "a way for me to see how much of a tremendous impact a physician could have on patients’ lives,” Saha said in a 2018 interview. “I wanted that for my own career.”
As a physician, Saha was known for his unassuming, humble demeanor that counterbalanced his intellectual brilliance. Hutch faculty colleague and friend Dr. Andrew Hsieh remembers when Saha arrived in Seattle, “He signed up for clinical duties right away," beyond what was required. Despite the heavy demands of starting up a new lab as an early-career scientist, he was eager to do patient care — it was “part of his blueprint,” Hsieh said.
In fact, it was a particular patient who inspired Saha's research path. The man had cholangiocarcinoma and was close to Saha in age. He had a mutation in the gene that codes for an enzyme called IDH1, whose activity is critical in fundamental cellular metabolism. But no one had ever mapped out how a mutation in the IDH1 gene upset those processes in a way to cause cancer.
Saha was determined to figure out this mystery. There was a great need to do so: There are no standard treatments for people with cholangiocarcinoma for whom surgery or chemotherapy fail — that is, the vast majority of patients with this cancer. Learning a cancer’s biology is a prerequisite for designing better ways to fight it.
Saha was aided on his quest, said research mentor Bardeesy, by his calm demeanor, which allowed him to look rationally even at problems he was personally invested in, and by an “unusual constitution” that enabled hard work for long hours.
"He’d send me an email considering a problem at 9 p.m.,” Bardeesy said. “And then he’d resolve it at 3 a.m., and then he’d be in the lab or writing emails at 8 a.m.”
The tools Saha created to find his answers are an important part of his legacy, Bardeesy said. Notably among these are strains of mice genetically engineered to bear particular cancer-causing mutations in IDH1 and other key genes. Such mouse models are important resources for scientists who want to understand what makes a cancer tick and how best to target it with treatment.
Saha “developed these essential resources where there were none previously, which took an enormous investment and no payoff at the time,” Bardeesy said. “It’s like starting a transportation company but you have to first build the road yourself — it’s only after a huge investment in effort and time that you can eventually benefit from your work. Moreover, the benefit from the effort extends far beyond what one gains oneself. Shoop took that endeavor on and we’re harnessing what he began to this day.”
Eventually, Saha’s hard work with his special mice and other tools revealed that the IDH1 mutation was causing cancer by interfering in the cell’s normal development — essentially causing the cells to persist in a stem cell-like state instead of developing into the specialized liver cells they were intended to be. This state put these cells on a hair trigger. Any nudge — such as exposure to a toxin or the presence of a mutation in another gene — could set them off into the uncontrolled multiplication that’s the hallmark of cancer.
And, Saha and others found, there were drugs that could intervene.
One week after Saha’s death, an international team of scientists, including Saha’s former mentor Zhu, published the results of a large, randomized Phase 3 clinical trial demonstrating that a new drug that blocks the mutant IDH1 enzyme helped slow cancer progression in patients with advanced cholangiocarcinoma who had the mutation.
Bardeesy and members of Saha’s team at Fred Hutch, like postdoctoral researcher Dr. Iris Luk, now are carrying out continued work delving into the results. They’re learning how the drug works — just as Saha’s lab research predicted, it turns out — and how, perhaps, to make it work better.
Luk remembers her last conversation with her mentor before his death. He said he really wanted the team to figure out the remaining details of how the IDH1 mutation causes cancer. And he believed in them to get it done.
“And that’s completely in line with my passion. I really want to know,” Luk said. “I’m going to commit myself, because of him, but also because of myself.”
Great mind, bigger heart
Before entering hospice care in April, Saha had spent nearly a year and a half in the hospital for graft-vs.-host disease, a complication of transplant in which transplanted donor immune cells attack the patient’s healthy cells. Throughout that difficult time, he continued his research from his hospital bed, analyzing and writing up data, reading new scientific studies in his field and mentoring his lab members.
“His brain was constantly thinking about this disease — not his disease, but the disease that he studied,” said Hsieh, who would "talk shop” with Saha on visits to his hospital room.
Why Saha’s continued devotion to his work, even in the midst of terrible illness? "One reason is his passion for science,” Luk explained. “Another reason, I think, is he wanted people in the lab to be taken care of; he didn’t want people to feel abandoned.”
Saha had been married since 2015 to Dr. Sita Kugel, a pancreatic cancer researcher and assistant professor in the Hutch’s Human Biology Division. The two met when they did their postdoctoral training in neighboring labs at Harvard; they joined the Hutch faculty at the same time.
The couple’s son, now 3, was born after their move to Seattle. Van Allen remembers flying out to visit the new family and proudly watching his friend be a father. “He would drop anything, at all times, to play. And because he was who he was, he had infinite patience,” Van Allen said. “Of course he did, because he was Shoop.”
That devotion to his family was what drove Saha’s decision to undergo the bone marrow transplant when his disease worsened, said postdoc Luk. As an oncologist, Saha knew well just how difficult the procedure could be.
“He told me it is terrifying,” Luk remembered. “And then he said, ‘But I still have to do that for my family.’ That was his high priority. If he had to climb Everest, he would do it.”
While Saha’s legacy to the world is his scientific contributions — the discoveries he made, plus the resources he created for others’ discoveries in the future — for those who loved him, his legacy is written on their hearts.
“I wish he could see how many people he touched,” Van Allen said. “Maybe he did see, before he passed.”
Saha is survived by Kugel and their son Jothin, his parents Subrata and Pamela Saha, his brother Sunil Saha, a niece and nephew, eight aunts and uncles, and 23 cousins.
A memorial for Saha will be held at a later date. Gifts in his memory to Fred Hutch will support the continuation of his research. The family is also requesting contributions in Saha’s memory for the education of his son. Checks can be mailed to: CollegeAmerica 529 savings plan, P.O. Box 6273, Indianapolis, IN 46206-6273. Checks should be payable to CollegeAmerica, with "4000935791 Sita Kugel Owner FBO Jothin Saha" on the check memo line.
Learn more about Saha in his obituary in The Seattle Times.
