Max Jan and Ryan Corces-Zimmerman owe their friendship to the worms.
Corces-Zimmerman, now a second-year Ph.D student in Stanford’s cancer biology program, laughs as he recalls the Princeton biology lab where he and Jan met as undergraduates. The two young scientists spent hours poking the thousands of short-lived, millimeter-long worms that served as subjects in an aging study.
When a worm failed to react to their touch, they pronounced it dead and noted its age. Over many late nights in the lab, slowly tallying the thousands of live worms and dead worms, they accumulated a sufficient dataset to estimate a worm’s average life span.
Today, Jan and Corces-Zimmerman can point to that monotonous exercise as the first in a series of successful and increasingly creative joint efforts. During their six combined years at Stanford, they have spearheaded innovative research on the role of stem cells in cancer progression and relapse. Colleagues and advisors at the Stanford Institute for Stem Cell Biology and Regenerative Medicine say that Jan and Corces-Zimmerman’s work could fundamentally impact diagnosis and treatment methods for leukemia and other cancers.
And after years of prodding worms, Corces-Zimmerman says he’s embraced his Stanford research as an opportunity to engage in science that has direct relevance for human patients – science that makes clear a clear contribution to the advancement of medicine.
Jan’s soft voice takes on a professional edge as he discusses their collaborative research. By isolating and analyzing blood stem cells from several leukemia patients, he and Corces-Zimmerman are working to understand how stem cell mutations drive the progression of the disease. “It has a huge implication for what we do in treatment,” says Corces-Zimmerman. “If we don’t get rid of these cells that have these mutations, they’re going to cause cancer again.”
The project relies heavily on recent advances in human genomics, since genetic changes in the diseased stem cells must be compared to standard benchmarks in the typical human genome. Jan describes his work as a “nice little encapsulation of why the human genome project matters.” It’s an example, he says, of a real return on investment for millions of dollars in scientific research.
Given his upbringing, Jan’s awareness of that broader scientific context is no surprise. Both he and Corces-Zimmerman come from research science families. As a teenager, Corces-Zimmerman spent 12-hour summer days in his father’s biology lab.
“I would pass out on the way to work,” he recalls. “But I enjoyed the exploration of something, trying to find something new.”
Jan, whose parents are well-regarded neuroscientists, initially refused to rely on family connections. He found a summer job at See’s Candies in San Francisco – only to have his initiative thwarted by his peanut allergy. His parents helped him find a last-minute lab position, and he realized he had a future in medical research.
Jan completed his undergraduate work at Princeton in 2007 and enrolled at Stanford that fall. A class taught by Dr. Irving Weissman, Director of the Institute for Stem Cell Biology and Regenerative Medicine, sparked his interest in stem cell research. Jan joined Weissman’s lab, where he began studying leukemia stem cells under post-doctoral student Ravindra Majeti.
“He knows what it takes to succeed,” Majeti said of Jan. Now a faculty member, Majeti oversees Jan and nearly a dozen other graduate students conducting leukemia research. Among those students is Corces-Zimmerman, who arrived on campus in 2009. He jokes that he followed Jan.
“It worked out in undergrad,” he says, laughing. “So I figured, why not keep this whole thing going?”
Corces-Zimmerman pursued a position in Majeti’s lab on Jan’s recommendation. He liked the idea of working under “a young P.I. [Principle Investigator] who has a lot of time for one-on-one interaction,” and Majeti fit that description perfectly. And Corces-Zimmerman, according to Majeti, “asked really great questions. That’s how you can tell whether someone’s intelligent or not, what kind of questions they ask.”
From the beginning, both students saw exciting potential in Majeti’s area of research. Leukemia, Jan explains, is the best understood of human cancers, and the easiest to study because mutations in leukemic cells involve relatively dramatic, visible genetic changes. Their current project, though, has surpassed their expectations of success. “It’s going super fast,” Jan says. After less than a year, the students already have results from their first patient analysis.
Dr. Mark Chao, a medical student who also studied cancer biology under Weissman and Majeti, believes Jan and Corces-Zimmerman’s research will significantly enhance scientists’ understanding of cancer development. And both Majeti and Chao agree with Corces-Zimmerman that the project’s has tremendous potential to improve treatment methods, particularly in the area of relapse prevention.
Majeti attributes their rapid progress in part to Jan and Corces-Zimmerman’s close friendship. “It’s not a project that one person can do alone,” he said. “The fact that they have such a good personal relationship is critical, I think, to the success of the project – that neither one of them is trying to cordon off an area. It’s very important.”
The successful collaboration has positioned Jan to complete his Ph.D this summer, after just four years in the program. He will enter medical school at UCSF in the fall and ultimately plans to divide his time between medical research and practice. He also hopes to work overseas in global health during his remaining years as a student.
Although he jokes about following Jan once again, Corces-Zimmerman wants to remain in academia. “I love to teach,” he says. “So that’s my long-term goal — to finish my Ph.D, do a post-doc, be on the academia track.”
If that doesn’t work out, though, he still intends to pursue scientific research, perhaps through a job in industry. Laughing again, he recounts plans for a cloning enterprise that he and Jan hatched during a late night in their Princeton lab. “We wrote it out on paper,” he recalls, “thinking, ‘This is such a great idea!’ And then we walked into lab the next day and realized – there’s no way that would work! And then we just sat down again and started counting worms.”
Jan joins in the laughter. “Our next scheme,” he adds, “is going to work, though.”
Some would say it already has. “I see very, very bright futures for both of them,” Majeti says. He sometimes feels he’s learned more from these two young students than they have from him. With that recommendation, Jan and Corces-Zimmerman probably don’t need to worry about counting any more worms.