Curious Life Of Juan-Manuel Schvartzman

One thing becomes clear about Juan-Manuel Schvartzman when reading his lab's webpage: Schvartzman is curious.

Like many Columbia researchers, Schvartzman ("Juanma" to his friends and colleagues), maintains a website detailing his studies, publications, postdocs, and students. But Schvartzman's site is also like a portal into his scientific psyche, replete with his ruminations on, work-life balance, mentorship, and-possibly his favorite topic-curiosity-driven research.

"Ask interesting questions," is the first aim listed on the site's list of lab goals.

"Many of our questions stem from pure curiosity about how biological systems are wired," says Schvartzman, who joined the Vagelos College of Physicians and Surgeons in 2022 as assistant professor of medicine.

"But answering basic questions about cells also offers clues for treating cancer and other pathological processes," says Schvartzman, who treats patients with gastrointestinal cancers when he's not in the lab. "Because ultimately, cancer cells use the toolkit present in all cells to invade, proliferate, and metastasize."

Cells are what they eat

Today, most questions asked in Schvartzman's lab have to do with cellular metabolism-that is, what a cell eats and what it does with the byproducts (metabolites).

By altering metabolites and metabolic enzymes, it may be possible to force cancer cells into a less malignant destiny.

When Schvartzman started this line of research during his postdoc, he confesses he didn't know much about metabolism. "I still had this idea…that the wiring diagrams were essentially the same in all cells," he recently told Molecular Cell, and that metabolic reactions exist simply to maximize energy generation for cell activities or for growth.

A newer idea that metabolism not only fuels cells but can change cell fate-that cells "are what they eat"-fascinated Schvartzman as a scientist and as an oncologist. By altering metabolites and metabolic enzymes, he says, it may be possible to force cancer cells into a less malignant destiny.

Control with chromatin

In his own lab at Columbia, Schvartzman studies how metabolism influences cell fate via the cell's chromatin, an amalgam of proteins that compress DNA so it can fit within the cell nucleus. (Given his affinity for chromatin, a wonder of structure and function, it's no surprise that Schvartzman says he would have become an architect had he not gone into research).

It's now known that metabolites influence the deposition and removal of chromatin modifications, which affect gene expression and program how a cell adapts to its environment. "Metabolites can influence whether a cell remains more or less static, or rapidly divides and proliferates, the hallmark of cancer," says Schvartzman.

Schvartzman has found that polyamines, common metabolites in the nucleus, appear to play a key role, increasing a cell's susceptibility to be reprogrammed into cancer when levels are high.

Such findings suggest that it may be possible to change the fate of cancer cells by targeting metabolic enzymes. The field has focused on targeting transcription factors to reprogram cancer cells, but that concept remains technically challenging.

"Enzymes, on the other hand, are readily druggable, they're easy to modulate with therapeutic compounds," says Schvartzman, whose polyamine studies are funded by the NIH.

Lab life

The metabolism field is still in its infancy. And though he's only just getting started, Schvartzman has ideas about running his lab that are remarkably developed.

One of the first things he did after arriving at Columbia was publish on his lab's website a list of core values-everything from keeping lab notebooks to maximizing well-being to diversity.

Schvartzman's ideals are perhaps not so different from his research peers. What's unusual is how open he is about the human side of science. "Science is hard," he says. "You face adversity constantly, and you have to figure out how to overcome it." Sometimes, a break is needed to sort things out, and "great ideas may come from NOT doing science," he says.

Communication-with other scientists as well as with the lay community-is another of his touchstones: "We strive to be storytellers, and to learn from good storytellers," he says. He encourages all his lab members to talk to everyone about their science and always ask questions. As he told a recent interviewer: "Just like my kids who are constantly asking "why?" we should be doing the same."

Juan-Manuel Schvartzman, MBBCh, PhD, is assistant professor of medicine at Columbia University Vagelos College of Physicians and Surgeons, a member of the Herbert Irving Comprehensive Cancer Center, and assistant attending in hematology/oncology at NewYork-Presbyterian.