After her uncle was diagnosed with a type of kidney cancer called renal cell carcinoma around 2003, Humsa Venkatesh, then in high school, watched a team of oncologists struggle to battle the disease. “I think that was a very pivotal moment of my life,” she tells The Scientist. “Despite the fact that there was so much research being done, there were not a lot of new therapies that could be offered.”
Venkatesh’s uncle ultimately passed away, but the experience shaped her career, sparking an interest in translational medicine. She flip-flopped between pursuing academia or medicine as an undergraduate at the University of California, Berkeley, but the four years she spent working alongside biochemist Jennifer Doudna helped her chart her course. She came to think of medicine as exploring what is known, and research as exploring what is not. “I was much more interested in the unknown, and advancing that somehow to get more new therapies,” Venkatesh says.
She began a PhD in cancer biology at Stanford Medicine in 2013, just as next-generation sequencing technology started to take off. Suddenly, research into genetic and epigenetic factors driving malignancies dominated the field; Venkatesh focused on the tumor microenvironment. To her, targeting genetic abnormalities that only distinguish a portion of the malignant cells in a heterogeneous tumor is like trying to kill a tree by plucking individual leaves. Disrupting the microenvironment, however, is akin to uprooting the entire tree, she says.
At the time, tumor microenvironment research focused on the circulatory and immune systems rather than on the nervous system, Venkatesh recalls. But as a PhD student in neuroscientist Michelle Monje’s lab, she discovered that neuronal activity promoted the growth and proliferation of aggressive brain tumors called high-grade gliomas, solidifying the connection between cancer and neuroscience. Earlier research in the lab had shown that glial precursor cells take their cues to grow and develop from neurons; because gliomas are thought to originate in glia and neural precursor cells, Venkatesh’s finding was, in her words, “groundbreaking,” but not far-fetched.
Erin Gibson, a neuroscientist at Stanford Medicine who was a postdoc in Monje’s lab when Venkatesh was there, says that the work stemmed from a fruitful partnership between two women: Monje, who bridged laboratory and clinical research, and Venkatesh, who conducted the interdisciplinary benchwork. “It really was a beautiful collaboration between the two of them,” Gibson tells The Scientist.
Venkatesh led a follow-up study that identified NLGN3, a protein involved in synaptic adhesion, as a driver of glioma growth. Knocking out the gene that encodes NLGN3 in mice blocked the growth of xenografts of human high-grade gliomas. A Phase 1 clinical trial is now underway to evaluate the safety of an NLGN3 inhibitor in children with high-grade gliomas—a full-circle moment that Venkatesh says she considers one of her proudest achievements.
“When my uncle got diagnosed . . . I want[ed] to do something that’s going to change how we treat cancer,” she tells The Scientist. “My work led to a clinical trial. That’s the translational impact that I really wanted to have, even as a kid.”
After completing a postdoc at Stanford in 2020 and teaching neurology courses for a year at the medical school, Venkatesh started her own lab at Brigham and Women’s Hospital and Harvard Medical School in Massachusetts. Her group extends neuroscience research beyond cancers originating in the brain, studying how peripheral neural circuits may influence cancer growth throughout the body, and whether these systems play a role when cancers metastasize to the brain.
Prospective group members are briefed on the lab’s own “microenvironment,” which Venkatesh describes as a diverse, inclusive, and comfortable space. “We’ve gotten a lot of [applications] from female graduate students who want to join the lab, and I think it has something to do with the fact that we have someone like Humsa at the helm,” says Kaylee Gentry, the lab’s manager. “She’s a person of color, she’s a woman, she is killing it—and she’s so friendly and down to earth at the very same time.” During the COVID-19 pandemic, Venkatesh collaborated on a commentary discussing how to support early-career scientists. “It happened to be young [principal investigators] who were hit hardest by COVID” personally and professionally, she says. “Now could be a time to change academia for the better.”