Fifth-year Yale School of Medicine (YSM) MD-PhD student Ryan Dz-Wei Chow is one of 30 graduate students selected for the Paul & Daisy Soros Fellowships for New Americans. This year’s pool of 2,445 applicants was the largest ever. The fellows are immigrants and US-born children of immigrants who are poised to make significant contributions to US society, culture, or their academic field. Chow, whose parents immigrated to the United States from Taiwan before he was born, grew up in Silicon Valley in an environment he said “celebrated innovation and exploration of the unknown.”
Chow’s PhD thesis focuses on engineering the immune system to eliminate cancers. Over the past decade, it has been shown that immunotherapies, which aim to unleash the body’s own immune system against tumors, can have impressive responses, but only a small fraction of patients will respond to treatment. Chow has been developing new strategies to improve the efficacy of immunotherapy.
He “loves how oncology is a field that fosters a culture of creativity and discovery, along with the humility to draw inspiration from other fields.” Moreover, since nearly 40% of Americans will be diagnosed with cancer, Chow is inspired to be doing work that can have a direct impact on such a large patient population.
Chow works in the lab of Associate Professor Sidi Chen, PhD, who describes him as “an outstanding student, excellent scientist, and awesome human being. He’s absolutely the future star!”
Chow first remembers being interested in science when his fifth-grade teacher spent an entire class discussing “where do babies come from?” While he found the topic “extremely uncomfortable,” he also recalls thinking “it was really cool that all of us had come from a single fertilized egg!”
His interest in science developed further in his early to mid-teens—and expanded to regenerative medicine—when as a nationally-ranked junior tennis player he experienced numerous injuries that made it difficult for him to compete. He spent a high school summer in the lab of Irving Weissman at Stanford University and was fascinated by the orchestrated processes that underlie tissue repair, and how the dysregulation of these normal regenerative mechanisms can lead to cancer.
During college at Harvard, Chow joined the lab of Jayaraj Rajagopal, a pulmonologist at Massachusetts General Hospital, and investigated the mechanisms by which lung cancers can shapeshift into different subtypes and become resistant to therapies. From pursuing this line of study, Chow was inspired to become a physician-scientist and tackle challenging problems that could impact patient care.
Chow was drawn to YSM’s MD-PhD Program because of its track record of mentoring physician-scientists and Yale’s outstanding cancer immunology research. During the revisit weekend for admitted students, Chow met with Chen’s lab and learned about the exciting genome editing technologies they were developing. He worked in Chen’s lab the summer before starting medical school through YSM’s START Program, and joined the lab soon after.
Chow already has made many scientific contributions to the field of cancer immunology, including discovering mutations that increase the effectiveness of immunotherapy. This work may prove valuable for predicting the efficacy of immunotherapies in specific patients and for gaining a window into potential new therapeutic strategies. For example, Chow explains, “by deliberately manipulating the genetic pathways that we identified, it may be possible to pharmacologically sensitize tumors to immunotherapy.”
He also co-invented a therapeutic modality that overrides the camouflage that tumors use to evade the immune system. This therapy causes tumors to reveal themselves to the immune system, which hinders them from developing and growing. Chow explains that he and his lab colleagues “reasoned that we could repurpose CRISPR genome editing technologies to force tumors to ‘showcase’ their mutant proteins, like holding up a big spotlight for the immune system to zero in on.”
Chow also has identified genes in T cells— a type of immune cell that is essential for anti-tumor immunity— that restrain their ability to destroy tumors. “By targeting these genes, we can engineer T cells that are better able to fight against cancers.”
The most challenging aspect of Chow’s research is identifying questions that can simultaneously advance our understanding of fundamental biological principles and have the potential to impact clinical care, all while being technologically and financially feasible. “In order to push through the inevitable setbacks and failures of scientific research, I think it's essential that you can clearly articulate to yourself and others why the project you're working on is worth persevering for,” Chow states.
For Chow, the most rewarding part of research is when he proves himself wrong by getting an unanticipated result. “One thing that my undergraduate mentor, Jay Rajagopal, told me is that real science happens when things don't go the way you expect. It's such a beautiful way to look at science, and that's really stuck with me ever since.”
Chow, who joins 16 other Soros Fellows for New Americans who currently attend or are graduates of YSM, is “deeply honored to be joining this incredible community of New Americans and excited to continue exploring the world of cancer immunology.”