December 7, 2024

Bridging science and humanity

Daniel Chen’s journey into research began with a fascination for ancient cultures and extinct creatures. As a middle schooler, he was captivated by archaeology and paleontology, dreaming of working at excavation sites, unearthing ancient bones and tracing the histories of lost civilizations.

Over time, that early curiosity shifted toward biology, particularly as computational modeling emerged as a powerful tool. “I wondered if we could apply those methods to understand the past,” Chen explains. “I realized I could explore modern science by using data to uncover the mysteries of the natural world.”

In middle school, Chen channeled his curiosity by applying to the University of Washington’s Robinson Center, a renowned program for academically-motivated students to enter the UW early, sometimes bypassing traditional high school altogether. It was there that he led his first research project.

“I thrived by having the freedom to take initiative,” Chen explained. “The Robinson Center and the Office of Undergraduate Research supported me to push the boundaries of what I could explore.”

Chen’s first hands-on research experience came through a project studying invasive species in the Puget Sound area, under the guidance of Dr. Emily Jacobs Palmer. Focusing on nutria, a rodent that disrupts local ecosystems, the project introduced him to molecular biology and PCR techniques. “I learned how to think critically and independently,” Chen recalls. “That experience was the spark that set me on my path in research.”

A public promise

By his freshman year, Chen had solidified his commitment to biology and research. Early on, he faced the inevitable challenges of scientific inquiry. “I hit a point where I thought, ‘How do I handle negative results?’” he recalls. “A mentor taught me that hiding failures is never okay. Science is about honesty and persistence.”

This became a pivotal moment for Chen, as he reflected on how to stay true to his scientific curiosity. Fascinated by how Mycobacterium abscessus toxins damage immune cells in hospital-acquired infections, he focused on bacterial pathogenesis — a pursuit that shaped his work in personalized cancer immunotherapy.

In the summer of 2019, Chen joined the Institute for Systems Biology, where he studied how cancerous skin cells transform into drug-resistant, brain-like cells. The fast pace of computational research, offering immediate results, fueled his innovative, data-driven approach. When the coronavirus pandemic hit, Chen’s team shifted focus to studying the immune response. One finding that stood out was that preclinical autoimmune diseases, such as lupus, were significant factors for severe COVID-19. This hit close to home for Chen, as his paternal grandmother had passed away from lupus. The insight drove his research in autoimmune diseases, ultimately helping Chen earn the prestigious Marshall Scholarship in 2022, which enabled him to continue his work on autoimmune diseases and cancer immunotherapy at the University of Cambridge.

Tiny receptors + large-scale data = transformational treatments

At Cambridge, Chen’s current research focuses on receptors called GPCRs (G-Protein Coupled Receptors), which play a crucial role in controlling most signaling within the human body. Many of these receptors, including one called GPR85, remain shrouded in mystery.

GPR85 is particularly intriguing to Chen because it has the same exact sequence in both humans and great primates, yet scientists don’t know what it binds to or what its exact function is in the brain. To uncover its mysteries, Chen uses advanced computational models, like UW Professor and Nobel Prize-winner David Baker’s Rosetta method, to predict potential molecules it might interact with. Once a likely candidate is identified, he tests it in the lab to confirm whether the receptor binds and triggers the expected cellular responses. Early results are promising, suggesting that GPR85 does indeed interact with its predicted target.

Chen’s work doesn’t stop at identifying what the receptor binds to; he’s focused on understanding where and why it matters in the body. This is where his work with Professor Sarah Teichmann at Cambridge comes in. Together, they’re leveraging large-scale data from the Human Cell Atlas to explore how GPR85 might be influencing different tissues and systems. By mapping its effects, they aim to uncover how this receptor could contribute to diseases or conditions, and ultimately, how it could be targeted for new, more effective therapies.

Chen’s research tackles two critical areas with the potential to transform treatments for autoimmune diseases and deepen our understanding of the human body. One key focus is identifying orphan receptors, those whose binding partners (ligands) remain unknown. While the immediate impact of his current work may be limited, given the severe disabilities or lethality associated with mutations in these receptors, the methods Chen is developing could be groundbreaking. By identifying ligands for these receptors, his research could lead to new therapeutic strategies for diseases like cancer and autoimmune disorders.

A global collaboration, a human connection

Driven by his commitment to global health and service, Chen seeks to create a lasting impact through collaboration and a real-world understanding of the challenges he aims to address. “Science is about collaboration, not isolation,” he says, emphasizing the importance of learning from those who have lived through these challenges. “To make an impact, I need to see the problem from all angles — especially from the perspective of patients. True solutions come when you experience the issue firsthand.”

Chen’s research on orphan receptors and autoimmune diseases like lupus reflect his approach to advancing both scientific discovery and patient care. His goal is to uncover universal mechanisms across diseases to identify precise targets for more effective treatments. Rooted in the belief that balance in biological systems is key to understanding disease, his work has the potential to revolutionize the treatment of autoimmune disorders, where the immune system mistakenly attacks the body’s own tissues.

After completing his studies at Cambridge, Chen will continue his path at UCLA, where he will join the MD-Ph.D. program and work with Dr. Anthony Ribas in cancer immunotherapy.

For Chen, service is a shared endeavor, fueled by a collective purpose. “I’ve learned so much from those I’ve worked with, whether in my microbiology program or with my Marshall cohort. Ultimately, it’s about building communities rooted in collaboration and growth. As I see it, ‘Let’s build this tree together and reach the top of the canopy.’”