Aashish Manglik thinks of himself as an unconventional thinker. It’s an identity shaped by growing up as an Indian immigrant in the Midwestern United States, where he often felt he would never quite fit in as an “American,” even after becoming a naturalized citizen.

“I think this instilled in me a desire to be the person who ‘thought differently’ in any group,” Manglik reflects. “This nonconformist thinking has helped me pick areas of science that are unique from what others are working on, or choose approaches that others may not take on.”

That outsider perspective has served him well over the years. As a physician-scientist at the University of California, San Francisco, Manglik’s work has reshaped how scientists understand cellular communication, uncovering hidden complexity in the molecular switches that control everything from the heartbeat to pain perception. Specifically, Manglik’s research focuses on how cells sense and respond to the world. 

“Just like we use our eyes and nose to see and smell, the cells inside us have their own ways of detecting what’s happening, like knowing when adrenaline is pumping during a stressful moment, or when blood sugar rises after a meal,” he explains. “These signals are how cells ‘talk’ to each other.”

Revealing Nuances

The key players in this interaction are G protein–coupled receptors (GPCRs), which are molecular sensors embedded in cell membranes. For decades, scientists viewed these receptors as simple on-off switches. But Manglik’s work revealed something far more nuanced.

These GPCRs exist in a rich landscape of conformations linked to distinct outcomes. Rather than binary switches, these receptors are sophisticated instruments that produce different signals depending on their precise molecular shape.

“This recognition of conformational flexibility not only explains the complexity of GPCR signaling but also opens the door to a new generation of medicines designed for exact cellular communication,” Manglik says. 

The implications of these results span medical fields. Unlocking the conformational complexity of GPCRs allows researchers to create molecules that produce specific therapeutic effects, while potentially avoiding unwanted side effects.

“I enjoy learning about completely new areas of biology and medicine, the technological advances in diverse fields, and how to combine these with the research that we do in my lab,” Manglik says. “This creative playfulness to science keeps me motivated.”

Manglik has translated his discoveries into practical applications, founding two biotechnology companies: Stipple Bio and Epiodyne, which develop new therapeutics based on Manglik’s findings.

Immigrants Cross Borders in Life and Science 

The recognition that comes with the Vilcek Prize for Creative Promise holds particular meaning for him as an immigrant. “It affirms the choice to leave one home in search of possibility in another,” he says. “To be recognized alongside such extraordinary past recipients is an honor, and the real credit goes to my amazing trainees whose talent makes our discoveries possible and science worth doing.”

His career demonstrates that different viewpoints are invaluable. By refusing to accept conventional wisdom, Manglik has uncovered fundamental principles of how our cells react to the world, paving the way for new methods to treat disease.

His advice to young immigrant scientists reflects this perspective: “As immigrants, you’ve already crossed borders others wouldn’t. Do the same in science. Don’t settle for the mapped continents of knowledge; strike out for the undiscovered ones.”