A Journey Driven by Curiosity

As a pharmaceutical science student at Pokhara University in Nepal, Professor Rajendra Karki was fascinated by fundamental questions: How do drugs work at the molecular and cellular levels? Why are different drugs prescribed for the same disease? These questions sparked his curiosity about how drugs can be used therapeutically and ultimately led him to Korea.
“To pursue pharmacology research more seriously, I enrolled in graduate school at Mokpo National University. While studying herbal medicine resources, I was introduced to experimental biomedical research. Assisting my advisor with angioplasty procedures gave me firsthand exposure to pharmacological interventions.”
After completing his master’s and doctoral studies, Karki applied for postdoctoral positions in the United States, but the path was far from easy. His background in herbal medicine, a relatively unfamiliar field in the United States, worked against him. After several rounds of applications, he secured a position at the University of Missouri–Kansas City (UMKC), where he continued studying innate immunity and inflammatory signaling. He later joined St. Jude Children’s Research Hospital, one of the world’s leading research institutions for serious pediatric diseases.
“At first, I was overwhelmed by the lab's size and competitive atmosphere. Fortunately, its strong commitment to translational research and therapeutic focus turned my background in pharmacology into a unique strength.”
It was then that the steps of his journey—from Nepal to Korea and ultimately to the United States—began to converge, marking a turning point in his research career. A question that would challenge conventional wisdom had begun to take shape.

Looking Beyond the Obvious

The question that intrigued Karki concerned cell death¹, or how cells die. Cell death normally serves a protective role by containing infections caused by pathogens² and preventing tissue damage from spreading. But when it becomes excessive, inflammatory molecules released by dying cells can also damage healthy tissue. That's why keeping cell death under control is so important. At the time, researchers assumed that each cell death pathway acted on its own. If one pathway could be blocked, they believed, cell death could be prevented. However, his subsequent research began to reveal the limitations of this view.
“Pathogens carry a variety of molecules that can stimulate cells. I wondered if infected cells might be receiving signals from several of those molecules at the same time, so I tested the effects of blocking multiple cell death pathways concurrently. I first blocked one pathway, then two together, but nothing changed. When I blocked three or four pathways, however, the cells stopped dying. We coined the term PANoptosis³ to capture the idea that the three cell death pathways function as a single, integrated program, but the scientific community wasn't ready to accept the idea.”
PANoptosis marked a significant shift in the understanding of cell death, raising many questions that Karki addressed one by one in subsequent papers. As it happened, the discovery coincided with the COVID-19 pandemic, when interest in cytokine storms⁴—where an overactivated immune response attacks the body's own tissues—surged. Karki linked PANoptosis to the mechanisms underlying severe COVID-19, and his findings, published in Cell in 2021, drew worldwide scientific attention.

¹ Cell death: A natural process by which cells undergo programmed death to remove damaged or infected cells and protect the body. It can be classified into several distinct pathways depending on how it occurs.
² Pathogens: Microorganisms, such as viruses, bacteria, and fungi, that invade the body and cause disease.
³ PANoptosis: A process in which three cell death pathways once thought to function independently are integrated into a single, coordinated program. The prefix “pan” comes from Greek and means “all.”
⁴ Cytokine storm: A condition in which excessive amounts of chemical messengers used for communication between immune cells are released, triggering uncontrolled inflammation that damages healthy tissues.

Process Over Outcome, Together Over Alone

Karki joined the faculty of the School of Biological Sciences at Seoul National University (SNU) in 2023 and was named Clarivate Highly Cited Researcher (HCR) in both 2024 and 2025. Members of the Lab of Innate Immunity and Cell Death, which he leads, say, “Professor Karki is the pride of our lab.” However, he sees things differently.
“The recognition I’ve received isn’t mine alone. It belongs to everyone. I owe it to the ideas, dedication, and hard work of my students, researchers, and collaborators. If anything, I consider myself fortunate to have had the opportunity to work in such a supportive environment.”
This good fortune is also the result of his thoughtful and caring approach to mentoring. Professor Karki is rigorous when it comes to the fundamentals of research, while also creating an environment where everyone feels comfortable sharing ideas. One principle stands above the rest: Always document unexpected results. “Even negative results can serve as valuable controls. In science, failure is information.”
Today, Professor Karki is embarking on his next research endeavor to uncover how cellular metabolism shapes innate immunity and regulates inflammatory responses. As this research advances, it could pave the way for new therapeutic strategies to treat infectious and inflammatory diseases, as well as metabolic disorders such as obesity and diabetes, without directly targeting pathogens. Rather than offering a timeline, Professor Karki responded with his research philosophy.
“I tell my students all the time that if your only goal is good grades or a degree, you won't last very long. After all, experiments often fail, and progress can be painfully slow. But if you hold on to your curiosity and passion while maintaining a healthy work–life balance, you'll naturally find your way to where you want to be.”

The Metabolic Circuitry of Cell Death,
illustrating how metabolites regulate inflammatory cell death