Professor Taekjip Ha is a world-renowned biophysicist whose pioneering work in single-molecule fluorescence and force spectroscopy has transformed how scientists visualize and understand molecular mechanisms. He is the George D. Yancopoulos in Honor of Frederick W. Alt Professor of Pediatrics at Harvard Medical School and a Senior Investigator in the Program in Cellular and Molecular Medicine at Boston Children’s Hospital, where he also serves as Director. A Howard Hughes Medical Institute Investigator since 2005, Prof. Ha is a member of the National Academy of Sciences, the National Academy of Medicine, and the American Academy of Arts and Sciences. His career has been marked by both technological innovation and biological discovery, earning him numerous accolades—including the Kazuhito Kinosita Award and the Gregory Weber Award—and establishing him as one of the leading figures in modern biophysics.
From Semiconductors to Single Molecules: A Career Defined by Curiosity
When asked what first drew him into the then‑nascent field of single‑molecule research, Prof. Ha reflects on a trajectory shaped as much by unexpected turns as by intentional choices. Early in graduate school, his research centered on semiconductor physics. About a year into the project, his advisors proposed building a new instrument—something akin to what we would now call super‑resolution spectroscopy—to study semiconductors.
"Soon after I finished building it, we realized that it was not ideal for semiconductors," Prof. Ha recalls. "But a high-profile paper had just shown that similar instruments could detect single fluorescent molecules." That realization shifted everything. The resulting pivot led him naturally to single‑molecule FRET, a direction he pursued because he wanted to push beyond what was already known about single fluorescent molecules and measure how two such molecules interact. "Eventually, FRET became a powerful way to study single biomolecules," he says.
Prof. Ha admits he had "zero interest in biology" at the time. DNA was simply a physical polymer he used for physics experiments. But the technology he was building turned out to be perfectly suited for answering biological questions that had been inaccessible. As the instruments improved, it became clear he was among the few—sometimes the only person—working in that direction. The ability to visualize molecular dynamics in real time made the field irresistible. "It confirmed that my contributions could be truly unique," he says. "That made me want to build my career around these experiments."
Mentors Who Shaped a Scientific Vision
Two mentors stand out prominently for Prof. Ha. His postdoctoral advisor, Steven Chu, inspired him to always ask why people should care about what one works on." Prof. Ha also credits Shimon Weiss, with whom he spoke almost daily during his PhD, for influencing how he framed research questions and evaluated the broader significance of new ideas.
Choosing Research Questions That Matter
For Prof. Ha, a worthwhile scientific question demands significant effort but also offers the possibility of a distinctive contribution. "You want to ensure your contribution is unique," he says. That uniqueness can come from inventing a new technology or from being among the best people equipped to use existing tools to tackle bold, unresolved questions. The ideal project, he emphasizes, combines technological ingenuity with deeper biological insight—a synergy that has defined much of his career.
The Next Frontier in Single‑Molecule Biophysics
Looking ahead, Prof. Ha sees enormous potential in applying single‑molecule approaches directly to patient‑derived tissues and clinical samples. "This would give us a unique opportunity to address biomedical problems from a different point of view," he says. Bridging laboratory precision with real‑world patient variability, he believes, will open new doors in disease diagnosis and mechanistic understanding.
Bringing Single-Molecule Approaches Into Cellular Contexts
Prof. Ha says, “It is now pretty straightforward to combine structural biology and single molecule measurements in a single project as they both require biochemically pure preparations and they provide complementary information, atomic resolution but static structures vs high temporal resolution without the ability to map the positions of all residues.” “The real hurdle”, he emphasizes, “is performing single-molecule measurements into the cellular environment, in particular measuring conformational dynamics, but improvements in protein modification and labeling technologies appear very promising.”
Training the Next Generation of Scientists
Prof. Ha has mentored many researchers who now lead their own laboratories, and he is deliberate about cultivating both creativity and independence. "Creativity grows when trainees are exposed to ideas beyond their immediate project," he explains. He encourages students and postdocs to read widely, attend diverse seminars, and participate actively in journal clubs. He also removes practical barriers by covering "the coffee and donuts that make journal clubs more inviting," ensuring conference travel opportunities each year, and arranging lunches with visiting speakers. These interactions, he says, spark unexpected connections and help trainees gain the confidence to explore their own scientific paths.
When asked what makes a good mentor, Prof. Ha is characteristically self‑reflective. "I learned from my own failures as a mentor," he says, noting that these experiences led him to read about managing people and building healthy lab dynamics.
The Role of Scientists in Public Communication
For Prof. Ha, effective science communication requires connecting rigorous scientific work with the fundamental desire to help humanity. "If you can connect your desire to help humankind with meaningful scientific contributions, the message resonates," he says.
A Hypothetical New Direction: The Biology of Infertility
If he could begin an entirely new project tomorrow, Prof. Ha says he would study infertility. He suspects that issues in DNA mechanics during meiosis may underlie certain forms of infertility—a hypothesis he finds compelling, though he admits he does not yet have a practical research plan for pursuing it.
If Not a Scientist…
"I would have been a farmer," he says with a laugh. Gardening—particularly growing vegetables—has unexpectedly taught him some biology along the way.
Current Research in a Nutshell
Prof. Ha summarizes his current research focus succinctly for a general scientific audience:
"We study genome maintenance at the highest possible resolution—how DNA is duplicated and repaired accurately to prevent disease. Our tools allow us to visualize these processes in space and time, always aiming for higher resolution than yesterday."
Lab page: www.tjhalab.com
Twitter: @taekjip