Jianmin Cui didn’t set out to study ion channels. He started college as a physics major with a growing curiosity about biology, drawn in by books that bridged the two fields. “The physical mechanisms of the various biological phenomena were fascinating to me,” Cui says. After earning his undergraduate degree, he was accepted into a master’s program in biology, where he began recording and analyzing electrical signals in the nervous system of silkworms as they responded to pheromones—his first real taste of biophysics research.
His curiosity about the natural world started when he was a child. Cui grew up in Nanjing, China, on the campus of Nanjing Forestry University. “I was exposed to a variety of specimens of plants, insects, and animals in my childhood,” he explains, a circumstance he credits with sparking his interest in biology. His parents, both civil engineers, reinforced that interest. His father built water towers, reservoirs, and buildings in rural areas, and Cui often tagged along. “Traveling with him during his work in my childhood also exposed me to the nature of plants and animals,” he remembers.
Cui earned his bachelor’s degree in physics and a master’s in biophysics from Peking University in Beijing, before moving to the United States to complete a PhD in physiology and biophysics at Stony Brook University.
Looking back, Cui says the timing of his PhD training shaped the direction of his entire career. He explains, “When I joined Dr. Ira Cohen’s lab for my PhD studies, the genes encoding various ion channels were rapidly being identified. New ion channel clones were published nearly every week. The availability of genetic information and molecular clones enabled various new methods to be adopted in ion channel studies. Novel findings and more profound mechanistic questions emerged in journals and conferences constantly.” He describes Cohen’s lab, and the wider community around it, as an especially energizing place to be. “It was an exciting time for ion channel research,” he notes. Cohen encouraged him to study cardiac ion channels at the molecular level and connected him with other labs to learn new techniques—making mRNA and expressing channels in Xenopus oocytes, molecular cloning, and biochemistry techniques. “I found joy in the exquisite work of ion channel molecules,” Cui says.
He started his postdoctoral training under Cohen and Gail Mandel at Stony Brook University, where he worked on cloning a brain inward rectifier ion channel—a project that wrapped up once another lab published the first cloned channel of that type. Needing a new postdoctoral position, Cui then joined Richard Aldrich’s lab at Stanford University to study BK-type calcium-activated potassium channels, just after the gene encoding the channel had been identified. Working alongside another postdoc, Cui helped show that voltage and calcium can each activate BK channels independently, but that both also work together to promote channel opening—work that led to a new allosteric model for how the channel is activated.
Today, Cui is a professor in the Department of Biomedical Engineering at Washington University in St. Louis, where his lab pursues several lines of research. One focuses on KCNQ1 and the cardiac IKs channel it forms with the regulatory subunit KCNE1—a channel important for terminating cardiac action potentials and regulating heart rate. His group studies how voltage, the membrane lipid PIP2, calmodulin, and KCNE1 work together to activate the channel, work that has fed into a collaborative effort to discover compounds that could reduce dangerous prolongation of cardiac action potentials.
A second line of research returns to BK channels, this time examining how mutations linked to neurological disorders—including epilepsy, movement disorders, autism, and cerebellar atrophy—alter channel function. Because some of these mutations increase channel activity and others decrease it, the connection between a given mutation and a patient’s symptoms isn’t always obvious. Cui’s lab has found that several mutations linked to different symptoms can converge on the same underlying mechanism of channel activation, connected through shared allosteric pathways within the channel’s structure—a finding he hopes will inform the design of more targeted treatments.
A third project explores sonogenetics: using ultrasound to activate mechanosensitive and thermosensitive ion channels introduced into tissue through genetic methods. Because ultrasound can reach deep into tissue non-invasively, Cui sees potential clinical applications for treating neurological disorders and diabetes, and his lab is working to develop more effective, ultrasound-specific channel actuators for the approach.
Asked about the biggest challenge of his career, Cui points not to a single event but to a recurring one: the start of any new project, when the central questions still need to be defined. “Such questions may emerge after pilot experiments and solid biophysical analyses,” he notes.
What keeps him engaged is the analytical process itself. “I enjoy the process of identifying fundamental questions, designing experiments, and understanding mechanisms of ion channel function by analyzing experimental results,” Cui shares. “The moment when a mechanistic understanding emerges from the data and analyses is exhilarating.” He’s equally energized by the people behind the science. Cui says he’s learned as much from his students and postdocs as they have from him, and he considers those exchanges the most rewarding part of the job. “My career is built on the scientific achievements of the trainees,” he declares, “and it is satisfying when their success in science started from our work.”
Cui has watched the field transform twice over the course of his career—first through the wave of ion channel gene discoveries beginning in the late 1980s, and now through advances in atomistic structural biology and computational methods. He expects these tools to keep deepening scientists’ understanding of how channels sense stimuli, bind ligands, and open their pores, as well as how they interact with other proteins in the cell. “Our current research is trying to align with and hopefully add to these exciting advances,” he says.
The Biophysical Society has been part of Cui’s career since he was a graduate student. He attended his first BPS Annual Meeting in 1988 and has missed only one or two since. “In these meetings I have met and become familiar with fellow biophysicists, learned their science and opinions on current topics, and received valuable feedback on our own work,” he reveals. He now encourages the same habit in his own trainees, pushing them to present their work, ask questions, and explore sessions outside their immediate research area to broaden their scientific horizon.
Outside the lab, Cui spends his time with family, cooking, exercising, reading, and traveling. When asked what career he might have pursued instead of biophysics, he doesn’t have a ready answer: “My experience in biophysical research makes biophysics not only my career but also my passion.”