Biophysicist in Profile
Growing up as the fifth of six children in a small village near Hubei, China, Ye Fang never imagined becoming a scientist. Of his parents, who are both farmers, and his five siblings, Fang was the only one who had the opportunity to attend college, starting at Hubei University. “If not for biophysics, I am sure I would be a worker, like many of my villagers do nowadays in China,” said Fang.
During his final year of undergraduate study, Fang decided to pursue advanced education. “It was honestly not because I wanted to become a scientist,” he admitted, “but because graduate study had become increasingly popular in the late 1980s in China, and passing the required exams seemed very easy to me.” After completing his Bachelor of Science in chemistry, Fang completed his Master of Science degree in physical chemistry at Wuhan University. Fang then went on to become the first PhD student of Chunli Bai and Youqi Tang at the Institute of Chemistry at the Chinese Academy of Sciences (CAS). “It wasn’t until that point that studying science really became a reality for me,” said Fang. “I spent three years studying with Professor Bai, who is now the president of CAS, and Professor Tang, a renowned physical chemist.” His studies focused on the structure and biophysics of nucleic acid triple helix and scanning probe microscopy, including atomic force microscopy (AFM). In addition to serving as his PhD advisor, Bai influenced Fang’s careers in many ways. “He is the one who really led me into the scientific research field,” said Fang. Bai also taught Fang effective ways to build an open and positive working environment to maximize the potential of everyone in a lab, a skill which has surely benefited Fang’s career as an industrial researcher.
After completing his PhD in 1995, Fang pursued further training overseas. Jie Yang offered Fang the opportunity to continue his research in Yang’s newly established lab at the University of Vermont. “During my time in Vermont, I investigated the interfacial behaviors of bio-macromolecules onto and within lipid bilayers,” explained Fang. “Using AFM, we discovered that double stranded DNA molecules can spontaneously two-dimensionally condense onto supported cationic lipid membranes, and under such conditions, the DNA helix and pitches can be directly visualized.”
In 1996, Fang attended his first Biophysical Society Annual Meeting, held in Baltimore. While at the meeting, Lou-sing Kan, a friend of Fang and former professor at Johns Hopkins University (JHU), introduced Fang to JHU, and Fang became enthralled with its incredible research environment. Later that year, Fang seized the opportunity to join the lab of Jan Hoh in the Department of Physiology at the JHU School of Medicine. “At the time, DNA sizing was considered the centerpiece of human genome analysis,” said Fang, “and Hoh was interested in developing an AFM-based automated DNA sizing approach.” Fang worked on the project, which turned out to be quite a challenge, as the surface has a huge impact on how DNA behaves, and the mobile cationic molecules at the surface can direct DNA condensation.
This experience in DNA and biomembranes not only helped Fang specialize in this area, but helped him find his first senior research scientist position, with Corning Incorporated in 2000. “Working in an industrial research lab is an extremely exciting experience,” said Fang. “The problems that are significant to the customers and the market not only require fundamental understanding, but also demand practical solutions.” The invention of air-stable G protein-coupled receptor (GPCR) microarrays was a direct result of Fang’s research, thanks to his past experience in supported lipid membranes and surface chemistry. Though the company faced difficulty commercializing the invention, Fang did not give up. Instead, he focused his energies on developing a novel label-free biosensor-enabled whole cell phenotypic profiling technology known as dynamic mass redistribution (DMR) assays to aid in the drug discovery process. During his time as a consultant at Corning, Stephen Benkovic worked with Fang on the technology, saying, “In my opinion, Ye was the most influential scientist working for its creation and development.”
Since that idea was commercialized in 2006 as the Epic® system, Fang has been further motivated by customer feedback to understand the science behind the technology, as well as the biological implications of such a new measurement. “My continuous investigation following this feedback led to the discovery of the GPCR regulation of purine de novo biosynthesis, a novel GPCR mitogenic signaling pathway, as well as tyrosine metabolites as possible natural agonists for an orphan receptor, GPRCR35.” Even with the new technology, the linking of purinosomes assembly to G coupled receptors would not have been possible without Fang. “His choice of pharmacophores, his painstaking execution of the experiments, and his singular ability to meaningfully interpret complex patterns of data, were invaluable to the project,” said Benkovic.
Though he started in DNA and biomembranes, as his tenure at Corning has extended, so have Fang’s areas of research, now to include biosensors, systems biology, chemical biology, drug discovery, pharmacology and bioprocess. Today, Fang is the research director and a research fellow of the Department of Biochemical Technologies in the Science and Technology Division of Corning Incorporated. “As the director of the department, I am responsible for identifying and establishing new research projects that have great potential for the company,” he explained. “Currently, our research focuses on genomics, advanced cell culture technologies, biosensors, and bioprocess.”
Throughout his career, Fang has faced the challenge that many industrial researchers must face—how to balance personal interests with corporate interests and still fulfill management responsibilities. As he has advanced at Corning, the increasing responsibilities have forced Fang to find a way to marry his personal interests with corporate interests. His free thinking, as described by Terry Kenakin, who met Fang through the annual Corning-sponsored meeting for label free technology, has helped him maintain this balance. “Ye is not hampered by the biases and constraints of classically trained pharmacologists—such as me,” Kenakin said. “All scientists are trained under sets of rules, which keep order in our thinking, but can also be confining. When I work with Ye, there are no such constraints—it is refreshing, and gives me impetus to rethink ideas in a different way.”
Even working as a bioengineer, Fang considers biophysics a core competency for most of the research activities he has been working on for the past several years. “Understanding the physics behind any new biological measurement is essential to advance our technologies,” said Fang. “Watching our innovations turn into real products, and the joyful moments when we hear a great story from collaborators or customers wherein our product was essential to their discovery, is extremely rewarding.”
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