Beyond Synthesis: Professor Zhang Yan of Tianjin University School of Pharmaceutical Science Pioneers Drug Development and In Vitro Diagnostics via Proprietary Synthetic Biology Platforms
The 21st Century Is the Century of Biology.
In the 1990s, the popular notion that “the 21st century would be the century of biology” sparked a surge in students pursuing biotechnology studies in China. Biology-related majors became the most competitive programs at many universities, requiring the highest entrance exam scores for admission. In 1992, Zhang Yan, having just completed the National College Entrance Examination, also applied to major in biochemistry. However, by the time he graduated with his bachelor’s degree in 1996, China’s biotechnology industry was still developing slowly.
“In 1996, fresh graduates had to go through three rounds of interviews to join foreign companies, with a monthly salary of RMB 2,400. However, pursuing a Ph.D. in biology in the United States on a full scholarship meant not only tuition-free education but also a monthly stipend of over USD 1,000. At the exchange rate of 1:8 at that time, this amounted to more than RMB 10,000—six to seven times the compensation offered by foreign firms. Due to the underdevelopment of China’s domestic biotechnology industry and the attractiveness of the U.S. scholarship system, a large number of biology undergraduates from prestigious universities chose to study for doctoral degrees in the United States from the late 1990s to the early 2000s. Having achieved academic success and accumulated extensive experience in scientific research and industrialization in the U.S., these individuals have become the main force among returnee professionals in the biotech sector over the past decade,” he recalled.
“At that time, China’s economy was relatively underdeveloped; without a full scholarship, I might not even have been able to obtain a visa,” Zhang Yan told Chengguo Bureau. During his doctoral studies at the University of Pennsylvania, he dedicated himself to using yeast as a model organism and employing genetic approaches to investigate the relationship between iron metabolism defects and various human hematologic and neurodegenerative diseases.
After completing his Ph.D., Zhang Yan was retained by his doctoral advisor to conduct postdoctoral research in the laboratory for two years, owing to his outstanding performance during his doctoral studies. In 2008, JoAnne Stubbe’s laboratory in the Department of Chemistry at the Massachusetts Institute of Technology (MIT) recruited a postdoctoral fellow to address a long-standing research challenge: elucidating the biosynthetic mechanism of the cofactor for ribonucleotide reductase, a cancer drug target under extensive investigation in her lab. This iron-containing enzyme prompted urgent questions within the research team regarding how it acquires iron and, subsequently, how it obtains electrons to assemble its complex cofactor—questions that required the application of genetic techniques. Zhang Yan’s expertise in genetics made him an ideal candidate for this role. Upon joining the group, he quickly adapted to the high-pressure environment of Stubbe’s laboratory and acquired interdisciplinary knowledge and research skills in enzymology, protein chemistry, and bioinorganic chemistry. “The standards in this laboratory were exceptionally high; most postdocs dropped out midway, which deterred many Ph.D. students in the field from applying. As I came from a different disciplinary background, I was initially unaware of this situation. You could say my ignorance gave me courage, but I ultimately survived, becoming the only postdoc with a biological science background in Stubbe’s laboratory to remain in academia,” he joked. During this period, working overnight became routine. Ultimately, by integrating biological and chemical approaches, he resolved key scientific questions and published several significant papers. JoAnne Stubbe later introduced Zhang Yan as the collaborator who had co-authored the most publications with her among the more than 100 postdoctoral fellows in her group’s history. To this day, Zhang Yan maintains the habit of sleeping only about five hours per day.
For Zhang Yan, the postdoctoral experience at the Stubbe Lab at MIT, which boasts a distinguished track record, was of paramount importance.
In addition to weekly updates on individual research project progress, the laboratory holds a Journal Club each week. During these sessions, 3–4 participants each give a 5-minute presentation to introduce notable papers they have reviewed that week. Additionally, one person delivers a 45-minute in-depth report, providing a comprehensive and detailed analysis of a selected paper’s background, research content, and technical extensions.
In this way, young scientists can stay abreast of the most cutting-edge technological developments in real time. “MIT students are highly intelligent and possess an extraordinary scientific intuition early in their research careers. Many currently prevalent technologies, such as CRISPR and CAR-T, as well as emerging hotspots like ferroptosis, were identified by our research group at their nascent stages and subsequently discussed and studied in our Journal Club.”
On the other hand, since the laboratory belongs to the Department of Chemistry at MIT, Zhang Yan’s experience there involved interdisciplinary research. This interdisciplinary background continues to play a significant role in his current work.
“My lab’s current efforts to discover new enzymes and novel metabolic pathways from the natural microbial world are largely influenced by that earlier research.” Using chemical intuition to guide biological research and uncover previously unknown enzymes is what Zhang Yan calls “chemically guided bioinformatics.”
MIT’s technology transfer achievements are world-renowned, but Zhang Yan’s efforts in translating scientific and technological innovations into practical applications began only after he returned to China.
“Time flies. It has been more than ten years since I went from the University of Pennsylvania to MIT, and then joined R&D Systems Inc., a pioneer in recombinant protein technology,” he continued. He noted that the landscape for biological innovation in China had undergone earth-shaking changes, while his parents were gradually aging—he felt it was time.
In 2014, Zhang Yan left Andy Company and returned to China, where he established his own laboratory at Tianjin University. Employing approaches such as bioinformatics, genetics, biochemistry, and biophysics, he discovered and characterized novel enzymes and metabolic pathways in nature, yielding notable scientific achievements including “blue roses” and “skatole.” In 2021, he led his team to elucidate the biosynthetic mechanism of Z-base DNA, with their findings published in Science.
Meanwhile, the team is applying this achievement to the detection of single-base mutation diseases. “Some single-point DNA mutations can also lead to diseases, such as cancer,” explained Zhang Yan. “Detecting single-base mutations amidst a 1,000-fold ‘high-background’ noise in peripheral blood holds broad application prospects in postoperative tumor monitoring, precision medication guidance, eugenics and healthy reproduction, and infectious disease testing.”
"Some of our current research and applications in the biopharmaceutical field have already entered the animal testing phase," revealed Zhang Yan.
Zhang Yan established his own startup, “Zhongke Meining.” Leveraging a foundational synthetic biology development platform, the company has achieved breakthroughs across three dimensions—nucleic acids, proteins, and chassis organisms—to produce high-value-added products for application in the broad fields of in vitro diagnostics and microbial therapeutics.
Zhang Yan believes that translational research requires sustained investment and that a balance between R&D spending and commercialization should be considered. To this end, he has divided the company’s R&D pipeline into three segments: short-term, medium-term, and long-term. At the forefront are translational applications in immunodiagnostics, while nucleic acid rapid testing, represented by single-base mutation detection, occupies the middle tier. The R&D cycle in the in vitro diagnostics (IVD) field is relatively short; some products have already entered the regulatory submission phase, enabling faster cash flow generation. In contrast, drugs based on microbial therapy for metabolic diseases fall under the long-term R&D pipeline.
“If all goes well, we should have products ready for market entry soon. In the early stages, we primarily relied on our own funds and have already completed the construction of our GMP-compliant manufacturing facility,” he stated. Of course, the company has already attracted close attention from a number of investment firms.
“Although our current team is small, it is fully functional. Moving forward, we aim to further diversify our product pipeline, bring our products to market sequentially, and scale up our operations. Simultaneously, by securing investment, we hope to attract more industry talent to support the company’s commercialization efforts and achieve rapid growth,” said Zhang Yan when asked about the next steps.
Chair Professor and Doctoral Supervisor at the School of Pharmaceutical Science and Technology, Tianjin University. He received his Ph.D. in Genetics from the University of Pennsylvania in 2006 and subsequently conducted postdoctoral research in the Department of Chemistry at the Massachusetts Institute of Technology. In 2015, he was selected for the Tianjin Young Thousand Talents Program and recognized as a Leading Talent in Scientific and Technological Innovation among Young and Middle-aged Researchers in Tianjin. In 2021, he was awarded the National Science Fund for Distinguished Young Scholars.
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