Lin Leng, PhD, senior research scientist in the Bucala lab, retired on June 30, 2023, after more than two decades at Yale.
Leng grew up in Shanghai, China, where he earned a bachelor-of-science degree from Fudan University. He first became interested in medical research around 50 years ago, during a hepatitis B outbreak in China, before there was a vaccine or medicine to treat the illness. He conducted research in microbiology and biochemistry with two former Columbia University professors in Shanghai before coming to the U.S., where he was a postdoctoral fellow at the University of California San Diego, Memorial Sloan Kettering Cancer Center, and Cornell University Medical College. He then worked on blood type conversion projects as a senior research fellow at the New York Blood Center. Leng was granted a U.S. patent for his invention involving cloning the enzyme endo-beta-galactosidase to transform blood type A to type O.
In 1998, Richard Bucala, MD, PhD, Waldemar Von Zedtwitz Professor of Medicine (Rheumatology) and professor of pathology, Yale School of Medicine, and of epidemiology (microbial diseases), Yale School of Public Health, who was at the Picower Institute at the time, hired Leng to clone the receptor for macrophage migration inhibitory factor (MIF).
The MIF was cloned in the early 1990s, Bucala explains, but there was no information about the receptor. “I had assigned the cloning of the receptor to four successive postdoctoral fellows, and none had succeeded,” he said.
Bucala will never forget the day—several months later—when Lin came to him with a list of the DNA sequences of the isolated clones. “There were about 40 of them, and they were all different lengths of Class II-associated invariant chain, which, to my knowledge at the time, was not even known to be expressed on the cell surface,” Bucala said. The discovery opened new avenues of research, with an anti-MIF receptor antibody ultimately becoming an anticancer drug.
When Bucala moved his lab to Yale in 2002, Leng came with him.
Leng went on to characterize a second MIF signaling co-receptor, and he was instrumental in developing facile biochip assays for genotyping MIF, including methods that were applied in the lab’s epidemiologic studies in rural Africa, which established the evolutionary role of MIF in protection from lethal malaria, according to Bucala. “The same methods were used during COVID-19 to show that individuals with a high expression of the MIF gene were at greater risk for severe disease,” he said.
Over the course of his career, Leng has trained more than 20 scientists and co-authored nearly 230 publications. He is a vital international resource for technical knowledge about multiple recombinant proteins, monoclonal antibodies—which he was the first to develop—as well as important research methodologies, Bucala noted.
Fondly called Leng Laoshi—Teacher Leng—by Mandarin-speaking members of the Yale community, he is both a gifted scientist and a patient teacher, says Betty Hsiao, MD, assistant professor of medicine (rheumatology, allergy and immunology). “I first worked with him when I started as a research intern in the Bucala lab,” she said. “I had zero research experience, and he was incredibly patient and supportive, from teaching me how to pipette to helping me solve scientific issues with the project we were working on.”
An “awesome collaborator,” Leng could be counted on to find specialized reagents and experimental protocols that no one in the Bucala lab had used in 15 years, recalls Elias Lolis, PhD, professor of pharmacology. “I am going to miss the great but humble gentleman and scientist he was, whether at Yale or an MIF meeting halfway across the world,” Lolis said.
Leng is an unsung hero of MIF biology, says Maor Sauler, MD, associate professor of medicine (pulmonary, critical care and sleep medicine). “He has not only led key scientific efforts regarding the role of MIF in disease, but he also has an incredible fund of knowledge related to experimental biology in general,” Sauler said. “His contributions to the field are immense, and on a personal level, he will be greatly missed.”
Reflecting on his career, Leng is grateful for his experience at Yale School of Medicine. “I would like to thank the Department of Internal Medicine for giving us an excellent platform for research, collaboration, and innovation,” he said. “I don’t think we could have done what we did anywhere else.”
In retirement, Leng plans to attend seminars, visit museums, read, travel, spend more time with family, and continue helping out in the Bucala lab. “Just the other day, I received an inquiry from a university in Canada, and a graduate student said to me, ‘I have more questions,’” Leng said. “It’s okay. I will be here to answer.”