Jane-Jane Chen: A model scientist who inspires the next generation

Growing up in Taiwan, Jane-Jane Chen excelled at math and science, which, at that time, were promoted heavily by the government, and were taught at a high level. Learning rudimentary English as well, the budding scientist knew she wanted to come to the United States to continue her studies, after she earned a bachelor of science in agricultural chemistry from the National Taiwan University in Taipei.

But the journey to becoming a respected scientist, with many years of notable National Institutes of Health (NIH) and National Science Foundation-funded research findings, would require Chen to be uncommonly determined, to move far from her childhood home, to overcome cultural obstacles — and to have the energy to be a trailblazer — in a field where barriers to being a woman in science were significantly higher than they are today.

Today, Chen is looking back on her journey, and on her long career as a principal research scientist at the MIT Institute for Medical Engineering and Science (IMES), a position from which she recently retired after 45 dedicated years.

At MIT, Chen established herself as an internationally recognized authority in the field of blood cell development — specifically red blood cells, says Lee Gehrke, the Hermann L.F. Helmholtz Professor and core faculty in IMES, professor of microbiology and immunobiology and health science and technology at Harvard Medical School, and one of the scientists Chen worked with most closely. 

“Red cells are essential because they carry oxygen to our cells and tissues, requiring iron in the form of a co-factor called heme,” Gehrke says. “Both insufficient heme availability and excess heme are detrimental to red cell development, and Dr. Chen explored the molecular mechanisms allowing cells to adapt to variable heme levels to maintain blood cell production.”

During her MIT career, Chen produced potent biochemistry research, working with heme-regulated eIF2 alpha kinase (which was discovered as the heme-regulated inhibitor of translation, HRI) and regulation of gene expression at translation relating to anemia, including:

• cloning of the HRI cDNA, enabling groundbreaking new discoveries of HRI in the erythroid system and, notably, most recently in the brain neuronal system upon mitochondrial stress and in cancers;
• elucidating the biochemistry of heme-regulation of HRI;
• generating universal HRI knockout mice as a valuable research tool to study HRI’s functions in vivo in the setting of the whole animal; and
• establishing HRI as a master translation regulator for erythropoiesis under stress and diseases.

“Dr. Chen’s signature discovery is the molecular cloning of the cDNA of the heme regulated inhibitor protein (HRI), a master regulatory protein in gene expression under stress and disease conditions,” Gehrke says, adding that Chen “subsequently devoted her career to defining a molecular and biochemical understanding of this key protein kinase” and that she “has also contributed several invited review articles on the subject of red cell development, and her papers are seminal contributions to her field.”

Forging her path

Shortly after graduating college, in 1973, Chen received a scholarship to come to California to study for her PhD in biochemistry at the School of Medicine of the University of Southern California. In Taiwan, Chen recalls, the demographic balance between male and female students was even, about 50 percent for each. Once she was in medical school in the United States, she found there were fewer female students, closer to 30 percent at that time, she recalls.

But she says she was fortunate to have important female mentors while at USC, including her PhD advisor, Mary Ellen Jones, a renowned biochemist who is notable for her discovery of carbamyl phosphate, a chemical substance that is key to the biosynthesis of both pyrimidine nucleotides, and arginine and urea. Jones, whom The New York Times called a “crucial researcher on DNA” and a foundational basic cancer researcher, had worked with eventual Nobel laureate Fritz Lipmann at Massachusetts General Hospital. 

When Chen arrived, while there were other Taiwanese students at USC, there were not many at the medical school. Chen says she bonded with a young female scientist and student from Hong Kong and with another female student who was Korean and Chinese, but who was born in America. Forming these friendships was crucial for blunting the isolation she could sometimes feel as a newcomer to America, particularly her connection with the American-born young woman: “She helped me a lot with getting used to the language,” and the culture, Chen says. “It was very hard to be so far away from my family and friends,” she adds. “It was the very first time I had left home. By coincidence, I had a very nice roommate who was not Chinese, but knew the Chinese language conversationally, so that was so lucky … I still have the letters that my parents wrote to me. I was the only girl, and the eldest child (Chen has three younger brothers), so it was hard for all of us.”

“Mostly, the culture I learned was in the lab,” Chen remembers. “I had to work a long day in the lab, and I knew it was such a great opportunity ­ — to go to seminars with professors to listen to speakers who had won, or would win, Nobel Prizes. My monthly living stipend was $300, so that had to stretch far. In my second year, more of my college friends had come to the USC and Caltech, and I began to have more interactions with other Taiwanese students who were studying here.”

Chen’s first scientific discovery at Jones’ laboratory was that the fourth enzyme of the pyrimidine biosynthesis, dihydroorotate dehydrogenase, is localized in the inner membrane of the mitochondria. As it more recently turned out, this enzyme plays dual roles not only for pyrimidine biosynthesis, but also for cellular redox homeostasis, and has been demonstrated to be an important target for the development of cancer treatments.

Coming to MIT

After receiving her degree, Chen received a postdoctoral fellowship to work at the Roche Institute of Molecular Biology, in New Jersey, for nine months. In 1979, she married Zong-Long Liau, who was then working at MIT Lincoln Laboratory, from where he also recently retired. She accepted a postdoctoral position to continue her scientific training and pursuit at the laboratory of Irving M. London at MIT, and Jane-Jane and Zong-Long have lived in the Boston area ever since, raising two sons.

Looking back at her career, Chen says she is most proud of “being an established woman scientist with decades of NIH findings, and for being a mother of two wonderful sons.” During her time at MIT and IMES, she has worked with many renowned scientists, including Gehrke and London, professor of biology at MIT, professor of medicine at Harvard Medical School (HMS), founding director of the Harvard-MIT Program in Health Sciences and Technology (HST), and a recognized expert in molecular regulation of hemoglobin synthesis. She says that she is also in debt to the colleagues and collaborators at HMS and Children’s Hospital Boston for their scientific interests and support at the time when her research branched into the field of hematology, far different from her expertise in biochemistry. All of them are HST-educated physician scientists, including Stuart H. Orkin, Nancy C. Andrews, Mark D. Fleming, and Vijay G. Sankaran.

“We will miss Dr. Chen’s sage counsel on all matters scientific and communal,” says Elazer R. Edelman, the Edward J. Poitras Professor in Medical Engineering and Science, and the director of the Center for Clinical and Translational Research (CCTR), who was the director of IMES when Chen retired in June. “For generations, she has been an inspiration and guide to generations of students and established leaders across multiple communities — a model for all.”

She says her life in retirement “is a work in progress” — but she is working on a scientific review article, so that she can have “my last words on the research topics of my lab for the past 40 years.” Chen is pondering writing a memoir “reflecting on the journey of my life thus far, from Taiwan to MIT.” She also plans to travel to Taiwan more frequently, to better nurture and treasure the relationships with her three younger brothers, one of whom lives in Los Angeles.

She says that in looking back, she is grateful to have participated in a special grant application that was awarded from the National Science Foundation, aimed at helping women scientists to get their careers back on track after having a family. And she says she also remembers the advice of a female scientist in Jones’ lab during her last year of graduate study, who had stepped back from her research for a while after having two children, “She was not happy that she had done that, and she told me: Never drop out, try to always keep your hands in the research, and the work. So that is what I did.”