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Dr. Kazuko Nishikura: the RNA Explorer

August 8, 2019

Nishikura has been a pillar of Wistar science for the past 37 years with a career overlapping with the rise and expansion of the RNA biology field, which explores the alternative functions of RNA in the cell, besides carrying the genetic information from DNA to proteins. Her foray into research happened at a time when scientists were only beginning to understand the function of RNA and its molecular mechanisms; she would end up contributing fundamental knowledge to the field.

Nishikura discovered the process of RNA editing, an important mechanism of genetic regulation. Her scientific journey has taken her on to explore several aspects and functions of RNA editing and its interplay with other molecular pathways.

Passion for Science Sparks

Born and educated in Japan, Nishikura was encouraged by her high school science teacher who recognized her scientific talent. She obtained her PhD at Osaka University and pursued postdoctoral training at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, England, and Stanford University, two of the birthplaces of molecular biology.

Photos of those times hang from the wall in her office, memories of a cherished past, and portray some very famous scientists who left their mark in history and in Nishikura’s career: Nobel Prize winners Max Perutz, Ph.D., who discovered the structure of hemoglobin and was her doctoral thesis advisor, and John Gurdon, Ph.D., whose work on reprogramming mature cells to stem cells laid the foundation for major advances in cloning and stem cell research.

Nishikura spent two very formative years in his lab in Cambridge as a postdoctoral fellow, before moving to Stanford to work with another outstanding mentor, Roger Kornberg, Ph.D., also a Nobel laureate, who described how genetic information is passed from DNA to RNA.

Training with great minds of the time was the fertile scientific soil of her education as a scientist. Nishikura absorbed their intellectual curiosity and learned how to properly follow the scientific method as part of her training. “I consider myself very lucky for having had a chance to observe in person how those big scientists addressed important biological questions,” she said.

An Expanding Field of RNA Biology

RNA biology became Nishikura’s main research interest, which she has continued to cultivate throughout her career. It was a nascent field, rapidly expanding with fundamental discoveries, but so many questions were still unanswered.

However, at the time when she joined Wistar as an assistant professor, the Institute was mainly invested in cancer biology. Oncogenes were protagonists on the cancer research scene and Wistar scientists were pursuing seminal studies on chromosomal alterations, demonstrating their causative role in leukemia.

Nishikura was drawn into this line of investigation until the end of the 80s, when a paper by a former MRC colleague came out and described a mysterious biological activity that appeared to unwind double stranded RNA, which immediately caught Nishikura’s attention.

“I couldn’t resist looking into it,” she said. “For some time it was my pet project; no study section would believe in it and it was very risky too.”

That didn’t discourage her, and she kept pursuing the investigation with the resources she could spare from her other projects on oncogenes, which had much more success in securing funds for her lab.

“When you find something unusual you have to follow it,” said Nishikura. “Pursuing something unique will make you stand out from the crowd.”

This has been her favorite piece of advice for the young scientists training in her lab. “It’s sad and unfortunate that the current climate of high competition for funding pushes young independent investigators away from basic science. They hesitate to embark in risky projects, but these are often the source of breakthroughs.”

Nishikura considers herself fortunate to have had big opportunities that gave her the resources and the support to both follow her scientific interest and, at the same time, establish herself as a successful scientist, even though as a young investigator she wasn’t particularly focused on cultivating her academic career.

“I was only after my scientific questions and was content to just do my work and search for the answers,” she said. “In retrospect, I was probably naïve, even a little foolish. I didn’t worry much about problems and setbacks. This simplified my decision-making process and helped me stick to it.”

Thanks to her determination, Nishikura was able to secure her first grant on RNA editing when she found the gene responsible for the process. The rest is history.

“In the early 90s, RNA editing was a very new concept, with only two or three labs chasing it,” said Nishikura. “Today, it’s a large field with dozens of labs. It’s very satisfying to look back and see that I contributed to opening that path.”

The institutes where she trained put her on the right track and equipped her with a successful approach to science, then Wistar was the ideal landing ground to grow and establish herself. “Being at Wistar is a great asset, because of our collaborative environment and vocation of always being at the forefront of new trends and technologies,” said Nishikura. “It has helped substantially when I came across new themes and needed support to acquire different expertise or catch up with new develoments.”

Nishikura’s passion and curiosity are unchanged and she still finds great inspiration in science. In 2017, she successfully renewed a large federal grant that had continuously supported her work on RNA editing for 26 years, with a proposal to investigate a novel function she had recently discovered.

Outside the Lab

Meanwhile, when not in her lab, Nishikura cultivates other “side projects.”

She enjoys traveling the world, especially to places that are interesting from a biological point of view. She recently visited the Galapagos Islands and Antarctica and went on a safari in Africa. The exploration component of such trips resonates with her scientific mind.

“I love going to music concerts too,” she said. “Whenever I go to Europe for conferences, I try to catch the opera or a classic music concert.” That’s not to say that she doesn’t enjoy some good classic rock. “I’ve recently seen Eric Clapton, the Rolling Stones and Paul McCartney.”

At home, Nishikura is an experienced cook, specializing in many types of cuisine. She enjoys cooking for friends and neighbors. “I like cooking because I’m a foodie and because it takes method and creativity, just like science.”

These days, she’s been making a tasty and healthy beet salad. She will gladly share the recipe.

In the photo, Dr. Nishikura with the group of John Gurdon at the MRC Laboratory of Molecular Biology at the University of Cambridge, England. Courtesy of Dr. Nishikura.