UMDNJ Magazine - fall 2004 VOLUME 1 NUMBER 1

Walk away from a long conversation with Masayori Inouye, and playful is the first descriptive word that comes to mind about this scientist. Playful? That's what he is when he talks about his legendary work in genetics and biochemistry.

Masayori Inouye, PhD, chair of UMDNJ-Robert Wood Johnson Medical School's department of biochemistry.

In the science of genomics and the laboratory world of miniature RNA cellular movement, you don't expect to discover anything but sober, intellectual effort. Yet, evidence of Masayori Inouye's playful spirit abounds. Old jokes are framed on his wall, as well as a tongue-in-cheek submission by Inouye requesting to have his scientific work entered into The Guinness Book of World Records.

More important than the Guinness Book, Inouye's name appears on the ISI Highly Cited website, where he is acknowledged as one of the 250 most cited researchers in the world. The author of 571 manuscripts and nine books, including Histidine Kinases in Signal Transduction (November 2002), Inouye has made major contributions to science, including membrane biogenesis, structural and functional studies of histidine kinases, propeptide (intramolecular chaperone) mediated protein folding (related to Mad Cow disease), discovery of bacterial reverse transcriptases and multicopy single stranded DNA (msDNA) and the cold shock response and adaptation in E.coli. Although he is proud of his scientific publications, Inouye is equally proud of the publication of two books of poetry, which he authored in Japanese.

Though his parents were Japanese citizens, Inouye, who received his BA, MA and PhD from Osaka University in Japan, was actually born in China, where his family resided for 13 years. "My father was a scientist who traveled a lot and died when I was seven years old. His influence on my career choice was indirect. It was my mother who inspired me to go into science," Inouye recalls. Even now, however, his father's indirect presence is still there. Framed under glass on a bookshelf near the door are several black and white antique postcards sent home by his father from all over the world.

"There's the Chrysler Building in New York," he says. "And this one here was mailed in 1928. It depicts Madame Curie's laboratory in France." He pulls the card with a picture of the Eiffel Tower from beneath the glass so he can translate the Japanese characters. His father was there in Paris to observe the researchers trying to understand radioactivity. "See here, my father writes that he is impressed by the number of women working alongside men in the lab."

Inouye came to the United States in 1968 as a postdoctoral fellow at Princeton University. He decided to stay on, preferring the American research climate, which is less rigid than in Japan. From 1971 through 1975, he was an associate professor of biochemistry at the State University of New York, Stony Brook. He also served as chairman of the Department of Biochemistry at Stony Brook from 1975 through 1977, and as a professor of biochemistry from 1975 through 1986.

Inouye has been part of the RWJMS faculty since 1987. However, his ties to old friends have remained secure. Just three years ago, a Japanese friend, Ikunoshin Kato, PhD, President of Takara Bio., Inc., with whom he collaborated on a published paper in 1960, pledged $2 million to support the new Takara Bio. Endowed Chair in Bioinformatics at RWJMS. Over the years, the department of biochemistry at RWJMS has also welcomed many Japanese postdoctoral fellows, who have returned home and advanced into positions of power in business and research.

In the highlights from 100 years of science at the Cold Spring Harbor Laboratory in NY, world renowned for its cutting edge research, where one particular scientist is applauded for each particular year, Inouye holds the record for 1983 because of his discovery of micRNA. He points out this distinction with obvious pleasure.

Twenty years ago, Inouye and two collaborators (Takeshi Mizuno and Mei-Yin Chou) demonstrated that small RNA could inhibit 95 percent of the activity of a major protein in the E. coli bacteria. This breakthrough is still being built upon by today's genetic research pioneers, who have been using the notion of RNA activity to understand disease pathways and potential drug targets. Even though most recently published papers on RNA don't credit his finding, Inouye shrugs off any scientific slight. "That's just the way things go," he says.

The story behind the story of micRNA is a good one, he says. Other researchers had been discovering organic microRNA in nature. In fact, the letters m-i-c in micRNA technically stand for mRNAinterfering complementary RNA. Micro, small, or interfering RNA are miniature strands of ribonucleic acid, which control the chemical activities in a cell. "Depending on the field, they called it different names...sometimes miRNA, sometimes siRNA or RNAi," he explains.

Before Inouye's breakthrough in the mid-1980s, no one understood that small RNA represented a new mechanism for gene regulation or that RNAs could be used to protect living cells from viral (bacteriophage) infection. He's even more excited about recently finding a new enzyme, through which virtually every messenger RNA can be cut and targeted. "I am interested in how cells function and looking for applications in science.

"First published in 1984, our original work is considered one of the milestones in biotechnology, a classic paper on genetic engineering. Here it is," he says, pulling out a copy of "The Use of RNAs Complementary to Specific mRNAs to Regulate the Expression of Individual Bacterial Genes." Proudly, he also reaches for a large volume, Milestones in Biotechnology: Classic Papers on Genetic Engineering. "That was the first time it was shown how RNA functions in nature and then we immediately decided to construct an artificial micRNA system," Inouye says. "I've always worked in basic research but it is also a lot of fun looking for translational applications. This is the way my mind works. If you find something in nature, then why not try to do it artificially?"

There's more to this micRNA story, however. Inouye laughs as he moves toward his conclusion - a long-kept secret literary twist. "Mizuno proposed calling it micRNA not just because it was messenger interfering complementary but because the m stands for Mizuno, the i stands for Inouye and the c for Chou. No one knows this."