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He's Seen the Light


  • Title: Head, Laboratory for Systems Biology, RIKEN
  • Education: PhD, University of Tokyo, 2004; MD, University of Tokyo, 2000
  • Recommended by: Hiroaki Kitano

Still early in his career, Hiroki Ueda has already worked on both sides of the public-sector/private-sector divide. He com-pleted both his MD and PhD at the University of Tokyo, and also spent time working as a researcher for Yamanouchi Pharmaceutical as well as Sony Computer Science Laboratories. That's not the only divide he has crossed: Ueda has worked both in computer science — training under Hiroaki Kitano — and in the wet lab, learning about “high-throughput 'omics” technologies during his time at the pharma firm, he says.

Today, he hangs his hat at RIKEN, where he serves as head of the Laboratory for Systems Biology and as manager of the institute's functional genomics division in the Center for Developmental Biology.

Born in Fukuoka, Japan, Ueda's current experimental focus is on circadian rhythms, and how to better understand them using systems biology approaches. “My favorite system is the mammalian internal clock,” he says. Using high-throughput tools, he can monitor as many as 4,600 samples at a time, which he does to trace the network composed of clock genes. Ueda has fine-tuned the mammalian cells he uses in these experiments by introducing a receptor for light recognition, so his cells have literally seen the light. “We can control the clock in the cell by using light,” he says. “We can control the cell state … and then derive the mechanisms, the logic of the clock, by perturbation.” The careful monitoring and rigorous controls he employs for this result in comprehensive and quantitative data, he adds.

Ueda recognizes that his work stands on the shoulders of all those scientists who slogged through genetic experiments long before “high-throughput” was part of the lexicon. In the days when his own teachers and mentors were in grad school, “the focus was to identify the important genes,” he says. Thanks to their work, he doesn't have to identify genes one at a time or seek out the most important genes — so his work can focus on examining these genes in large sets, or better understand them using quantitatively oriented research.

As his work evolves, Ueda says that he will incorporate developmental biology research as well, expecting to take on questions about how cells differentiate into various types of cells.

Looking ahead

A challenge facing current biology, Ueda says, is dealing with the question, “What is life?” He believes that “to address that question, we maybe need to create the cell.” That will require more than a little technology development, Ueda says, pointing to tools that would “produce functional proteins” as well as “manipulate the membrane and the membrane proteins” as just two examples of what would have to be invented before scientists can build their own cell from scratch.

Publications of note

Ueda has already contributed significantly to the scientific literature. Recently, he and John Hogenesch of the Scripps Research Institute were corresponding authors on a paper in Nature Genetics this year called “Requirement for feedback repression in mammalian circadian clock function.” In this paper, the authors discussed a molecular genetic screen they developed to identify mutants of two circadian transcriptional activators in mammalian cells, from which they demonstrate evidence that the mammalian clock function relies on transcriptional feedback.

In another paper entitled “An improved single-cell DNA amplification method for efficient high-density oligonucleotide microarray analysis” (published this year in Nucleic Acids Research), Ueda and colleagues describe a strategy that will globally amplify mRNAs from individual cells, using both PCR and linear amplification techniques, for analysis on an oligo-based array.               

The Scan

Study Tracks Off-Target Gene Edits Linked to Epigenetic Features

Using machine learning, researchers characterize in BMC Genomics the potential off-target effects of 19 computed or experimentally determined epigenetic features during CRISPR-Cas9 editing.

Coronary Artery Disease Risk Loci, Candidate Genes Identified in GWAS Meta-Analysis

A GWAS in Nature Genetics of nearly 1.4 million coronary artery disease cases and controls focused in on more than 200 candidate causal genes, including the cell motility-related myosin gene MYO9B.

Multiple Sclerosis Contributors Found in Proteome-Wide Association Study

With a combination of genome-wide association and brain proteome data, researchers in the Annals of Clinical and Translational Neurology tracked down dozens of potential multiple sclerosis risk proteins.

Quality Improvement Study Compares Molecular Tumor Boards, Central Consensus Recommendations

With 50 simulated cancer cases, researchers in JAMA Network Open compared molecular tumor board recommendations with central consensus plans at a dozen centers in Japan.