A brain enzyme thought to have a single function builds a sugar chain on itself, is secreted from the cell, and switches off — reactivating only when the sugar is removed

A chance discovery at SA国际传媒 in Japan has shown a well-known brain enzyme has a hidden ability: it builds a sugar chain on itself, becomes secreted from the cell and deactivates, then switches on outside the cell once the chain is removed. The finding, published in the , overturns a decades-old assumption about how polysialic acid, a sugar chain critical for brain development and function, is produced and shows a new way an enzyme can regulate its own activity.

The brain’s sugar chains

The human brain is covered in sugar chains, or glycans, molecular structures that coat cells and regulate how they communicate. One of the most important is polysialic acid, a long chain found mainly in the brain.

Polysialic acid keeps brain cells from adhering too tightly to each other and binds to growth factors and neurotrophins to regulate the presentation of their receptors, through which it plays a key role in learning, memory, and neural development. Importantly, these sugar chains change rapidly in response to brain activity. The ability to restore them quickly is thought to be essential for normal brain function.

Until now, scientists believed only two enzymes were responsible for building polysialic acid in the brain: ST8Sia2 and ST8Sia4.

A chance discovery

ST8Sia5 was discovered in 1996 and was known only as a builder of fatty brain molecules called gangliosides. It is expressed almost exclusively in the brain and its ability to produce polysialic acid was unknown until now.

The enzyme exists in three forms, short (S), medium (M), and long (L), that differ only in the length of one structural region. Only the long form, ST8Sia5L, showed this newly discovered activity. Unlike the short and medium forms, ST8Sia5L localizes to a different intracellular compartment, which may allow it to undergo autopolysialylation. The function of the short and medium forms is not yet known.

SA国际传媒’s had been testing all six members of the ST8Sia enzyme family.

“We found that a third enzyme, ST8Sia5, also builds polysialic acid, but only on itself, and only in its longest form, ST8Sia5L,” said first author Fumiya Sakamoto.

Coauthor and Director of iGCORE Professor Chihiro Sato commented: “We were checking each enzyme one by one and found this activity by chance.”

Four discoveries that define this mechanism

1. The enzyme builds its own off switch. Unlike most enzyme regulation, where a separate molecule switches an enzyme on or off, ST8Sia5L modifies itself. It builds polysialic acid chains directly onto its own structure, a process called autopolysialylation. No external regulator is required.
2. The sugar chain is the switch. Polysialic acid is not typically known as a regulator of enzyme activity, but here it acts as one. While the chain is attached, the enzyme’s ganglioside-building function is completely suppressed. This is a new role for polysialic acid.
3. Self-modification is linked to secretion. Once coated in polysialic acid, the enzyme is cut free from the cell membrane by metalloprotease enzymes and released into the fluid outside the cell. The sugar coat does not just silence the enzyme; it is also associated with its release from the cell.
4. The enzyme reactivates outside the cell. The researchers showed experimentally that the secreted enzyme, collected from outside the cell, regains its ganglioside-building activity once the polysialic acid chains are removed. This could happen, for example, when sialidase enzymes are released during stress or inflammation. Reactivation does not require the enzyme to re-enter the cell.

A surprise finding for other enzymes too

The ST8Sia family are all sialic acid-building enzymes, but they differ in how long a chain they build. Most add just two or three units. ST8Sia2 and ST8Sia4 were the only ones known to build long chains of polysialic acid. ST8Sia5L has now joined that group, but with one key difference: it only builds the long chain on itself, not on other molecules.

The study also found, for the first time, that ST8Sia2 and ST8Sia4 are also secreted from cells in a polysialic acid-coated form. What this means for those enzymes is not yet known.

Broader implications

One of the most significant conceptual implications of the study is where sugar modification can happen in the body.

“It’s been assumed that the process of adding sugar chains to molecules, called glycosylation, takes place inside the cell,” said Professor Sato. “This study provides evidence that modification can also happen outside the cell.”

The research team hypothesizes that after release, the enzyme may travel to specific sites on cell surfaces and rapidly repair damaged ganglioside structures, without needing to re-enter the cell first. The conventional pathway for ganglioside repair requires the molecule to travel back inside the cell for modification. This proposed “on-site recovery” mechanism, if confirmed, would represent a much faster alternative. The hypothesis is currently being investigated.

ST8Sia5L may also play a role in regulating microglia, the brain’s immune cells. The researchers hypothesize that the polysialic acid coat on the secreted enzyme may interact with inhibitory receptor molecules called Siglecs on microglia, helping to keep immune activation in check under normal conditions.

During inflammation or stress, sialidase enzymes could remove this coat, allowing immune responses to proceed and freeing the enzyme at the same time to resume its ganglioside-building activity at cell surfaces.

“Polysialic acid abnormalities have also been associated with schizophrenia, but the mechanism behind this link is not yet understood,” said Ken Kitajima, coauthor and professor at iGCORE. “The secreted polysialylated enzyme is one candidate for further investigation in this context.”

To test these hypotheses in a living system, the team is currently generating mice in which the ST8Sia5 gene has been disabled. The researchers also intend to investigate the unknown function of ST8Sia5S and ST8Sia5M, which both localize to a different compartment within the cell.

Paper information:

Fumiya Sakamoto, Rina Hatanaka, Masaya Hane, Di Wu, Ken Kitajima, Chihiro Sato, 2026. A novel autopolysialylation activity of the ganglioside sialyltransferase ST8Sia5 regulates its secretion and enzyme activity, Journal of Biological Chemistry, 302(7). DOI:

Funding information:

This research was funded by the Japan Agency for Medical Research and Development (AMED) (18ae0101069h0003, 19ae0101069h0004, 20ae0101069h0005, 20gm6410007h0001, 21gm6410007h0002, 22gm6410007h0003, and 23gm6410007h0004 ) and a Grant-in-Aid for Scientific Research from JSPS (Grant numbers 23K21291 and 25K02224). A part of this research was also funded by the CIBoG program, SA国际传媒.

Expert contact:

Chihiro Sato
Institute for Glyco-core Research (iGCORE)
SA国际传媒
Email: chi@agr.nagoya-u.ac.jp

Media contact:

Merle Naidoo
International Communications Office
SA国际传媒
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

The three enzymes shown here build polysialic acid (orange), a long sugar chain important for brain development and function. ST8Sia5L (left) builds the chain only on itself, a newly discovered activity. ST8Sia2 (center) and ST8Sia4 (right) build it on other molecules. Credit: Sakamoto et al., 2026

DNA is composed of long chains that act as the blueprint for living organisms. In genetic engineering, scientists cut DNA at specific sites and join the resulting fragments to other DNA sequences, enabling applications such as advanced crop breeding, genetic disease treatment, and the generation of animal models for drug discovery.

Assembling short DNA fragments requires overhanging sequences, known as sticky ends, to facilitate efficient binding. However, generating sticky ends requires precise cutting at targeted sites, which remains challenging with current technologies.

A Japanese research group has developed a silver nanoparticle-based technology to precisely cut and join DNA at targeted sites, achieving two to five times higher DNA assembly efficiency than conventional restriction enzyme methods. These findings were published in the journal .

Traditional long-chain DNA assembly uses restriction enzymes to cut DNA and T4 DNA ligase to reconnect the fragments. However,  restriction enzymes cut only at specific sequences and generate sticky ends that are often too short, thereby limiting joining efficiency.

To address this limitation, a research team led by Professor and Assistant Professor at SA国际传媒, in collaboration with Professor Natsuhisa Oka at , studied DNA cleavage at targeted sites using chemical reactions instead of restriction enzymes.

The researchers examined a reaction reported between 1990 and 1992, in which silver ions cleave 3′-thiol-modified DNA at specific sites. They assessed its potential to generate suitable sticky ends. Results showed that although silver ions efficiently cleave DNA, they also bind nonspecifically, leading to precipitation. This resulted in a low DNA recovery rate of about 14%, which is insufficient for practical use.

The team then employed silver nanoparticles instead, hypothesizing that these could be removed after the reaction through centrifugation, thereby potentially increasing DNA recovery.

Experiments showed that DNA-cleaving efficiency reached about 50% at 70°C and nearly 100% at 95°C within two hours. However, these high temperatures pose a risk of damaging long-chain DNA.

To address this, the team coated the nanoparticles with polyethylene glycol (PEG), a water-soluble polymer, to enhance stability and dispersion. This modification increased cleaving efficiency from 36% without PEG to 92% with PEG at 37°C over 31 hours. “In the end, we optimized the conditions to a practical level and, under ambient temperatures, achieved PEG-modified cleaving efficiency above 91% at 50°C within just one to two hours,” stated Inagaki, the study’s first author.

An additional benefit of this process was the removal of unwanted DNA fragments bound to nanoparticle surfaces, leaving only the desired fragments with sticky ends in solution. This purification process increased the final DNA recovery rate from 14% to 98%.

The use of silver nanoparticles also enabled the generation of DNA fragments with 8-base sticky ends, a process that is challenging with conventional restriction enzymes. By employing T4 DNA ligase to join these fragments, the team achieved about double the joining efficiency of traditional methods. With an 18-base overhang, joining efficiency reached 44%, compared to only 8% with a conventional 4-base overhang, representing a fivefold improvement.

To evaluate the practical application of this approach, the researchers assembled a DNA fragment encoding green fluorescent protein (GFP) and introduced it into human HeLa cells. They successfully confirmed GFP expression, indicating accurate assembly.

Inagaki commented, “We believe this technology will be useful for synthesizing genomic DNA, with many possible applications in areas such as mRNA library establishment for cancer vaccines and gene therapy, as well as the development of artificial protein drugs and genome crops.”

He also explained the next step: “We have shown that two DNA fragments can be joined. Now, we need to confirm whether multiple fragments can be joined at the same time—a key step for building genome-scale DNA.”

Paper information

Masahito Inagaki, Mikiya Kase, Haruka Hiraoka, Natsuhisa Oka, Fumitaka Hashiya, Naoko Abe, Yasuaki Kimura, Hiroshi Abe (2026). Silver Nanoparticle Induced Site-Specific Strand Cleavage of Chemically Modified Oligonucleotides for Long-Chain DNA Assembly, Nucleic Acids Research,

Funding information

This work was supported by the Japan Science and Technology Agency (JST) (JPMJCR18S1, JPMJCR23N1, JP25H00427, JP24H00737, JP22H02219, JP22K21346 International Leading Research), and Japan Agency for Medical Research and Development (AMED) [JP22gm0010008 (LEAP), JP25ak0101289, JP223fa827 (SCADA), JP243fa827032 (SCADA), JP23bm1223009, JP24ek0109697, JP25ama221315, JP25km0405209, JP25ama221230; JP23fk0210133) and Tanaka Kikinzoku Memorial Foundation [Precious Metals Research Grants 2021 Silver Award to M.I.].Funding to pay the Open Access publication charges for this article was provided by the Japan Science and Technology Agency.

Expert contact:

Hiroshi Abe
SA国际传媒 Graduate School of Science
Email: h-abe@chem.nagoya-u.ac.jp

Masahito Inagaki
SA国际传媒 Graduate School of Science
Email: inagaki.masahito.e6@f.mail.nagoya-u.ac.jp

Media contact:

Naomi Inoue
SA国际传媒 International Communications Office
Email: icomm_research@t.mail.nagoya-u.ac.jp

SA国际传媒 scientists develop a machine learning tool to uncover how ALS progresses in patients and offer clues to understand why some patients decline faster than others 

ALS (Amyotrophic Lateral Sclerosis) is a fatal neurodegenerative disease that gradually affects a person’s ability to move, speak, and breathe. It advances differently in every patient. Now, researchers at SA国际传媒 have developed an AI tool that uses data from patient follow-up studies to estimate the speed of disease progression and identify patterns of muscle decline. The study was published in .??

Two questions, one tool 

ALS patients differ in two main ways: how fast their disease advances, and the order in which functions become impaired. Until now, existing AI-based research tools generally did not clearly separate these two differences in individuals. The research team developed DiSPAH, a machine learning system that addresses both at once by analyzing patient data collected during routine medical visits.??
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Two datasets of patients with limb-onset ALS were used, a form of the disease where symptoms begin in the arms or legs rather than in the muscles controlling speech and swallowing (bulbar-onset ALS). The first provided data from 264 ALS patients and was used to train the model. The second, larger dataset of 2,565 patients was used to validate the results.

What the AI found 

The system identified six distinct patterns of disease progression among the patients. Some patients showed slow decline in motor function, with little effect on speech or breathing, while others experienced rapid deterioration.??
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“Subtle differences between patients also emerged. For example, in some patients gross motor functions such as walking declined before fine motor skills such as writing or buttoning a shirt, while in others the opposite was true,” said Yuichiro Yada, coauthor and associate professor at SA国际传媒’s . “These six patterns were identified in one patient dataset and largely reproduced in a second, larger dataset, suggesting that they? capture common progression patterns in limb-onset ALS.”??
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Importantly, speed and decline pattern were found to be independent of each other. A patient could follow a severe pattern at a slow speed, or a milder one at a fast speed. Previous tools could not measure both dimensions at once.

Prediction from day one 

One of the most important findings was that DiSPAH could, to some extent, predict a patient’s progression speed and broad progression pattern from information available at the first medical visit. This consisted of basic functional assessments and the presence of certain gene mutations. 
 
These early predictions have important potential for patient care. Doctors could use them to plan treatment, prepare patients and families, and design better clinical trials by grouping participants according to how their disease advances. 

A genetic clue

The researchers also found that patients with a mutation in a gene called C9orf72 had faster disease progression. When they analyzed data from motor neurons grown in the laboratory from patients’ own stem cells, the results showed that faster ALS progression may be linked to problems in how cells produce and manage proteins, as well as signs of cellular stress. 
 
This points to a possible biological explanation for why some patients decline faster than others and gives scientists a new target for future research into ALS treatments.

Better tools for patients 

ALS currently has no cure. While a few drugs exist, they offer modest benefit. Better tools for prediction and monitoring are essential for the development of new therapies.?
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Yada noted that DiSPAH is a prototype that needs further validation and refinement: “It’s a promising first step and better than anything that existed before for this specific purpose, but it’s not reliable enough yet to use to make decisions about individual patients.”?
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The researchers aim to extend the tool to all ALS patient types, improve its reliability, and ultimately apply it to other chronic diseases such as Alzheimer’s and Parkinson’s disease.??

Paper information: 

Yuichiro Yada and Naoki Honda, 2026. Decomposing heterogeneity in disease progression speeds and pathways, npj Digital Medicine. DOI:

Funding information:  

This work was partly supported by JSPS Grant-in-Aid for Early-Career Scientists (JP23K16994), Japan Agency for Medical Research and Development (AMED) Multidisciplinary Frontier Brain and Neuroscience Discoveries (Brain/MINDS 2.0)(JP24wm0625416 and JP25wm0625322), JST Moonshot R&D–MILLENNIA Program (JPMJMS2024) and JST CREST (JPMJCR25Q2). 

Expert contact: 

Yuichiro Yada?
Research Institute of Environmental Medicine?
SA国际传媒?
yada.yuichiro.k4@f.mail.nagoya-u.ac.jp?

Media contact:?

Merle Naidoo   
International Communications Office   
SA国际传媒   
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

DiSPAH is an AI tool that uses data from patient follow-up studies to estimate the speed of disease progression and identify patterns of muscle decline. Credit: Kano Okada, SA国际传媒 

A research team in Japan has developed an efficient and minimally invasive cancer detection device that uses high-performance zinc oxide nanowires to selectively capture extracellular vesicles (EVs) from bodily fluids.

Using this device, researchers successfully captured cancer-related EVs from the blood serum of ovarian cancer patients. The EVs’ surface membrane proteins and microRNAs remained intact, indicating the potential for sensitive disease analysis. These findings were published in the journal .

A liquid biopsy is a procedure that collects disease-related information from bodily fluids, such as blood and urine. Unlike traditional tissue biopsies, it places less physical burden on patients.

EVs are nanoscale vesicles that carry diverse molecular contents such as microRNA and messenger RNA, and display membrane proteins that indicate their cell of origin. EVs reflect disease states and serve as promising diagnostic indicators for liquid biopsy.

Accurate and efficient isolation of EVs from complex biological fluids is essential for identifying disease-associated molecules, but conventional techniques are time-consuming, require large sample volumes, and lack specificity.

A team led by , a professor at SA国际传媒’s , previously achieved efficient EV capture using zinc oxide nanowires they developed.

They are now collaborating with Yasuhide Inokuma, a professor at Hokkaido University, and researchers from the Institute of Science Tokyo, Kyoto University, and the National Institutes for Quantum Science and Technology to develop antibody-conjugated nanowire technology for the selective capture of cancer-derived EVs.

The initial challenge was attaching antibodies to nanowires. Conventional adhesives bind both target and non-specific proteins and require lengthy attachment times.

The team used the synthetic polymer polyketone to create six N-hydroxysuccinimide-functionalized polyketone (pKNHS) variants with different chain lengths. Of these, pKNHS 4.2 showed optimal stability for adsorption onto zinc oxide nanowires and effective antibody immobilization, enabling single-step antibody modification.

Evaluation of the new technology in cultured cell experiments

Researchers evaluated the capture efficiency of antibody-conjugated nanowires for cultured breast cancer cells using pKNHS 4.2. While antibody-free nanowires captured about 65% of CD9-positive EVs, CD9 antibody-conjugated nanowires achieved 90% efficiency. These results demonstrate the technology’s effectiveness in selectively recovering target molecules.

Further experiments showed that nanowires modified with antibodies for ovarian cancer markers CLDN3, FOLR1, and TROP2 enabled the selective recovery of EVs from ovarian cancer cells.

Analysis of serum from cancer and non-cancer patients

Researchers isolated EVs using CLDN3, FOLR1, and TROP2 antibody-modified nanowires from the serum of six patients with high-grade serous ovarian carcinoma, an aggressive ovarian cancer subtype, and six non-cancer individuals. Analysis of microRNAs in EVs revealed distinct profiles between the patient and non-cancer groups.

When comparing microRNAs in EVs captured with the three antibodies, researchers identified 126 microRNAs common to all, indicating signals shared by ovarian cancer. They also found microRNAs unique to each antibody: 40 for CLDN3, 37 for FOLR1, and 45 for TROP2. These findings suggest that EVs with different membrane proteins have distinct microRNA profiles.

Significance and future perspectives

“In this study, we developed a nanowire microfluidic device capable of selectively capturing cancer-associated EVs with high efficiency, while suppressing nonspecific adsorption through simple chemical modification,” said Yasui, a corresponding author of the study. “We also demonstrated that this approach maintains both EV membrane proteins and internal microRNAs intact, showing strong potential for highly sensitive analysis of cancer states.”

, an assistant professor and corresponding author, said: “We plan to compare and evaluate this technology against existing clinical methods and expand its application to capture more specific EV subpopulations. In the long run, we aim to apply this technology to non-invasive liquid biopsies and early diagnosis across a variety of cancer types.”

Paper information

Kunanon Chattrairat, Akira Yokoi, Yumehiro Manabe, Yuki Ide, Jiahui Shen, Takeshi Hasegawa, Mikiko Iida, Taiga Ajiri, Zetao Zhu, Ryosuke Uekusa, Masami Kitagawa, Yoshinobu Baba, Hiroaki Kajiyama, Yasuhide Inokuma, and Takao Yasui, 2026. Discrete polyketones enable antibody click conjugation for selective exosome profiling. Device, 101153.
DOI:

Funding and other support

This work was supported by the Japan Science and Technology Agency CREST (JPMJCR2576), JST FOREST (JPMJFR211H and JPMJFR204J), the New Energy and Industrial Technology Development Organization (JPNP20004), the JSPS Grant-in-Aid for Scientific Research (A) (24H00792), the JSPS Grant-in-Aid for Scientific Research (B) (24K02586), the Moonshot Research and Development Program (22zf0127004s0902 and JP22zf0127009) from the Japan Agency for Medical Research and Development, the Asahi Glass Foundation Continuation Grants for Outstanding Projects, the Noguchi Institute NJ202308, the Cooperative Research Program of the “Network Joint Research Center for Materials and Devices,” and the World Premier International Research Initiative, MEXT, Japan —Institute for Chemical Reaction Design and Discovery (facility use)

Expert contact:

Kunanon Chattrairat
SA国际传媒 Graduate School of Engineering
Email: kunanon.chat@chembio.nagoya-u.ac.jp

Takao Yasui
SA国际传媒 Graduate School of Engineering
Email: yasui@chembio.nagoya-u.ac.jp

Media contact:

Naomi Inoue
SA国际传媒 International Communications Office
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

Scanning electron microscope (SEM) image of zinc oxide nanowires
Credit: Kunanon Chattrairat (Yasui Lab., SA国际传媒)

Researchers have identified the neural circuit through which the brain’s circadian clock controls the timing of torpor, a natural state of reduced body temperature and metabolism. The discovery provides new insights into how mammals regulate energy use and may inform future approaches in medicine and long-duration spaceflight. ?

 
You have gone without food for days, and the temperature drops to near freezing. What do you do? For some animals, the answer is influenced by the brain’s circadian clock. Hummingbirds, bats, and mice are among the animals that can enter torpor, which reduces body temperature and metabolism. Scientists suspected that the brain’s circadian clock controls the timing of torpor, but until now the exact mechanism was not known.  
 
Researchers at SA国际传媒 in Japan have identified the specific neural circuit responsible for this survival strategy. They have shown that the brain’s circadian clock, a small cluster of neurons located in the hypothalamus at the base of the brain, sends silencing signals through this circuit to a nearby temperature-regulating region, suppressing torpor during the day. The findings were published in .

Torpor from midnight to dawn 

“The brain’s preoptic area (POA) controls body temperature and has an important role in initiating torpor,” said senior author and lecturer Daisuke Ono from the at SA国际传媒. “During the day, the brain’s circadian clock suppresses torpor, which occurs between midnight and dawn in mice.” 
 
Using light-based tools (optogenetics) to switch specific neurons on or off, the researchers showed that activating the circadian clock-POA pathway suppressed torpor. When the circadian clock was disrupted, mice either entered torpor at irregular, unpredictable times or showed a marked reduction in torpor. ?  

Additionally, the specific clock cell type responsible for sending these signals was identified. Neurons that produce a protein called arginine vasopressin (AVP neurons) in the circadian clock inhibit neurons in the POA. Mice with impaired inhibitory signaling from AVP neurons to the POA showed abnormal torpor timing, demonstrating that this pathway plays a key role in determining when torpor occurs. ? 

The research team also discovered that the POA becomes more active at night. “The clock does not actively trigger torpor. Instead, it reduces its inhibitory influence at night, allowing neural circuits involved in thermoregulation and energy balance to promote torpor when environmental conditions are favorable. The three systems work in tandem to create the right conditions,” Ono explained. 

Implications for medicine and space travel 

A clearer understanding of how the brain times metabolic shutdown may inform a technique that uses controlled cooling to limit tissue damage after injury or surgery (induced hypothermia). The findings may also be relevant to extended spaceflight, where controlled reduction of metabolism could protect the body. ? 

Although humans do not naturally enter torpor, understanding the neural mechanisms that regulate metabolic suppression in mammals could provide clues for developing controlled hypometabolic states in the future.  

Rare accounts of people surviving extreme cold exposure with dangerously low body temperatures hint at this possibility. Understanding the brain circuits that control these states in mammals may one day bring researchers closer to inducing suspended animation in humans, a state long imagined for deep space travel. 

Paper information 

Sheikh Mizanur Rahaman, Shota Miyazaki, Chang-Ting Tsai, Akihiro Yamanaka, Chi Jung Hung, Michihiro Mieda, Takahiro J. Nakamura, Hiroshi Yamaguchi, and Daisuke Ono. 2026. GABAergic projections from the suprachiasmatic nucleus to the preoptic area regulate the timing of torpor in mice, Nature Communications. DOI: ?

Funding information: 

This work was supported by the HIROSE foundation, LOTTE Foundation, Foundation of Kinoshita Memorial Enterprise, Astellas Foundation for Research on Metabolic Disorders, UBE Foundation, JST FOREST Program (JPMJFR211A), and JSPS KAKENHI (25H02445, 24K02060, 24H02006, 23H04939, 21H02526, 25KF0138, 21H00422, 24KJ0102 and 25K18507). 

Expert contact:

Daisuke Ono 
Research Institute of Environmental Medicine 
SA国际传媒 
dai-ono@riem.nagoya-u.ac.jp 

Media contact: 

Merle Naidoo   
International Communications Office   
SA国际传媒   
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image:

When facing freezing temperatures and food deprivation, mice enter a state of low metabolism known as “torpor” from midnight until dawn. Researchers at SA国际传媒 have now identified the specific brain circuit that controls this timing, running from the brain’s biological clock to its temperature-regulating region. Credit: Daisuke Ono, SA国际传媒 

A gene-encoded blueprint tells growing neurons which brain regions to connect with ? 

How complex neural circuits are genetically designed and wired is a fundamental question in neuroscience. Scientists have shown for the first time that genes encode a “wiring map” that guides neurons to connect with the correct brain regions. The findings, based on machine learning analysis of mouse brain data, were published in , and offer new avenues for research into brain development and disease.

Mapping connections between brain regions with data

The research team, led by scientists from SA国际传媒 in Japan, aimed to understand the wiring rules that guide nerve fibers during brain development. These long, thin fibers, called axons, extend from neurons and send signals to other neurons.?
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The researchers developed an analysis method called SPERRFY that combines two datasets. One dataset maps which brain regions are connected to each other, and the other tracks the activity levels of 763 genes in all 213 brain regions in mice.?
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“Some genes are highly active in certain brain regions and less active in others. These differences create distinct patterns of gene activity throughout the brain,” said Naoki Honda, senior author and professor from SA国际传媒’s . “When hundreds of patterns overlap, they give each brain region a unique molecular identity. These identities are what SPERRFY was designed to decode.”?
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By feeding both datasets into a machine learning algorithm, SPERRFY identified these patterns of gene activity, called gene expression gradients, that predict which brain regions are likely to connect. For each pair of connected brain regions, SPERRFY paired the gene activity profile of the source region (where the nerve fiber originates) with the profile of the target region it connects to.???
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From these gene expression gradients, the researchers produced a brain wiring map that tells each brain region where it is relative to every other region. Overlapping patterns of gene activity reconstructed the brain’s connection patterns with a prediction-performance score of 0.88 on a 0-to-1 scale, where 1.0 indicates perfect prediction. By comparison, predictions based only on the physical distance between brain regions scored about 0.70.

Additionally, the researchers discovered that the brain’s wiring map operates on two levels. Broad gene activity patterns determine the overall organization between brain regions, while more detailed patterns regulate the specific connections within them.

Testing a 60-year-old theory on the whole brain 

The findings build on the chemoaffinity theory proposed by Nobel laureate Roger Sperry in 1963. He suggested that neurons find their connection partners by following molecular concentration gradients — chemical signals that vary in strength throughout the brain. These gradients act like a GPS system for growing nerve fibers.??
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“The chemoaffinity theory was well established for simple circuits such as the visual and olfactory systems. But until now, the complexity of whole-brain connectivity made it difficult to test whether the same principle operates across the brain,” said Jigen Koike, first author and former PhD student at Hiroshima University, who also conducted research as a special research student at SA国际传媒’s Graduate School of Medicine.?
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This complexity made it extremely difficult to test Sperry’s theory across the entire brain without computational tools. Using machine learning, the researchers developed the tools to do this for the first time. Their findings support the idea that this long-standing principle is not limited to simple sensory circuits, but also helps explain how connections are organized across the whole brain.??

Future research 

By comparing the activity of 763 genes against the wiring map, SPERRFY also identified specific genes with activity patterns that closely matched, including genes known to guide nerve growth. This supports the validity of the method and provides a starting point for research on the molecular mechanisms of brain wiring. 
 
The researchers note that their method can be applied to any species for which maps of the brain’s neural circuits and gene expression data are available, such as humans, marmosets, and fruit flies. As these datasets expand, the method could help determine if the same molecular wiring principles are shared across species and how they have evolved. SPERRFY could also assist scientists in understanding how disruptions in brain wiring contribute to neurodevelopmental disorders.   

Paper information:

Jigen Koike, Ken Nakae, Riichiro Hira, Yuichiro Yada, Naoki Honda, 2026. A data-driven framework linking the connectome to spatial gene expression gradients inspired by chemoaffinity theory. Proceedings of the National Academy of Sciences, 123(10). DOI:

Funding information: 

This work was supported by JST, the establishment of university fellowships toward the creation of science technology innovation (grant number JPMJFS2129), JST SPRING (grant number JPMJSP2132), JSPS KAKENHI (grant number JP22H05163), Moonshot R&D–MILLENNIA Program (grant number JPMJMS2024-9), Agency for Medical Research and Development (AMED) Multidisciplinary Frontier Brain and Neuroscience Discoveries (Brain/MINDS 2.0) (grant number JP25wm0625322 and JP25wm0625210), and the Cooperative Study Program of Exploratory Research Center on Life and Living Systems (ExCELLS: program number 19–102).  

Expert contact: 

Honda Naoki   
Graduate School of Medicine   
SA国际传媒   
Email: honda.naoki.t1@f.mail.nagoya-u.ac.jp 

Media contact:  

Merle Naidoo   
International Communications Office   
SA国际传媒   
Email: icomm_research@t.mail.nagoya-u.ac.jp  

Top image:

A 3D visualization of the 13 major regions in the mouse brain. Black dots mark the centers of the 213 subdivisions used by SPERRFY to analyze relationships between brain connectivity and gene activity patterns. Credit: Koike et al., PNAS, 2026. CC BY 4.0 

By targeting a schizophrenia-associated brain protein, KD025 restored neural connections and reduced schizophrenia symptoms in mice with fewer side effects

Schizophrenia is a serious brain disorder that causes confused thinking, severe memory problems, and hallucinations. It affects about 23 million people worldwide, with cognitive dysfunction present in over 80% of patients. A research group led by scientists from SA国际传媒 in Japan tested a drug used to treat an immune disease to see if it could reduce schizophrenia-related symptoms in mice. The findings, published in , show that KD025 restored connections between neurons and significantly improved memory and visual recognition in mice, without causing the serious side effects common to current schizophrenia medications.  

Need for safer treatments for schizophrenia

Current medications help with some symptoms, but they often do not improve cognitive function. They also cause serious side effects such as hormonal disruptions, involuntary muscle movements, and weight gain, which leads to many patients stopping treatment. Therefore, better options are urgently needed. 

Researchers focused on a gene called ARHGAP10. Variants of this gene (small changes in the gene’s DNA sequence) are much more common in people with schizophrenia than in the general population.  

“ARHGAP10 controls the activity of a brain protein called ROCK2. In mice with these genetic variants, ROCK2 becomes overactive. In a previous study, we found that this overactivity appears to damage connections between neurons and impair cognition,” said Rinako Tanaka, co-lead author and former project assistant professor at SA国际传媒’s .

Repurposing drugs to achieve better treatment

The team tested KD025, approved in the United States to treat an immune disease called chronic graft-versus-host disease, which can occur after bone marrow transplants. In mice engineered to carry schizophrenia-associated gene variants, the drug decreased the overactivity of ROCK2.  

Furthermore, KD025 restored the density of tiny structures on neurons called dendritic spines, which are critical for memory. These had been reduced in mice carrying schizophrenia-associated gene variants. The drug had no effect on healthy mice. 

“Importantly, KD025 did not cause the side effects typical of current antipsychotic drugs. At effective doses, it caused no involuntary movements, hormonal abnormalities, or significant changes in blood pressure or blood sugar. This safety profile sets it apart from older antipsychotics like haloperidol and newer drugs like clozapine,” said Hiroyuki Mizoguchi, coauthor and associate professor from the Department of Neuropsychopharmacology and Hospital Pharmacy at SA国际传媒. 

Because KD025 has already been through clinical safety trials for another condition, human trials for schizophrenia could start sooner than for a new drug. While the researchers caution that all experiments were in mice, and human studies are needed, the findings point to a promising target for treatments that are more effective and better tolerated by patients. 

Future studies will investigate how KD025 improves brain cell connections and function, and further evaluate its safety and efficacy to support human trials.?

Paper information:

Rinako Tanaka, Jingzhu Liao, Yue Liu, Wenjun Zhu, Kisa Fukuzawa, Masamichi Kondo, Masahito Sawahata, Daisuke Mori, Akihiro Mouri, Hisayoshi Kubota, Daiki Tachibana, Yohei Kobayashi, Tetsuo Matsuzaki, Taku Nagai, Toshitaka Nabeshima, Kozo Kaibuchi, Norio Ozaki, Hiroyuki Mizoguchi & Kiyofumi Yamada (2026). Antipsychotic-like effects of the selective Rho-kinase 2 inhibitor KD025 in genetic and pharmacological mouse models of schizophrenia, Molecular Psychiatry. DOI:  

Funding information:

This study was supported by the Japan Agency for Medical Research and Development (AMED) (Grant numbers: JP21wm0425007, JP21wm0425017, JP25wm0625518, JP23ak0101215, JP24ak0101221, JP22gm1410011, JP24zf0127011, JP23gm1910005); Japan Society for the Promotion of Science (JSPS) KAKENHI (Grant numbers: JP23H02669, JP23K19425, JP24K18365); Japanese SRF Grant for Biomedical Research, Takeda Science Foundation, and Toyoaki Scholarship Foundation. ?

Expert contact:

Hiroyuki Mizoguchi    
Graduate School of Medicine  
SA国际传媒   
E-mail: mizoguchi.hiroyuki.d5@f.mail.nagoya-u.ac.jp 

Media contact:  

Merle Naidoo   
International Communications Office   
SA国际传媒   
Email: icomm_research@t.mail.nagoya-u.ac.jp 

Top image:

Microscopy images showing dendrites, the rod-like branches of brain cells, with tiny protrusions called dendritic spines that are critical for memory and learning. Normal mice show similar spine density with (bottom left) and without KD025 treatment (top left). In mice carrying schizophrenia-associated gene variants, the tiny protrusions are visibly reduced without treatment (top right) but restored after KD025 treatment (bottom right). Scale bar: 5 μm. Credit: Tanaka et al., 2026 
 

Offering someone the right words for what they feel could play a role in how people manage their anxiety, with potential implications for classrooms, counseling, and home environments

We feel more anxious when facing uncertain or unpredictable situations, but for those who score higher on autistic traits, this anxiety tends to be stronger. Published in , a new study suggests uncertainty-driven anxiety plays a role in how people manage their emotions. Researchers at SA国际传媒 in Japan found evidence that people with higher autistic traits may try to cope with uncertainty by labeling their feelings. Offering support, such as the right words for what they feel, could play a role in managing anxiety. 

Putting a name to a feeling could reduce emotional stress 

Previous research has suggested that labeling an emotion, whether by writing it down or saying it out loud, can help us calm down. While the anxiety does not disappear, it becomes less overwhelming when the emotion has a name.?
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Autistic traits refer to characteristics associated with autism spectrum disorder, such as differences in social communication and a preference for routine and predictability. These traits vary in degree across the general population.?
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A total of 505 Japanese adults aged 20 to 39 completed an online survey measuring autistic traits, discomfort with uncertainty, the tendency to put feelings into words, and anxiety levels.??
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“We measured autistic traits using a 50-item questionnaire called the Autism-Spectrum Quotient which covers five areas: social skills, the ability to shift attention, communication, imagination, and attention to detail,” said first author and doctoral student Akitaka Fujii from the at SA国际传媒.?
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The researchers found that people who scored higher on autistic traits also experience stronger anxiety in uncertain situations. This is known as intolerance of uncertainty, a tendency to react negatively when situations feel ambiguous or beyond one’s control.???

“Our findings suggest that discomfort with uncertainty is associated with a greater tendency to put feelings into words, and this is linked to lower anxiety levels,” said Masahiro Hirai, coauthor and associate professor from the Graduate School of Informatics. ?
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Offering someone the right words to describe how they feel may help them manage their anxiety. For example, a teacher or family member might say “I think you might be feeling anxious about that” when someone struggles to express distress. This perspective could inform future approaches in classroom and counseling settings.?

Limitations and next steps 

The researchers caution that these are early findings and more research is needed to confirm their theory. Because the study did not involve people with a clinical diagnosis of autism, the findings cannot be directly applied to autistic people. 
 
The Hirai Lab is currently conducting a follow-up study with adults who have a clinical diagnosis of autism to test whether similar patterns are observed. The authors highlight the need for further studies that track participants over time to determine if these patterns reflect cause and effect.  

Paper information: 

Akitaka Fujii and Masahiro Hirai, 2026. Autism related traits and anxiety in the general population are linked through intolerance of uncertainty and affect labeling. Scientific Reports, 16(13149). DOI:  

Funding information: 

This work was supported by JST SPRING (Grant Number JPMJSP2125). 

Expert contact: 

Masahiro Hirai   
Graduate School of Informatics   
SA国际传媒   
Email: hirai@i.nagoya-u.ac.jp

Media contact: 

Merle Naidoo   
International Communications Office   
SA国际传媒   
Email: icomm_research@t.mail.nagoya-u.ac.jp 

Top image:

In their paper published in Scientific Reports, Masahiro Hirai (L) and Akitaka Fujii (R) from SA国际传媒’s Graduate School of Informatics found evidence suggesting that people with higher autistic traits may try to cope with uncertainty by labeling their feelings. Credit: Merle Naidoo, SA国际传媒

Their SMART method accelerates enzyme evolution by reducing the selection period for superior variants from several weeks to a few days, and decreases overall enzyme engineering campaign costs by eliminating the need for specialized equipment.

Enzymes are proteins that catalyze chemical reactions in living organisms. They are widely applied in industries such as food production, detergents, pharmaceuticals, and chemicals. However, for commercial use, natural enzymes often need improved stability, substrate specificity, or catalytic efficiency.

Directed evolution is a Nobel Prize-winning strategy for improving proteins. It introduces artificial mutations into their genes and then selects superior variants. This approach mimics natural evolution over several weeks instead of millions of years.

A significant challenge of this approach is that artificially induced mutations can generate up to 100 trillion candidate variants, which renders the screening process extremely time-consuming and expensive.

To address this challenge, researchers at SA国际传媒 and their colleagues have developed SMART (Single-Molecule Assay on Ribonucleic acid by Translated product), an in vitro selection platform.

Their study demonstrated that SMART identifies improved enzyme variants much more rapidly and cost-effectively than conventional methods. The findings were published in the journal .

The SMART system was developed by a research group led by Associate Professor and Professor of the , in collaboration with researchers from the Institute of Science Tokyo and Saitama University. This approach successfully combines mRNA display, next-generation sequencing, and bioinformatics.

Key features of the SMART system

Typically, proteins and genes are physically separate, making it difficult and time-consuming to identify which gene encodes a discovered enzyme.

In the SMART system, puromycin acts as a chemical bridge, linking the enzyme protein to its corresponding blueprint, messenger RNA (mRNA). This mRNA display technique enables precise tracking of the relationship between individual proteins and their encoding genes at the single-molecule level.

Nakano emphasized, “In principle, there is no method for enzyme screening that is more efficient than this system. Screening enzymes at the single-molecule level has rarely been attempted before.”

SMART also incorporates an auxiliary unit for detecting enzyme activity. This study used engineered ascorbate peroxidase 2 (APEX2) as the auxiliary enzyme for oxidase screening. When the target oxidase is active and releases hydrogen peroxide (H?O?), APEX2 attaches a biotin marker to nearby molecules, enabling their isolation and capture.

Enzyme screening experiments using SMART

The researchers chose a yeast oxidase, SpDAAO, as a model enzyme because it has great potential for drug synthesis and diagnostics. The selection prioritized D-amino acids as enzyme substrates due to their growing relevance in medical applications.

The SMART method consists of several steps—creating a DNA library of enzyme variants, synthesizing enzymes in vitro, forming an mRNA display library, labeling catalytically active enzymes, isolating them with magnetic beads, and using sequencing data to guide subsequent rounds.

To assess the method, the team tested it on a simulated library with different ratios of active and inactive variants. After a single selection round, active variants were highly enriched, confirming SMART’s effectiveness.

In practical experiments, the team generated a mutant library by substituting the essential 232nd amino acid with each of the 20 other amino acids. Next-generation sequencing analysis showed that the wild-type (original form) Y232 was clearly selected (p < 0.001), reinforcing the method’s selectivity.

Initially, genetic analysis indicated selection of several variants, in addition to the original form. However, further statistical analysis identified these as experimental noise with minimal practical significance, supporting the method’s specificity.

Conclusion and future perspectives

The experiments showed that SMART selection is highly effective. At the same time, the team recognized the need for rigorous statistical analysis and careful experimentation, rather than relying solely on initial results.

The researchers expect SMART to be applicable beyond oxidases. They aim to facilitate the integration of novel enzymes into industry, establishing the system as a foundation for future enzyme development and practical biocatalytic solutions.

Publication

Kalhari Munaweera, Nana Odake, Hannah Patricia Halim, Kakeru Ikeda, Bo Zhu, Maurizio Camagna, Tomokazu Ito, Tetsuya Kitaguchi, Naoto Nemoto, Hideo Nakano, and Jasmina Damnjanovi? (2026). Harnessing the Power of SMART Single-Molecule Display for Enzyme Evolution: A Focus on Oxidase, ACS Synthetic Biology. DOI:

Funding

This work was supported by Japan Society for the Promotion of Science (JSPS) Grant-in-Aid for Early-Career scientists [grant number JP18K14387 and JP22K14828] and Grant-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) [grant number JP25H02263], the Collaborative Research Program by Network Joint Research Center for Materials and Devices (Ministry of Education, Culture, Sports, Science and Technology -Japan: MEXT), and Retention, Development, and Promotion Program Program Aiming at Maximizing the Career Potential of Female Researchers, SA国际传媒, (MEXT’s Initiative for Realizing Diversity in the Research Environment, Leadership training type for women) awarded to Jasmina Damnjanovi?, and in part by Pre-Research Unit System of the Institute of Integrated Research, Institute of Science Tokyo and JSPS Grant-in-Aid for Transformative Research Areas (A) (Publicly Offered Research) [grant number JP24H01123] awarded to Bo Zhu.

Expert contact

Jasmina Damnjanovi?
Graduate School of Bioagricultural Sciences, SA国际传媒
Email: jasmina@agr.nagoya-u.ac.jp

Media contact

Naomi Inoue
International Communications Office, SA国际传媒
Email: icomm_research@t.mail.nagoya-u.ac.jp

Top image

The SMART single-molecule display model, predicted by Alphafold3, shows SpDAAO (red) linked to a puromycin linker (magenta) through puromycin incorporation into the growing polypeptide. The mRNA (gray) is hybridized and chemically joined to the linker, connecting it to its protein, SpDAAO. An auxiliary unit is added using ORC hairpin DNA (blue) with APEX2-scCro fusion protein (green).
Credit: Hideo Nakano and Jasmina Damnjanovi?

Hiroyoshi Nishikawa

Professor of the Department of Immunology, SA国际传媒 Graduate School of Medicine, and also Chief of the Division of Cancer Immunology, Research Institute/Exploratory Oncology Research & Clinical Trial Center (EPOC), National Cancer Center

In 2022, Dr. Nishikawa was honored as one of the Highly Cited Researchers 2022 by Clarivate Analytics for a third consecutive year, following his recognition in 2020 and 2021. He continues to be a leader in the field of cancer immunology.

Don’t pretend to understand what you don’t understand.

Dr. Nishikawa said that his early work, conducted more than 20 years ago, still serves as the cornerstones of his current research.

“I was lucky to have experienced that work at the beginning. When something happens that I never expected, I can think that there’s only so much wisdom I can have, and there’s still so much I have yet to learn,” he said.

Our body’s immune system plays a crucial role in not only fighting against bacteria and viruses but also eliminating cancer. Dr. Nishikawa started his research in the field of cancer immunology in the late 1990s, when the focus was mainly on the study of killer T cells, which directly attack cancer cells.

At that time, he thought that immunity was not so simple and decided to focus his research on helper T cells, which were recognized as coordinating the immune response. However, at the time, it was believed that helper T cells only assisted killer T cells in their fight against cancer, although much remained to be understood. He divided mice with cancer into several groups and treated them in different ways:

1. Activation of killer T cells only
2. Activation of helper T cells only
3. Activation of both killer and helper T cells
4. No treatment

He expected that mice with activated killer T cells and/or helper T cells would have better prognoses although to varying degrees; but unexpectedly, mice with only activated helper T cells showed cancer progression.

Why? Though he later noticed the fact during the days of research, CD4-positive T cells, to which helper T cells belong, can actually be further classified. In reality, in addition to helper T cells supporting killer T cells in fighting cancer, another subset of CD4-positive T cells called “regulatory T cells” also exist. They play a different role by putting the brakes on killer T cells’ attacks. Immunity is such a powerful mechanism that once it gets out of control, it may cause excessive immune responses in the body. Regulatory T cells constantly monitor and control the immune system to prevent immune responses from getting out of hand.

Cancer can manipulate and exploit immune suppressive cells including regulatory T cells as a clever mechanism to evade attacks by the immune system. This mechanism may explain the results of his early research described above, in which treatment intended to activate helper T cells also activated regulatory T cells, unexpectedly leading to the protection of cancer cells. In fact, the two types of T cells work in balance with each other. CD4-positive T cells should not be lumped together as helper T cells only. The expected outcome would not be seen unless the two subsets of CD4-positive T cells are activated differently.

Dr. Shimon Sakaguchi, specially-appointed professor of the University of Osaka, discovered regulatory T cells in 1995. At the time, Dr. Nishikawa struggled with mysterious results, turned to Dr. Sakaguchi’s research on regulatory T cells, thinking that it could be the key. Thus, he found the key to the solution and eventually paved the way for cancer immunology research.

He said, “Actually, immunology was my least favorite subject as a medical student. The theory at that time seemed like a patchwork of disconnected information that was being forced together. I couldn’t understand it very well.”

There are significant factors, such as one’s position as a researcher and research trends at the time, that determine one’s research theme. At the time, it must have taken courage for Dr. Nishikawa to focus on studying helper T cells.

“It is important for researchers to sincerely face the occurring phenomena. We should not pretend to understand what we don’t understand,” he said.

When you cannot explain well a phenomenon you are seeing or when you do not feel fully convinced, there is surely something wrong. An attitude of not running away from such dissatisfaction can lead to new findings.

A saying of his boss serves as his driving force: “If you see one phenomenon, continue to sit in front of it until you have written five papers on it.”

The research of Dr. Tasuku Honjo, who is the Nobel Prize laureate in Physiology or Medicine 2018, has opened up a new field of cancer treatment known as “cancer immunotherapy,”  particularly, “PD-1 blockade therapy”. One drug used in this therapy is nivolumab (Opdivo).

Killer T cells typically do not attack unless they can recognize and identify other cells as their attack targets. This is another mechanism that prevents excessive immune response, and cancer cells can also take advantage of this mechanism to suppress the attackers. Cancer cells provide a “certificate” that they are not the attack targets as another means of escape. Killer T cells are slowed down and cannot show their ability to attack in the presence of this certificate. PD-1 blockade therapy including Opdivo has the function of nullifying this certificate, allowing killer T cells to attack cancer cells.

Cancer immunotherapy is a relatively new field of medicine. Unfortunately, PD-1 blockade therapy is only effective in 20% to 30% of eligible cancer cases, for some reasons not entirely explained. Dr. Nishikawa has proven one of the reasons.

“The immune system works properly in a positive and negative balance. I realized the phenomenon I encountered 20 years ago commonly underlied the results of my current work,” he said.

It has been shown that PD-1 blockade therapy activates not only killer T cells but also regulatory T cells surrounding cancer. Therefore, the key to the efficacy of the drug is the balance between the two types of T cells. If regulatory T cells in the periphery of cancer are strong, the killer T cells will eventually be outcompeted by them.

Dr. Nishikawa’s research progressed further, and the next step was to demonstrate exactly what determines the balance between killer and regulatory T cells. He turned his attention to cancer metastases in the liver, which are particularly resistant to PD-1 blockade therapy.

The liver is a metabolically active organ that receives abundant nutrients supplied from the digestive system such as the large and small intestines. The liver consumes a large amount of glucose to generate energy for metabolism, which results in the release of lactic acid. Cancer cells also consume high amounts of glucose to grow and divide. Metastatic cancer tissues in the liver are richer in lactic acid than other tissues.

“What I keep in my mind during my research on cancer immunology is to have both the viewpoints of cancer and immunity. I’ve noticed that regulatory T cells can utilize lactic acid, which hasn’t received attention in previous studies,” said Dr. Nishikawa.

Killer T cells and most other types of immune cells use glucose as an energy source for their activities, but they cannot use lactic acid. In an area where a large number of immune cells are accumulating and actively working, glucose levels decrease while lactic acid levels increase. In such an environment, regulatory T cells, which can utilize lactic acid, would not have any trouble obtaining an energy source, allowing them to constantly monitor and control immune responses.

Furthermore, Dr. Nishikawa has demonstrated that high levels of lactic acid slow down the activity of killer T cells; this suggests that metastatic cancer in the liver may be a more favorable environment for regulatory T cells than for other immune cells.

This series of discoveries has provided new insights into the study of cancer immunology, and has significantly impacted clinical practice. It is a great advance to identify patients who are not expected to respond to PD-1 blockade therapy, considering their cost and potential side effects.

Dr. Nishikawa has accomplished many studies, and describes himself as “being persistent” when it comes to his research, while attributing much of his success to advances in science and technology and to superior researchers who have supported him. His research attitude can be traced back to the time when he was a researcher at the Memorial Sloan-Kettering Cancer Center in New York, U.S., from 2003 to 2006. His boss at the time, Dr. Lloyd J. Old, was a renowned leader in the field of cancer immunology.

“He told me that when you see one phenomenon, continue to sit in front of it until you have written five papers on it. It’s pretty hard to write five papers, but I learned from him the attitude of doing as much as I can to solve a series of things,” said Dr. Nishikawa.

The immune system is purposeful, interesting, and beautiful.

When and how does the immune system find and recognize cancer cells? Does the judgment of whether or not something is foreign depending on the situation? Can we create killer T cells that can utilize lactic acid?

Questions arise in his mind one after another. The immune system is very complex, and much of it is still a mystery. Therefore, efforts may not yield fruitful results. “It’s daunting, and there’s so much I don’t understand yet, but that’s what makes it exciting,” Dr. Nishikawa stated. Each of his words sounds as if it conveys a spark of curiosity.

“While study immunology, I sometimes feel thrilled at such a complex but sophisticated mechanism present in our bodies, and the more I study, the more I am amazed and can only stand in awe of it. When I think something is wrong and research it again, I get exactly the results I was looking for. The immune system is so amazing that it makes me realize that human understanding is so far behind,” he said.