Members

Katsuhito Fujiu

Professor, Institute of Integrated Research, Institute of Science Tokyo

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Chronic stress arising from conditions such as heart failure is not confined to the affected organ. It is inscribed in hematopoietic stem cells (HSCs) as epigenetic change, a form of innate immune memory that predisposes the individual to subsequent multimorbidity and disease recurrence. This project aims to establish a diagnostic method that reads this stress memory and predicts multimorbidity risk before disease onset. Using animal models of heart failure, aging and metabolic stress, together with single-cell transcriptomic and chromatin accessibility analyses, we are defining how stress memory is written into HSCs. In parallel, we are developing an approach that captures the state of HSCs and monocytes from a small volume of human peripheral blood and interprets it using AI. We are also advancing non-contact sensing of physiological information, such as camera-based measurement of vital signs, so that data acquired unobtrusively in daily life can be integrated with these blood-derived indices. Together, these technologies are intended to stratify risk before symptoms appear and to enable genuinely pre-symptomatic prevention.

Tetsuya Yamada

Professor, Graduate School of Medical and Dental Sciences, Institute of Science Tokyo

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We are developing an AI-powered method to detect very early signs of diabetes using contact devices without the need for blood tests. Furthermore, we are collaborating with industry to advance research so that this developed technology can enable early detection of diabetes, leading to a society where the onset of diabetes can be prevented through lifestyle interventions.

Gen Tamiya

Professor, Tohoku University Graduate School of Medicine

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By integrating family history, epidemiological data, and clinical information into the Palette PRS, which is categorized by clinical subtypes based on gene pathways and inter-organ network information -we aim to develop and refine a precise risk assessment model for the pre-diabetic and ultra-early stages of diabetes. Furthermore, we will extend this approach to the prediction of complications and validate it through a combination of retrospective studies using existing data and prospective studies in clinical settings. Through this, we will clarify the practical applicability and challenges of the method, feed our findings back into basic research, and promote collaborative clinical and basic research that integrates pathophysiological elucidation with model refinement.

Katsuhito Fujiu

Professor, Institute of Integrated Research, Science Tokyo

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Chronic stress arising from conditions such as heart failure is not confined to the affected organ. It is inscribed in hematopoietic stem cells (HSCs) as epigenetic change, a form of innate immune memory that predisposes the individual to subsequent multimorbidity and disease recurrence. This project aims to establish a diagnostic method that reads this stress memory and predicts multimorbidity risk before disease onset. Using animal models of heart failure, aging and metabolic stress, together with single-cell transcriptomic and chromatin accessibility analyses, we are defining how stress memory is written into HSCs. In parallel, we are developing an approach that captures the state of HSCs and monocytes from a small volume of human peripheral blood and interprets it using AI. We are also advancing non-contact sensing of physiological information, such as camera-based measurement of vital signs, so that data acquired unobtrusively in daily life can be integrated with these blood-derived indices. Together, these technologies are intended to stratify risk before symptoms appear and to enable genuinely pre-symptomatic prevention.

Junken Aoki

Professor, Graduate School of Pharmaceutical Sciences, The University of Tokyo

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Our research project is a unique initiative, both domestically and internationally, that centers on lipidomics analysis focusing on plasma phospholipids to identify biomarkers indicating ultra-early-stage risk for diabetes and its comorbidities, and comprehensively investigates the molecular mechanisms—including those mediated by responsible enzymes and GPCRs—as well as interventions using phospholipid supplements. We will proceed with the identification of lipid species correlated with blood glucose levels, HbA1c, insulin resistance indices, and lifestyle data, and elucidate their functions.

Hideki Katagiri

Professor, Tohoku University Graduate School of Medicine

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Longitudinal data from a human cohort revealed various candidate blood markers correlated with diabetes development. Taking advantage of multi-omics analysis, we will identify the potentially useful markers and their optimal combinations, and proceed with their validation.

Asuka Inoue

Professor, Graduate School of Pharmaceutical Sciences, Kyoto University

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We use GPCR signaling assays to identify the receptors targeted by metabolite markers of diabetes and its associated diseases. Building on this, we develop highly sensitive assays that measure these metabolites in clinical samples. We also apply chemogenetic tools that activate defined GPCR signals on demand, letting us test how each signal contributes to disease and whether its manipulation is therapeutically useful. Our goal is to make diabetes and its related conditions easier to predict and prevent.

Takayuki Doi

Professor, Graduate School of Pharmaceutical Sciences, Tohoku University

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We synthesize labeled probes for visualizing phospholipids to discover biomarkers for early disease diagnosis and prevention.

Makoto Kurano

Professor, The University of Tokyo

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By conducting comprehensive analyses of clinical data and lipidomics analysis with a primary focus on phospholipids of clinical samples, we aim to develop innovative clinical diagnostic tests capable of predicting both the initial onset of diabetes and the subsequent progression of its related complications. Through these scientific endeavors, we aim to make substantial contributions to the advancement of preemptive healthcare as well as the broader field of preventive medicine.

Furthermore, we seek to deeply explore and elucidate the complex molecular foundations underlying diabetes, which will help us to develop novel preemptive and preventive therapeutic strategies.

Kazuhiro Nakamura

Professor, Nagoya University Graduate School of Medicine

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We investigate the bidirectional interplay between the central and peripheral nervous systems and the mechanisms by which this interplay coordinates inter-organ networks. Our goal is to identify the neural circuits that govern physiological homeostasis and reveal the principles underlying their function. We further examine how aging and nutritional environments alter these circuits and thereby develop conditions such as obesity, leptin resistance, and diabetes. Ultimately, our study will provide a foundation for developing new therapeutic drugs and technologies to prevent and treat these disorders.

Yukio Nishimura

Project Leader, Tokyo Metropolitan Institute of Medical Science

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Using non-invasive magnetic stimulation, we aim to determine whether targeting spinal autonomic circuits that control the pancreas can modulate blood glucose and other metabolic measures. We will assess the feasibility of this approach as a low-burden method for regulating glucose metabolism, with potential application to individuals at the pre-disease stage.

Misa Yoshimoto

Professor, Faculty of Human Life and Environments, Nara Women's University

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The autonomic nervous system plays a critical role in maintaining energy metabolic homeostasis through bidirectional communication between the brain and individual organs, yet how this communication dynamically changes and what roles it plays remain largely unclear. Using animal models, we continuously and simultaneously measure vagal nerve activity, sympathetic nerve activity, energy metabolism, and hemodynamics, aiming to elucidate the dynamic coupling among these parameters—an aspect that conventional, fragmentary measurements could not capture. In particular, we are developing a technique for long-term continuous recording of vagal nerve activity, with the goal of decoding the physiological meaning of this bidirectional brain–organ signaling.

Hideki Katagiri

Professor, Tohoku University Graduate School of Medicine

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Since the liver is an organ that directly receives food-derived nutrients via the portal vein, its metabolism has a great impact on systemic glucose metabolism and also serves to transmit nutritional information. Furthermore, the liver is an organ capable of producing and releasing glucose. Therefore, by regulating these unique properties of the liver, we aim to explore strategies that lead to the prevention of diabetes, sarcopenia and obesity.

Kazuhiro Suzuki

Professor, Graduate School of Medicine, The University of Osaka

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Chronic inflammation in adipose tissue associated with obesity has been recognized as a key driver of diabetes, highlighting the inflammatory nature of this disease. This project aims to elucidate the role of plasma cells, the terminally differentiated form of B lymphocytes, in obesity and to pave the way for the development of ultra-early diagnostic and preventive strategies for obesity-related diseases, including diabetes.

Yutaka Hasegawa

Associate Professor, Department of Internal Medicine, Iwate Medical University

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We aim to elucidate the mechanisms underlying the prevention and onset of diabetes and to translate this understanding into systemic metabolic regulation and therapeutic strategies. By performing blood metabolome profiling and volatile organic compound analysis before and after bariatric/metabolic surgery in patients with severe obesity, we identify metabolites that contribute to the prevention, onset, and progression of diabetes and obesity, and clarify their biological functions and roles. In addition, candidate proteins involved in the prevention and treatment of obesity and diabetes are extracted from human adipose tissue, and their physiological and pathological significance is analyzed. Furthermore, our screening of thousands of compounds targeting thermogenic uncoupling protein 1 (UCP1) activity in brown adipocytes has led to the identification of several lead compounds capable of enhancing basal metabolism and potentially suppressing obesity and improving diabetes. This research project aims to elucidate their mechanisms of action and to advance drug development through systemic optimization.

Toshiaki Teratani

Specially Appointed Associate Professor, Keio University School of Medicine

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Our research aims to elucidate the gut microbiota–gut–brain network through which microbial and neural signals regulate feeding behavior, intestinal immunity, and systemic metabolism. We investigate how metabolites produced by specific gut microbes are sensed by enteroendocrine cells and transmitted through vagal sensory pathways to shape nutrient preference and metabolic functions. In parallel, we investigate how selective stimulation of the hepatic branch of the vagus nerve regulates intestinal immune homeostasis. Through these studies, we aim to understand how the gut microbiota and vagal neural circuits coordinately regulate behavior, immunity, and metabolism, and ultimately develop novel strategies to improve eating behavior and metabolic diseases by restoring a healthy gut environment.

Ichiro Manabe

Professor, Graduate School of Medicine, Chiba University

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We investigate how diverse stresses, including heart failure, imprint lasting memories on the hematopoietic and innate immune systems to drive disease progression and the development of multimorbidity, with the goal of establishing early risk diagnosis and novel preventive and therapeutic strategies.

Shinji Kume

Professor, Department of Medicine, Shiga University of Medical Science

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My research aims to elucidate the molecular and metabolic mechanisms that enable organisms to maintain systemic homeostasis during fasting and other nutritional challenges. By integrating metabolomics, epigenomics, stable isotope–based metabolic flux analysis, and multi-organ approaches, I investigate how adaptive metabolic responses coordinate inter-organ communication to preserve energy balance under nutrient-deprived conditions. A particular focus of my work is the role of ketone body metabolism, not only as an alternative energy source but also as a signaling and epigenetic regulator that modulates cellular function and tissue adaptation. I aim to clarify how ketone body production and utilization contribute to metabolic flexibility and organ-specific responses, and how disruption of these adaptive mechanisms impairs tissue homeostasis. Ultimately, my research aims to define the molecular basis by which failure of fasting-induced metabolic adaptation drives the development and progression of diabetic complications, comorbidities, and other metabolic disorders, thereby providing a foundation for novel therapeutic strategies.

Kuniyasu Niizuma

Professor, Graduate School of Biomedical Engineering, Tohoku University

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We focus on stroke as a major complication of diabetes and regard diabetes as an important pre-disease stage in the development of stroke. Our research aims to establish novel strategies both to prevent stroke in patients with diabetes and to treat diabetes-associated stroke, which is often linked to an increased risk of severe outcomes. In particular, we focus on transfer RNA (tRNA), including its modification and metabolism, as a previously underexplored regulatory layer in the pathophysiology of diabetes and stroke. By elucidating how alterations in tRNA-related pathways contribute to the transition from diabetes to stroke onset and subsequent brain injury, we aim to uncover novel disease mechanisms that cannot be fully explained by conventional approaches. Ultimately, we seek to translate these findings into new preventive and therapeutic strategies for stroke associated with diabetes.

Kazuto Masamoto

Professor, Graduate School of Informatics and Engineering, University of Electro-Communications

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We aim to establish a multimodal analytical platform to capture the disruption of microvascular endothelium integrity homeostasis in the early stages of diabetes. Our primary goal is to quantitatively define the initial processes by which humoral factors such as endothelin, triggered by hypoxia and inflammation, induce downstream microvessel contraction and glycocalyx shedding. Furthermore, we are advancing non-invasive microcirculation monitoring by integrating AI-based automated analysis into nailfold video capillaroscopy (NVC). By extracting precise features of capillary functions and blood flow fluctuations from large-scale datasets, we aim to develop an early screening technology for the prediction and personalized prevention of vascular complications.

Hideki Katagiri

Professor, Tohoku University Graduate School of Medicine

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We obtained results from animal experiments showing that stimulating the vagal nerve innervating the pancreas can increase pancreatic beta cells. Therefore, to determine whether mechanical vagal nerve stimulation increases pancreatic beta cells in humans and, furthermore, whether it can prevent or treat diabetes, we will proceed with clinical trials using vagal nerve stimulation devices.

Kuniyasu Niizuma

Professor, Graduate School of Biomedical Engineering, Tohoku University

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This study aims to translate preclinical findings showing that vagus nerve stimulation (VNS) can increase pancreatic β-cell mass and improve glucose metabolism into a clinical setting. Patients who are scheduled to undergo VNS device implantation will be prospectively evaluated beginning before implantation. Diabetes-related parameters, including glucose control and insulin secretion, will be measured at baseline and longitudinally after VNS initiation, allowing within-patient assessment of physiological changes induced by stimulation. Through this approach, we aim to determine whether VNS influences pancreatic β-cell function and systemic glucose metabolism in humans. By bridging preclinical evidence with longitudinal human data, this study seeks to clarify neural regulation of pancreatic function and explore the potential of neuromodulation as a novel strategy for the prevention or treatment of diabetes.

Hideki Katagiri

Professor, Tohoku University Graduate School of Medicine

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We will elucidate the full picture—including the molecular mechanisms—of the inter-organ communication that promotes to increase pancreatic β-cells. We aim to identify chemical compounds that can prevent/treat diabetes through the increase in pancreatic β-cells by stimulating this interorgan network. In this project, we aim to obtain findings which will provide the basis for clinical trials.

Tetsuya Yamada

Professor, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University

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We are developing strategies to prevent diabetes by promoting energy metabolism at the individual level. Specifically, we aim to elucidate the molecular mechanisms of energy metabolism in the inter-organ network consisting of "liver - vagus nerve - brain - sympathetic nerve - peripheral tissues and cells (brown adipose tissue (BAT), beige adipocytes, adrenal glands, etc.)" and each tissue that constitutes the network, thereby proposing strategies that contribute to the prevention of diabetes by promoting energy metabolism at the individual level.

Ikuo Kimura

Professor, Graduate School of Biostudies, Kyoto University

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This project aims to elucidate the mechanisms by which dietary and gut microbiota-derived lipid metabolites regulate host homeostasis through membrane receptors. We particularly focus on understanding the multi-organ energy metabolism network originating from the intestine and its regulation by diet and the intestinal environment. By identifying novel metabolites and receptor-mediated signals that enhance physiological resilience and homeostasis, we seek to establish new strategies for preventing diabetes and related metabolic disorders and ultimately translate these findings into the development of functional supplements and therapeutic agents.

Ikuo Kimura

Professor, Graduate School of Biostudies, Kyoto University

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This project aims to elucidate how gut microbiota metabolize dietary carbohydrates and how the resulting metabolites influence host health, with the goal of developing beneficial microorganisms and their metabolites as functional food ingredients for diabetes prevention. Using probiotic candidate strains identified through this project, we will develop a multi-biotic formulation and conduct preclinical studies and formulation development for human use. Its efficacy and safety will subsequently be evaluated in clinical trials to validate in humans the beneficial effects demonstrated in animal models. Ultimately, we aim to establish the evidence required for commercialization as a functional food and dietary supplement for the prevention of diabetes.

Hiroshi Suito

Professor, Advanced Institute for Materials Research, Tohoku University

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Our research group is responsible for mathematical modeling of the circulatory system—a critical pathway in inter-organ networks—and its application to analyzing diabetic comorbidities. Because the circulatory system operates across multiple scales, capturing its fluid dynamics requires an integrated representation of the entire network. To achieve this, we build and implement mathematical models that combine systems of partial differential equations (PDEs), ordinary differential equations (ODEs), parameter identification procedures, and techniques for balancing these complex systems.

Masaharu Nagayama

Professor, Research Institute for Electronic Science, Hokkaido University

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This research project aims to integrate a whole-body circulatory network model based on glucose and insulin dynamics with machine learning to elucidate and predict ultra-early pathological states during the transition from health to the onset of diabetes. By advancing the mathematical model, we seek to clarify the mechanisms underlying the development of diabetes and identify indicators that capture ultra-early disease stages. Furthermore, we will develop a machine-learning model incorporating features derived from the mathematical model, enabling estimation of the probability of diabetes onset and classification of ultra-early disease stages from individual OGTT data, ultimately leading to a personalized prediction system.

Keita Iida

Associate Professor, Institute for Protein Research, Osaka University

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Within cells, many molecules interact with one another and continuously change their states in response to external signals. In this study, we reconstruct intracellular signalling dynamics as mathematical models from omics data and use mathematics to uncover the principles that govern these dynamics. We then aim to infer metabolic states at the organ and whole-body levels from cellular responses. By connecting these approaches, we seek to build a new research framework that integrates mathematics and medicine, with the ultimate goal of contributing to the prediction and control of diabetes and its comorbidities.

Jun Takayama

Associate Professor, Tohoku University Graduate School of Medicine

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Our organs do not work in isolation. The liver, fat tissue, and pancreas constantly exchange signals with the brain through nerves, and this inter-organ network keeps blood glucose stable. Diabetes is thought to begin when the network starts to drift, long before anything abnormal appears in a blood test. My role is to make sense of the data that captures these early changes. Together with the experimental groups in the project, I analyze single-cell RNA sequencing data, which measures gene activity in individual cells, from tissues including the pancreas, adipose tissue, and the vagal ganglia that relay signals from the liver to the brain. Pinpointing which nerve cell types respond to a liver signal is hard: the cells are rare and published classifications disagree. We therefore adapted an AI foundation model trained on tens of millions of cells, which lets us resolve far finer subtypes than before. I also maintain the shared data infrastructure of the project and hand the results to our mathematical modeling colleagues, so that biology and mathematics work together toward a future in which diabetes is found before it develops.

Masaki Nagao

Assistant Professor, Graduate School of Medicine, The University of Tokyo

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Constructing a developmental atlas of fetal mice under normal and gestational diabetic conditions. Establishing an AAV-based mouse model of central nervous system insulin resistance to investigate sleep–wake regulation and neurovascular alterations.

Hiroshi Kobayashi

Associate Professor, Tohoku University Graduate School of Medicine

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Diabetes develops through gradual changes across multiple organs and cell types long before clinical symptoms appear. In this project, we will use AI foundation models to analyze and integrate single-cell gene expression data from tissues throughout the body in humans and experimental models. By integrating representations of individual tissues, we aim to model how coordinated whole-body systems progressively lose their balance and transition toward diabetes in a high-dimensional space. We will further combine these models with diverse biological and clinical data collected from cohort studies. Through this integrated approach, we seek to characterize the pre-disease state of diabetes, predict future disease risk, and identify new targets for prevention and early intervention.