Speaker: Seitaro Nomura（Project Associate Professor, Graduate School of Medicine, The University of Tokyo）

Title: coming soon

Date&Time: 27 May (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=136783

Abstract:

coming soon

Speaker: Takeshi Yagi（Guest professor, Graduate School of Frontier Biosciences, Osaka University）

Title: Exploring the role of neuronal individuality in neuronal survival and brain function

Date&Time: 13 May (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=136783

Abstract:

In the brain, individual neurons form precise and complex neural networks that underlie a wide range of brain functions, including cognition, emotion, motor control, and the formation of massive memories. Recent studies have revealed that each neuron possesses distinct molecular, structural, and functional identities. However, the fundamental question of how such individuality arises and how it contributes to the organization of brain functions and behavioral control remains unresolved. Our previous work identified the clustered protocadherin (cPcdh) gene family as key molecules that generate neuronal individuality by producing random yet combinatorial gene expression patterns (Morishita & Yagi, Curr Opin Cell Biol, 2007). These molecules have been implicated in neuronal survival, dendritic and axonal self-recognition, circuit formation, and behavioral regulation. Despite these insights, the functional significance of the stochastic expression of cPcdh genes remains incompletely understood. Here we aim to elucidate the molecular mechanisms by which randomly expressed cPcdh genes regulate neuronal survival and synapse formation. Furthermore, by capturing and manipulating the stochastic expression of cPcdh, we investigate how neuronal individuality contributes to the establishment of complex and precise neural networks and the formation of higher-order brain functions.

Speaker: Naoki Ito（Brain-Skeletal Muscle Connection in Aging Project Team, National Center for Geriatrics and Gerontology）

Title: Novel molecular pathogenesis of sarcopenia induced by impaired liver-skeletal muscle crosstalk during aging

Date&Time: 25 February (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract:

Sarcopenia is a progressive disease characterized by an age-related decline in skeletal muscle function. The fundamental molecular pathogenesis of sarcopenia remains unclear. Our research focuses on the age-related impairment of nicotinamide adenine dinucleotide (NAD+) metabolism and inter-organ communication in sarcopenia during aging1,2. In this study, I will discuss about the novel molecular pathogenesis of sarcopenia, lactic acidosis in skeletal muscle, which is caused by impaired liver-skeletal muscle crosstalk. Systemic lactate tolerance was decreased in aged mice due to the impaired liver lactate processing capacity, which caused the accumulation of lactate and intracellular acidification, lactic acidosis, in skeletal muscle. This lactic acidosis in skeletal muscle leads to decreased NAD+ levels and subsequent skeletal muscle dysfunction. Crucially, the pharmacological activation of hypoxia-inducible factor (HIF) or the liver-specific activation of HIF1α improved age-related impairment in lactate tolerance, lactic acidosis in skeletal muscle, and sarcopenia. Our results demonstrate that lactic acidosis in skeletal muscle is a novel molecular cause of sarcopenia and highlight HIF1α in the liver as a pharmacological target for treating sarcopenia.

Reference:

Naoki Ito, Ai Takatsu, Hiromi Ito, Yuka Koike, Kiyoshi Yoshioka, Yasutomi Kamei, Shin-ichiro Imai. Slc12a8 in the lateral hypothalamus maintains energy metabolisms and skeletal muscle functions during aging. Cell Reports. 40(4). 111131. 2022.

Speaker: Yasutaka Motomura（Assistant Professor, Faculty of Science and Technology, Tokyo University of Science）

Title: Early-Life Immune Programming Shapes Allergic Susceptibility

Date&Time: 18 February (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract:

Immunoglobulin E (IgE) is thought to have evolved as a host defense mechanism against parasitic infections, mediating rapid immune responses and parasite expulsion via activation of mast cells and basophils. While beneficial under strict regulatory control, IgE responses can become pathogenic when this balance is disrupted by environmental changes, including dietary factors, leading to allergic disease. Thus, IgE lies at a critical immunological junction between parasite defense and allergy, and understanding its dysregulation is essential to elucidate allergic disease pathogenesis.

Epidemiological studies indicate that early-life events such as infantile dermatitis, antibiotic exposure, and dietary factors are associated with sustained IgE elevation and an increased lifetime risk of allergic disease. These findings suggest that environmental influences during infancy disrupt IgE regulation and promote long-term allergic predisposition. To investigate this, we established a mouse model of environmentally induced IgE production. Consistent with human observations, infantile dermatitis induced long-lasting IgE enhancement, which exacerbated allergic pathology in adulthood, demonstrating that early-life dysregulation of IgE control increases lifelong allergic susceptibility. Moreover, we identified a contribution of innate immune mechanisms to early-life IgE induction, revealing a previously unrecognized innate immune–driven IgE pathway. Elucidation of this mechanism may enable precise control of IgE responses for both allergy prevention and parasite defense.

Reference:

1. Otaki, N., Motomura, Y., Terooatea, T., Thomas Kelly, S., Mochizuki, M., Takeno, N., Koyasu, S., Tamamitsu, M., Sugihara, F., Kikuta, J., Kitamura, H., Shiraishi, Y., Miyanohara, J., Nagano, Y., Saita, Y., Ogura, T., Asano, K., Minoda, A., Moro, K. Activation of ILC2s through constitutive IFNγ signaling reduction leads to spontaneous pulmonary fibrosis. Commun. 14, 8120, (2023)
2. Hikichi, Y., Motomura, Y*., Takeuchi, O., Moro, K*. Posttranscriptional regulation of ILC2 homeostatic function via tristetraprolin. J Exp Med 218, (2021) *Co-coresponding

Speaker: Hiroshi Makino (Professor, Department of Physiology, Keio University School of Medicine）

Title: Learning in intelligent systems

Date&Time:  28 January(wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract: 

Recent years have seen a resurgence of interplay between artificial intelligence (AI) and neuroscience. While AI offers new theories on how the brain solves complex problems, neuroscience contributes novel algorithms and neural network architectures that can endow machines with cognitive abilities. However, direct comparisons between artificial and biological intelligent systems remain limited. We addressed this gap by examining behaviors and neural representations across multiple domains of intelligence. By training mice and deep reinforcement learning (RL) agents on the same tasks and analyzing the resulting task representations in their respective neural networks, we found that learning in the mouse cortex exhibits key features reminiscent of deep RL algorithms. Furthermore, by deriving theoretical predictions from AI models and empirically testing them in mice, we discovered that the brain composes novel behaviors through a simple arithmetic combination of pre-acquired action-value representations and a stochastic policy. These findings underscore the remarkable parallels in behaviors and neural representations between the two systems and highlight the value of comparative approaches.

References:

1. Makino, H.*, and Suhaimi, A. 2025. Distributed representations of temporally accumulated reward prediction errors in the mouse cortex. Sci Adv 11, eadi4782.
2. Makino, H.* Arithmetic value representation for hierarchical behavior composition. Nat Neurosci 26, 140-149.
3. Suhaimi, A., Lim, A.W.H., Chia, X.W., Li, C., and Makino, H.* Representation learning in the artificial and biological neural networks underlying sensorimotor integration. Sci Adv 8, eabn0984.

Speaker: Kai Otsuka (Assistant Professor,  Faculty of Science and Technology, Tokyo University of Science）

Title: Potential function of KRAB zinc-finger proteins in murine spermatogenesis.

Date&Time:  17 December (wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract: 

More than half of the mammalian genome consists of transposable elements (TEs) which originated from retroviral invasions into ancestral genomes during evolution. TEs pose a potential risk for the host genome, as their transposition can disrupt endogenous genes and regulatory elements. To counteract this threat, host cells -especially germ cells, only the cell type that transmits its genome to the next generation- have developed a multi-layer defensive system against retroviruses, including piRNAs, DNA methylation, and other epigenetic machinery, to safeguard genome integrity.

Recently, we discovered that KRAB zinc-finger proteins (KZFPs), the most rapidly evolving transcription factors, bind to young TEs and serve repressive epigenetic marks, H3K9me3, in spermatogonia, suggesting an additional layer of genome protection against TEs. We also found an evolutionary relationship between KZFPs and their target TEs, implying that a co-opting arms race takes place in germlines in mammalian evolution. To elucidate the biological roles of KZFPs in male germline development, we newly generated mutant mice, which carry multiple KZFPs-cluster-deletions.

Our morphological analyses revealed a significant reduction of germ cells in the neonatal mutant testis at postnatal day (PD) 3. Notably, while nearly half of the tubules lacked germ cells, the remaining half retained normal germ cells, resulting in two distinct tubule populations. Interestingly, spermatogenesis appeared to progress normally, although was only observed in approximately half of the tubules as well. Additionally, a small but certain number of sperm were observed in the adult mutant cauda epididymis.

These observations led us to hypothesize that the role of KZFPs may not be involved in stem-cell maintenance, the progression of meiosis, or post-meiotic events but rather play a role in an earlier stage, such as embryonic germ cells. Here, we present the recent data in the mutant mice and discuss the biological significance of KZFPs in male germ cell development.

Speaker: Yusuke Nasu (Assistant Research Fellow, Institute of Biological Chemistry, Academia Sinica）

Title: Shedding light on in vivo metabolism: genetically encoded fluorescent biosensors for L-lactate

Date&Time:  10 December (wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract: 

Traditionally regarded as a metabolic waste product of glycolysis, L-lactate (lactic acid) is now recognized as a key metabolite that functions both as an energy substrate and a signaling molecule. One prominent and debated model, the astrocyte-to-neuron lactate shuttle (ANLS) hypothesis, proposes that astrocyte-derived L-lactate is exported into the extracellular space and subsequently imported into neurons, where it is metabolized to support adenosine triphosphate (ATP) production during periods of elevated neuronal activity.
While genetically encoded calcium biosensors (e.g. GCaMP) have revolutionized our ability to monitor neuronal activity in vivo, tools for real-time imaging of key metabolites like L-lactate have lagged behind, limiting our ability to simultaneously interrogate neuronal activity and metabolism. This technical gap has hindered direct experimental validation of hypotheses such as ANLS.
In this seminar, we showcase the LACCO biosensor series, a family of genetically encoded fluorescent L-lactate biosensors engineered through directed protein evolution. These biosensors exhibit high sensitivity, specificity, and brightness, enabling dynamic visualization of L-lactate with subcellular resolution in living cells and in vivo. Using the LACCO biosensors and GCaMP biosensor, we demonstrated the concurrent imaging of neuronal activity and metabolism in awake mice. These results provide new avenues for dissecting metabolic coupling in the brain and represent a major technological advancement toward resolving long-standing debates such as the ANLS hypothesis.

References

1. Nasu Y., Shen Y., et al. “Structure- and mechanism-guided design of single fluorescent protein-based biosensors”, Nature Chemical Biology, 17, 509−518 (2021) https://doi.org/10.1038/s41589-020-00718-x
2. Nasu Y., et al. “A genetically encoded fluorescent biosensor for extracellular L-lactate”, Nature Communications, 12, 7058 (2021) https://doi.org/10.1038/s41467-021-27332-2
3. Nasu Y. et al. “Lactate biosensors for spectrally and spatially multiplexed fluorescence imaging”, Nature Communications, 14, 6598 (2023) https://doi.org/10.1038/s41467-023-42230-5
4. Kamijo Y., et al. “A red fluorescent genetically encoded biosensor for in vivo imaging of extracellular L-lactate dynamics”, Nature Communications, 16, 9531 (2025) https://doi.org/10.1038/s41467-025-64484-x

Speaker: Yoichi Wada (Lecturer, SiRIUS Institute of Medical Research, Department of Medical Science and InnovationTohoku University)

Title: Galactose Mutarotase Deficiency as the type IV Galactosemia

Date&Time:  26 November (wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract: 

Galactosemia comprises a group of inherited enzyme defects in the Leloir pathway, which metabolizes dietary galactose generated by lactose hydrolysis. Disruption of the Leloir pathway leads to accumulation of galactose and its metabolites. Historically, three enzymatic forms were recognized. In 2019, we identified a fourth form — galactose mutarotase (GALM) deficiency (MIM #618881). GALM (aldose‑1‑epimerase, EC:5.1.3.3) catalyzes the interconversion of α‑ and β‑D‑galactose at the entry point of the Leloir pathway; loss of GALM activity results in accumulation of galactose and its polyol, galactitol, generated from the open‑chain aldehyde. Excess galactitol appears to promote osmotic cataract formation, paralleling other galactosemias. To date, aside from cataracts and transient transaminitis, no additional complications have been consistently documented in GALM deficiency. However, the condition should not be regarded as benign, given clinical experience with irreversible cataracts. A nationwide survey estimated a prevalence of 1 in 181,835, while a separate population‑based estimate 1 in 80,747 derived from genome database analyses and in vitro functional evaluation. Dietary lactose restriction remains the cornerstone of management for galactosemias, including GALM deficiency. Additionally, we have demonstrated that β‑galactosidase supplementation can attenuate elevations in blood galactose in GALM deficiency, supporting its candidacy as an adjunct therapy. This seminar will trace the discovery of GALM deficiency and summarize current understanding, including results of recent research.

References:

Wada, Y. et al. Biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet Med 21, 1286–1294 (2019).

Iwasawa, S. et al. The prevalence of GALM mutations that cause galactosemia: A database of functionally evaluated variants. Mol Genet Metab 126, 362–367 (2019).

Wada, Y. et al. β-Galactosidase therapy can mitigate blood galactose elevation after an oral lactose load in galactose mutarotase deficiency. J Inherit Metab Dis 45, 334–339 (2022).

Mikami-Saito, Y. et al. Phenotypic and genetic spectra of galactose mutarotase deficiency: A nationwide survey conducted in Japan. Genet Med. 26, 101165 (2024).

Speaker: Akira Kurisaki (Professor, Stem Cell Technologies Lab, Division of Biological Science, Nara Institute of Science and Technology)

Title:  Mechanisms of gastric tissue differentiation and the control of homeostasis

Date&Time:  5 November (wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract: 

The adult stomach performs digestive functions through various
specialized cell types, including parietal cells that secrete gastric
acid, chief cells that produce digestive enzymes, and pit cells that
secrete large amounts of mucus to protect the luminal surface of the
stomach lining. We established a differentiation culture system that
enables the generation of gastric mini-tissues from pluripotent stem
cells, providing an in vitro model to investigate the mechanisms
underlying gastric differentiation.

Furthermore, focusing on stem cells in the adult stomach, we explored
candidate signaling pathways regulating the differentiation of adult
gastric epithelial stem cells by performing pseudotime-dependent gene
enrichment analysis of single-cell RNA sequencing data from adult
gastric tissue. Using these candidate factors, we conducted
differentiation assays on gastric epithelial stem cells isolated and
expanded from adult gastric tissue. Our results revealed that EGFR–ERK
signaling promotes differentiation into pit cells, whereas NF-κB
signaling maintains gastric progenitor cells in an undifferentiated state.

In this seminar, I will introduce these mechanisms controlling gastric
differentiation and discuss the fundamental principles underlying
gastric epithelial homeostasis.

 
References:

1. Takada H, Sasagawa Y, Yoshimura M, Tanaka K, Iwayama Y, Hayashi T,
Isomura-Matoba A, Nikaido I, Kurisaki A.Single-cell transcriptomics
uncovers EGFR signaling-mediated gastric progenitor cell differentiation
in stomach homeostasis. Nat Commun. 2023 14(1):3750.

2. Noguchi TK, Ninomiya N, Sekine M, Komazaki S, Wang PC, Asashima M,
Kurisaki A.
Generation of stomach tissue from mouse embryonic stem cells. Nat Cell
Biol. 2015 17(8):984-993.

Speaker: Shuntaro Izawa (PostDoc, Max Planck Institute for Metabolism Research）

Title:Neural control of instinctive behaviors

Date&Time:  29 October (wed)　12：00-13：00

Venue:  Conference Room(1F), IMEG, Kumamoto University

※This seminar can also be attended through ZOOM. Please check the URL on “S-HIGO Cutting-Edge Seminar A, B” at Moodle.

https://md.kumamoto-u.ac.jp/course/view.php?id=120331

Abstract:

The hypothalamus acts as a regulatory center for instinctive behaviors such as sleep and metabolism. Advances in modern neuroscience technology have improved our understanding of the systems and mechanisms that underlie these behaviors.

Most hypothalamic neurons contain and release peptides and hormones, functioning as endocrine systems. Our research has focused on orexin peptide and melanin-concentrating hormone (MCH). Orexin promotes wakefulness and increases energy expenditure, while MCH induces REM sleep and conserves energy. In this presentation, I will discuss current studies on MCH and orexin neuronal systems, including their regulatory interactions.

References:

１．Izawa S, Fusca D, Jiang H, Heilinger C, Hausen AC, Wunderlich FT, Steuernagel L, Kloppenburg P, Brüning JC.

Orexin/hypocretin receptor 2 signaling in MCH neurons regulates REM sleep and insulin sensitivity.

Cell Reports. 44(2):115277, 2025

2．Izawa S, Yoneshiro T, Kondoh K, Nakagiri S, Okamatsu-Ogura Y, Terao A, Minokoshi Y, Yamanaka A, Kimura K.

Melanin-concentrating hormone-producing neurons in the hypothalamus regulate brown adipose tissue and thus contribute to energy expenditure.

Journal of Physiology. 600(4):815-827, 2022.

3．Izawa S, Chowdhury S, Miyazaki T, Mukai Y, Ono D, Inoue R, Ohmura Y, Mizoguchi H, Kimura K, Yoshioka M, Terao A, Kilduff TS, Yamanaka A.

REM sleep-active MCH neurons are involved in forgetting hippocampus-dependent memories.

Science. 365(6459): 1308-1313, 2019.