Speaker: Tsuyoshi Osawa (Associate Professor, Research Center for Advanced Science and Technology, the University of Tokyo)

Title: Cancer metabolism within the tumor microenvironments

Date&Time: 16 July (Thu)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University  On site + Zoom

※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:

Tumor microenvironments are critical for metabolic alteration thereby promoting tumor progression. However, how organelle dynamics controls cancer metabolism within the tumor microenvironments is not fully characterized to date. Here we demonstrate that Golgi and mitochondria dynamics may control cancer metabolism within the tumor microenvironments through comprehensive nutriomics analyses. Golgi disassembly was observed nutrient-starved cancer cells within the tumor microenvironment and stimulated golgi stress-mediated transcriptional activation. In addition, we found that acidic pH tumor microenvironment stimulated mitochondrial fission. We also found a novel mitochondrial fusion mechanism mediated by PIPs. Together, these results suggest the modulation of organelle dynamics within tumor microenvironments may become novel anti-cancer therapeutics to limit tumor progression.

Speaker: Nobuaki Fukuma (Research Associate, Columbia university medical center, Faculty of medicine, Cardiology)

Title: Forgotten no more: sex differences and right heart remodeling in heart failure -The best thing you can do is the Right thing-

Date&Time: 8 July (wed)　13：00-14：00

Venue: Conference Room(1F), IMEG, Kumamoto University  On site + Zoom

※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:

Despite decades of research works and expanded fields for heart failure research, the burden of heart failure has increased worldwide. As a key to unveil the heart failure mystery, I put the spotlight on the forgotten side of heart failure: the sex differences and right heart remodeling in heart failure. My presentation will cover the approach for assessing the female specific phenotypes and sex differences in the therapeutic effects for heart failure. Furthermore, talking about the trend in Columbia university, I focus on the right heart dysfunction contributing to heart failure, independent of lung or left heart remodeling. From the viewpoint of forgotten no more, I discuss how to connect the research questions from the bed side and the bench side.

Speaker: Tsuyoshi Kawabata (Associate Professor, Atomic Bomb Disease Institute, Nagasaki University)

Title: Coming soon

Date&Time: 1 July (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University  On site + Zoom

※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: Keiko Tanaka Yamamoto (Principal Researcher, Korea Institute of Science and Technology)

Title: Cerebellar regulation of chronic stress-induced depression

Date&Time: 24 June (wed)　12：00-13：00

Venue: Conference Room(1F), IMEG, Kumamoto University  On site + Zoom

※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:

The cerebellum is now recognized as a brain structure involved in a wide range of functions, including motor coordination and learning, cognitive processing, and emotional regulation. Although the precise mechanisms by which the cerebellum contributes to these functions remain to be fully elucidated, its broad projections to multiple brain regions suggest that cerebellar influences are mediated, at least in part, through modulation of specific neural circuits underlying these functions^1,2. One brain region targeted by output neurons from the deep cerebellar nuclei (DCN) is the ventral tegmental area (VTA), which is critically involved not only in reward and motivation, but also in stress responses. In line with the proposed role of cerebellar modulation of specific neural circuits, we found that DCN neurons projecting to the VTA (VTAp-DCN neurons) are activated during restraint stress (RS), and that their activity proactively regulates the development of chronic RS-induced depression-like behaviors³. We next investigated how the activity of VTAp-DCN neurons contributes to these behavioral alterations⁴. Repeated activation during chronic RS reduced vesicular glutamate transporter 2 (VGLUT2) expression in VTAp-DCN neurons innervating VTA dopamine neurons, resulting in decreased excitatory synaptic transmission onto VTA dopamine neurons and reduced dopamine release in the nucleus accumbens, a major target of VTA dopamine neurons. Notably, the reduction in VGLUT2 expression temporally coincided with the emergence of depression-like behaviors, suggesting a causal contribution to the behavioral alterations. Consistently, preventing the reduction in VGLUT2 expression through overexpression suppressed depression-like behaviors and restored both synaptic transmission and dopamine release. These findings indicate that repeated activation of VTAp-DCN neurons during chronic RS induces plastic changes characterized by reduced VGLUT2 expression, leading to depression-like behaviors through weakened excitatory transmission and impaired dopamine signaling. Thus, cerebellum-dependent presynaptic adaptations in the VTA provide a mechanistic link between chronic stress and depression-like behaviors.

References

1. Kim T., Park H., Jun S., Park J.Y., Yamamoto Y.*, Tanaka-Yamamoto K.* (2026). Bidirectional interactions between neuromodulatory systems and the cerebellum in brain function. Biobehav. Rev. 187:106716. doi: 10.1016/j.neubiorev.2026.106716.
2. Kang S., Jun S., Baek S.J., Park H., Yamamoto Y.*, Tanaka-Yamamoto K.* (2021). Recent advances in the understanding of specific efferent pathways emerging from the cerebellum. Neuroanat. 15:759948. doi: 10.3389/fnana.2021.759948.
3. Baek S.J., Park J.S., Kim J., Yamamoto Y., Tanaka-Yamamoto K. (2022). VTA-projecting cerebellar neurons mediate stress-dependent depression-like behaviors. eLife 11:e72981. doi: 10.7554/eLife.72981
4. Kang S., Kim T., Kim D., Baek S.J., McHugh T.J., Yamamoto Y.*, Tanaka-Yamamoto K.* (2026). Cerebellar induced VTA plasticity underlies chronic stress-induced depression-like behaviors.

Speaker: Masanori Hirashima（Professor, Division of Pharmacology School of Medicine, Dentistry and Health Sciences, Niigata University）

Title: Lymphatic vascular development and related diseases

Date&Time: 17 June (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:

Lymphatic vessels, together with blood vessels, form the body’s lifeline and play a vital role in maintaining fluid homeostasis, immune responses, lipid absorption and the removal of foreign substances. During development, lymphatic endothelial cells differentiate from venous endothelial cells to form lymph sacs, which fuse with one another to form the lymphatic network. In adults, the lymphatic network is separated from the vascular network in peripheral tissues, but it anastomoses with blood vessels near the venous angle in the neck, returning lymph collected from throughout the body to the veins. Abnormalities in the developmental process are closely linked to the development of pathological conditions and are responsible for conditions such as fetal nuchal edema and lymphatic malformations (lymphangiomas). Furthermore, if there are abnormalities in platelet activation triggered by contact with lymphatic endothelial cells, the lymphatic and vascular systems fail to separate correctly. In this seminar, focusing on these topics elucidated through the analysis of mouse models, I will introduce the molecular mechanisms of lymphangiogenesis and the pathologies arising from their abnormalities, and discuss the potential for vascular regulation based on these findings.

Cutting edge Seminar

Speaker: Takahiro Kuchimaru（Professor, Division of Bioconvergence, Center for Molecular Imaging, Jichi Medical University）

Title: Genetically-encoded bioluminescence/fluorescence tools for multiscale imaging of cellular events in deep animal tissues

Date&Time: 3 June (wed)　12：00-13：00 　Cancelled

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:

We have developed genetically-encoded bioluminescence/fluorescence tools for multiscale imaging of cellular events in deep animal tissues. Specifically, we have developed synthetic near-infrared bioluminescence reactions that surpass the natural reaction in sensitivity, enabling improved detection of targets in deep tissues (1-3). In addition, these near-infrared bioluminescence systems provide high temporal resolution, paving the way for molecular imaging modality of freely moving animals (4).
Noninvasive bioluminescence imaging in animal models has strong potential in combination with single-cell genetic profiling of tissue-comprising cells. In particular, cell-cell interactions play pivotal roles in tissue homeostasis and disease progression. These days, spatial single-cell transcriptomics has emerged as a powerful approach to study cell-cell interactions in animal tissues. However, current methods—primarily based on computational inference or tissue section–based analyses—often involve trade-offs between sequencing depth and spatial resolution. To bridge this gap, we developed sGRAPHIC, a genetic tool for fluorescently labeling cell-cell interactions in living tissues and isolating labeled cells for single-cell transcriptomics (5). This optical labeling-based omics approach can be further enhanced by integration with multi-omics analysis beyond transcriptomics.

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

Title: Integrated Understanding of Biological Systems for Disease Control

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:

Biological phenomena are dynamic systems shaped through the interaction between genetic and environmental factors. In this lecture, using cardiovascular disease as a model, I will present a new research framework that integrates genomics, single-cell and spatial omics, and clinical phenotypes to elucidate disease mechanisms at the molecular level and achieve a systems-level understanding of biological processes. Furthermore, I will discuss translational research strategies that leverage these insights to develop therapies targeting the molecular mechanisms underlying disease, thereby highlighting future directions for next-generation medical science that bridges basic research and clinical medicine.

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