TMRC - Transborder Medical Research Center

Publication

Published:
22 Aug 2023

Biofilms Enhance Oil Degradation By Interfacial Tubulation

Researchers from the University of Tsukuba in collaboration with French researchers have discovered that oil-degrading bacteria, widely found in the ocean, grow around oil droplets forming dense communities at the oil-water interface. These communities cooperate to bend and buckle the oil interface, which enlarges its area and thereby allows more bacterial cells to come into direct contact with the oil for efficient oil degradation. … Read more –> (University of Tsukuba Website - Press Release)

→ Journal Publication - Science 【DOI】 10.1126/science.adf3345
Alcanivorax borkumensis Biofilms Enhance Oil Degradation By Interfacial Tubulation.

→ Research Outline (PDF In Japanese language)

Notice of Award

Published:
Aug 24 2023

2023 Young Investigator's Award presented to Assistant Professor Ryo Fujita of TMRC Division of Regenerative Medicine

Assistant Professor Ryo Fujita of Transborder Medical Research Center (TMRC) received the Young Investigator's Award Grand Prize at the 9th Annual Meeting of the Japanese Society of Muscular Research. The award was presented for his research on a new skeletal muscle stem cell regulatory mechanism using MyoD knock-in mice successfully created in 2023 (https://doi.org/10.1016/j.isci.2023.106592).

The Young Investigator's Award was presented for the best research at the 9th Annual Meeting of the Japanese Society of Muscle Biology. This award recognizes young investigators who have greatly contributed to research and development in the muscle biology field.

→ The 9th Annual Meeting of the Japan Muscular Dystrophy Society Website (website in Japanese language only)

→ Japan Muscular Dystrophy Association (website in Japanese language only)

Event

Published:
Posted July 28, 2023

TMRC Seminar Session - Christian Steidl of Centre for Lymphoid Cancer, British Columbia Cancer and Department of Pathology and Laboratory Medicine, University of British Columbia.

Transboder Medical Research Center Seminar (Event Completed)

Co-sponsored by: TSMM, Tsukuba Regenerative Medicine and Cell Therapy Conference

Presenter: Christian Steidl

Lymphoid Cancers: The importance of the tumor microenvironment

Centre for Lymphoid Cancer, British Columbia Cancer

Department of Pathology and Laboratory Medicine, University of British Columbia

Innovation Building, 8th Floor, University of Tsukuba.

July 19th, 2023,
18:00 - 19:00

Lymphoid cancers represent a heterogeneous group of neoplasms composed of malignant lymphoid cells with variable infiltration by non-neoplastic, mostly immune cells (tumor microenvironment).

The tumor microenvironment is increasingly recognized to play a pivotal role in the pathogenesis of many lymphoma subtypes. However, the clinical potential of an improved understanding of related biology remains largely untapped. Past discovery and functional studies by our group and others have pointed to the pathogenic importance of acquired immune privilege and altered cellular crosstalk between cells in the tumor microenvironment driven by somatic gene alterations.

The genomic changes discussed in this lecture can be broadly categorized according to the effect that they exert on the tumor microenvironment:

1) Loss or down-regulation of (surface) molecules leading to decreased immunogenicity of tumor cells;
2) Increased expression of surface molecules suppressing immune cell function;
3) Recruitment or induction of a regulatory cellular milieu. The discovery of gene mutations underlying immune privilege, downstream functional consequences, biomarker development and clinical rationales for therapeutic intervention will be discussed in the context of specific lymphoma subtypes.

Publication

Published:
Published in Cell Reports March 22 2023

Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination

Researchers from University of Tsukuba identify a family of proteins involved in the regulation of fast twitch muscle fibers for fast, powerful movements and reveal its impacts on the performance of physical activities

Tsukuba, Japan—Different types of exercise encourage the formation of different types of muscle fibers, or the cells that make up your muscles. Slow twitch muscle fibers support endurance activities like long-distance running, while fast twitch fibers are needed for short, powerful movements such as those involved in heavy weight lifting. Now, researchers in Japan have shed new light on a family of proteins involved in the development of these ... Read more (University of Tsukuba Press Release)...

→ Cell Reports DOI 10.1016/j.celrep.2023.112289
"Large Maf transcription factor family is a major regulator of fast type IIb myofiber determination."

→ Research Outline (PDF In Japanese language)

Publication

Published:
Published in Nature Feb 22 2023

Chemically defined cytokine-free expansion of human haematopoietic stem cells

Researchers from the University of Tsukuba develop a system for effectively growing large numbers of blood stem cells outside of the human body

Tsukuba, Japan—Hematopoietic stem cells (HSCs) are important immature blood cells in bone marrow that can be triggered to develop into any blood cell type. HSC transplants can be used to treat conditions where bone marrow is damaged and no longer able to produce healthy blood cells, but the widespread and safe use of HSCs is limited by barriers to cell growth and expansion in the lab (i.e. ex vivo). Now, a team led by researchers at the University of Tsukuba has established a novel culture system that supports long term ex vivo expansion of HSCs… Read More –> University of Tsukuba Research News Press Release

→ Nature 【DOI】 10.1038/s41586-023-05739-9
Chemically defined cytokine-free expansion of human haematopoietic stem cells.

→ Research Outline (PDF In Japanese language)

Publication

Published:
Published Feb 14 2023

Transcription factor c-Maf deletion improves streptozotocin-induced diabetic nephropathy by directly regulating Sglt2 and Glut2

(Note: Text has been auto translated from Japanese language.)

Chronic kidney disease is often caused by lifestyle-related diseases such as diabetes and hypertension. It is estimated to affect one in eight adults in Japan (approximately 13.3 million people). Chronic kidney disease progresses with few initial symptoms, and severe kidney dysfunction also significantly increases the risk of developing cardiovascular diseases such as myocardial infarction, stroke and arteriosclerosis; therefore, it is necessary to diagnose the disease at an earlier stage and start prevention and treatment prior to more severe conditions. However, there is currently no fundamental cure for advanced chronic kidney disease.

Research has previously discovered that the transcription factor (a protein that regulates gene expression) c-Maf regulates the expression of various membrane transporter proteins in the proximal tubules, which in addition to its therapeutic effect on diabetes, is also involved in renal damage and cardiovascular disease. c-Maf is also known to be involved in the regulation of organ development and immune cell function during embryonic development, but its function in adults is not well understood.

This study discovered that whole-body deletion of c-Maf in adult mice models of diabetes and associated renal damage ameliorated hyperglycemia and renal damage caused by diabetes and reduced oxidative stress in the kidney, is one of the main causes of renal damage. In other words, controlling timing of c-Maf expression could improve diabetes and chronic kidney disease, suggesting that targeting c-Maf could lead to the development of novel therapies for diabetes and chronic kidney disease.

→ JCI Insight DOI 10.1172/jci.insight.163306
"Transcription factor c-Maf deletion improves streptozotocin-induced diabetic nephropathy by directly regulating Sglt2 and Glut2."

→ Research Outline (PDF In Japanese language)

Publication

Published:
9 Dec 2022

Molecular signals within excitatory neurons regulate sleep

Elucidating the mechanism that determines the quantity and quality of sleep.

Sleep is necessary for everyone, but why sleep is needed at all is a mystery to this day. The research team focused on an enzyme (SIK3) which is key to solving this mystery. This enzyme regulates the chain of reactions in the brain involved in sleep, forming a molecular signal which regulates the quality and quantity of sleep. However, it was not known what kind of molecules and chains of molecules SIK3 forms for sleep regulation, or through which cells it is determined. In this study, the details of the chain (molecular signal) and the genes regulated by this molecular signal were clarified for the first time ever internationally.

We also found that the quality of sleep is regulated by excitatory neurons in the cortex and the quantity is regulated by excitatory neurons in the hypothalamus. We have also succeeded in further validating this molecular signal by using viral vectors to alter the quantity and quality of sleep in an acquired manner.

Sleep is essential for physical and mental health. Sleep disorders increase the risk of mental disorders, diabetes, heart disease, and dementia such as Alzheimer's disease, and decrease brain performance during the day. It is said that many people in Japan have sleep debt (mental and physical disorders associated with sleep deprivation). Through understanding the mechanisms that control the quantity and quality of sleep, it is expected to contribute to the development of new methods of sleep control and treatments for sleep disorders.

→ Journal Publication A - Nature 【DOI】 10.1038/s41586-022-05450-1
Kinase signalling in excitatory neurons regulates sleep quantity and depth.

→ Journal Publication B - Nature 【DOI】 10.1038/s41586-022-05510-6
A signaling pathway for transcriptional regulation of sleep amount in mice.

→ Research Outline (PDF In Japanese language)

Notice of Award

Published:
Dec 02 2022

2022 Chemo-Sero Therapeutic Research Institute Grant

Professor Mamiko Sakata-Yanagimoto (坂田-柳元　麻実子), who heads up the Advanced Hemato Oncology Laboratory in the TMRC Integrated Research Division, was selected for the Japan 2022 Chemo-Sero Therapeutic Research Institute Grant. The funding will go to support her lab's important research elucidating the pathogenesis of age pre-related malignant lymphoma.

→ "Kaketsuken" Press Release (PDF In Japanese language)
→ TMRC Integrated Research Division - Advanced Hemato Oncology Lab

Publication

Published:
Dec 01 2022

The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool.

Highlights:
• Quiescent muscle stem cells express the adhesion G-protein-coupled receptor Gpr116
• Gpr116-deficient muscle stem cells are incapable of maintaining quiescence
• The GPR116 Stachel agonist peptide prevents MuSC activation
• GPR116 signaling is mediated in part by nuclear activity of β-arrestin1

Skeletal muscle is populated with a reservoir of quiescent muscle stem cells (MuSCs), which regenerate the tissue after injury. Here, we show that the adhesion G-protein-coupled receptor Gpr116 is essential for long-term maintenance of the MuSC pool. Quiescent MuSCs express high levels of Gpr116, which is rapidly downregulated upon MuSC activation. MuSCs deficient for Gpr116 exhibit progressive depletion over time and are defective in self-renewal. Adhesion G-protein-coupled receptors contain an agonistic peptide sequence, called the “Stachel” sequence, within their long N-terminal ectodomains. Stimulation of MuSCs with the GPR116 Stachel peptide delays MuSC activation and differentiation. Stachel peptide stimulation of GPR116 leads to strong interaction with β-arrestins. Stimulation of GPR116 increases the nuclear localization of β-arrestin1, where it interacts with cAMP response element binding protein to regulate gene expression. Altogether, we propose a model by which GPR116 maintains the MuSC pool via nuclear functions of β-arrestin1.