Traditionally, it was believed that a child’s characteristics were determined solely by the DNA sequence inherited from the parents. However, in recent years, it has been suggested that when parents are exposed to environmental factors such as stress, disease, or aging, changes occur in the information regulating gene function in sperm or eggs, and these changes may affect subsequent generations. Despite these indications, there had been no direct evidence until now.

In this study, the research team developed a novel technology that modulates the functional state of specific gene regions in sperm without altering the DNA sequence. Using this technology, they reproduced in mouse sperm a gene regulatory state similar to that associated with Silver-Russell syndrome, a condition whose mechanism of onset has not been fully understood. As a result, they confirmed that these changes were inherited by the offspring after fertilization, leading to abnormalities in growth and physical characteristics.

This groundbreaking achievement not only advances our understanding of how disease-related changes in sperm can be transmitted to the next generation but also opens the door to future development of therapies aimed at restoring abnormal sperm states to normal.

For details of the research, please refer to the Gunma University Institute for Molecular and Cellular Regulation (IMCR) website.

■Title
Germline epigenome editing identifies H3K9me3 as a mediator of intergenerational DNA methylation recovery in mice

■Journal
Nature Communications(2025.12.25)
DOI　10.1038/s41467-025-67488-9

 ■Link
Gunma University “News”on Media Release(Original/Japanese)
Institute for Molecular and Cellular Regulation
Viral Vector Core, GIAR

In this study, the team searched for molecules that enhance the efficacy of PARP inhibitors and discovered that suppressing LIG1 strengthens therapeutic effects. The combination with an LIG1 inhibitor was shown to have the potential to inhibit tumor growth, offering promise as a new treatment option for prostate cancer.

■Title
Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer

Masaru Tani¹, Koji Hatano^1,＊, Yu Ishizuya¹, Toshiki Oka¹, Tomohiro Kanaki¹, Shunsuke Inoguchi¹, Akihiro Yoshimura¹, Yuki Horibe¹, Yutong Liu¹, Sassi Nesrine¹, Yohei Okuda¹, Akinaru Yamamoto¹, Toshihiro Uemura¹, Gaku Yamamichi¹, Takuji Hayashi¹, Yoshiyuki Yamamoto¹, Taigo Kato¹, Atsunari Kawashima¹, Takao Yamaguchi², Satoshi Obika², Kosuke Yusa³, Norio Nonomura¹, Keisuke Nimura^4,＊
＊corresponding authors
1　Department of Urology, The University of Osaka Graduate School of Medicine, Suita, Japan
2　Graduate School of Pharmaceutical Sciences, The Universityof Osaka, Suita, Japan
3　Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan
4　Division of Gene Therapy Science,Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Japan

■Journal
Cancer Science　(IF: 4.3)
DOI　10.1111/cas.70194

■Link
Dr.NIMURA Laboratory

This study is a collaboration between the Gunma University Initiative for Advanced Research (GIAR) and The University of Queensland School of Public Health , led by Professor Gita Mishra , Adjunct Professor of the International Open Laboratory.

Dr Kazue Nagai and Dr Hsin-Fang Chung analysed health data from more than 730,000 women across 15 studies conducted in Japan, Australia, United Kingdom, Netherlands, Sweden, United States, and China.

“Our findings show that Asian and Black women (including African American, Caribbean, other Black identities) have a markedly elevated risk of type 2 diabetes compared with Caucasian women in Australia, Europe, and the United States, and this risk is further amplified by higher BMI,” Dr Nagai said.

“South or Southeast Asian and Black women had the highest diabetes risk, reaching 25% by age 70. Japanese and Chinese women followed at around 18% and 12%, respectively, whereas Caucasian women had the lowest risk at 7%.”

“Even after accounting for differences in body weight or central obesity, South or Southeast Asian women had more than four times the diabetes risk compared with Caucasian women, while Japanese, Chinese, Black, and Mixed or Other women had twice the risk,” Dr Chung said.

“Asian and Black women showed a greater diabetes risk than Caucasian women at the same BMI, even within the normal BMI range, and this risk was substantially higher among those with overweight or obesity.”

“Among women with an obese BMI ≥30.0 kg/m², the risk for South or Southeast Asian women was 35-fold higher, followed by Black women (24-fold), Japanese women (20-fold), and Chinese women (14-fold), all exceeding the risk seen in Caucasian women (10-fold), compared with Caucasian women with a BMI of 18.5-22.9 kg/m².”

“This shows that ethnicity strongly influences diabetes risk, even at the same BMI.”

Senior author Professor Gita Mishra said this is the largest study to examine how ethnicity and body weight jointly affect type 2 diabetes risk in women, with particular representation of three Asian subgroups.

“Our findings suggest that Asian women, particularly South or Southeast Asians, may have unique risk profiles for type 2 diabetes.”

“This highlights the need for early, ethnicity-specific diabetes prevention strategies, prioritising South or Southeast Asian women, including those with normal or modestly elevated BMI,” Professor Mishra said.

The research was published in the journal Diabetes Care and used data from the International collaboration for a Life course Approach to reproductive health and Chronic disease Event (InterLACE) consortium.

■Publication Details:
Title: The Association Between Race/Ethnicity and Risk of Type 2 Diabetes in Women Varies by BMI: A Pooled Analysis of Individual Data From 15 Cohort Studies
Journal: Diabetes Care
DOI:　10.2337/dc25-1478
Publication date: December 2, 2025, 7:00 PM (Central Standard Time)- corresponds to December 3, 2025, 10:00 AM (Japan Standard Time)

■Contact Information:
Dr. Kazue Nagai
Associate Professor, Gunma University Center for Food Science and Wellness/
Gunma University Initiative for Advanced Research (GIAR)
Gunma University
Email: kazue-nagai [at] gunma-u.ac.jp

Gunma University Initiative for Advanced Research (GIAR)
GIAR Support Office, Gunma University
Email: kk-kensui4 [at] ml.gunma-u.ac.jp
(Please replace “#” with “@”.)

■Related Links
The University of Queensland School of Public Health
Gunma University Initiative for Advanced Research
Gunma University Center for Food Science and Wellness
Gunma University Media Release(Original/Japanese)
Gunma University “News” on Media Release(Original/Japanese)
“News” – Media Coverage (Original / Japanese)
*Some media links may become unavailable depending on the media outlet.*

Please see the article here.

■ Related Link
[Press Release]

In recent years, cancer immunotherapy has emerged as a promising treatment option alongside surgery, chemotherapy, and radiation. One major breakthrough—immune checkpoint inhibitors—has shown success even in hard-to-treat cancers. However, challenges remain, including the limited range of cancers that respond to such treatments.

The team had previously observed that injecting HVJ-E into tumors could slow cancer growth. When combined with immune-stimulating antibodies, it also reduced tumors in parts of the body not directly treated. Until now, the mechanism behind these effects was unclear. Their new study shows that HVJ-E causes cancer cells to produce ApoD. This protein alone can block signals that promote tumor growth. When combined with activated T cells, it also helps eliminate tumors at distant sites.

This discovery suggests a new pathway for developing broad-spectrum cancer immunotherapies that are not limited by cancer type—and may even be effective against metastatic cancers.

Figure: How HVJ-E and ApoD Suppress Tumors
HVJ-E stimulates ApoD production in cancer cells, blocking tumor growth. When paired with activated T cells, ApoD also helps shrink tumors at distant sites. (“Apod” in the image refers to Apolipoprotein D (ApoD).)

■Publication Details:
Title: HVJ-E links Apolipoprotein d to anti-tumor effects
Authors:
Airi Ishibashi^1,10,Noriko Ohta^2,10, Yuko Uegaki¹, Hidefumi Suzuki³,Katsuya Fukino², Yuuta Hisatomi¹, Atsushi Tanemura⁴, Riuko Ohashi⁵, Koji Kitamura^1,6, Kotaro Saga¹, Yasuhide Yoshimura¹, Satoko Inubushi¹, Kyoso Ishida^1,7, Yoko Ino⁸, Yayoi Kimura⁸, Kenjiro Sawada⁷, Tadashi Kimura⁷, Eiji Kiyohara⁴, Kosuke Yusa⁹, Hidehisa Takahashi³, Yasufumi Kaneda¹, and Keisuke Nimura^2,10,*
1　 Division of Gene Therapy Science, Department of Genome Biology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
2　 Division of Gene Therapy Science, Gunma University Initiative for Advanced Research, Gunma University, Maebashi, Gunma 371-8511, Japan
3　 Department of Molecular Biology, Graduate School of Medical Science, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
4　 Department of Dermatology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
5　 Division of Molecular and Diagnostic Pathology, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan
6　 Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
7　 Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
8　 Advanced Medical Research Center, Yokohama City University, Yokohama, Kanagawa 236-0004, Japan
9　 Stem Cell Genetics, Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto 606-8507, Japan
10　 These authors contributed equally to this work
*, Corresponding author

Journal: Journal for ImmunoTherapy of Cancer
DOI:　10.1136/jitc-2024-011442
Publication date: June 19, 2025, 5:00 PM (PST) – corresponds to June 20, 2025, 10:00 AM (JST)

■Funding:
This work was supported by the Center for Medical Research and Education, Graduate School of Medicine, Osaka University; research equipment shared in the MEXT Project for promoting public utilization of advanced research infrastructure (program for supporting the introduction of the new sharing system) Grant Number JPMXS0420600124, Gunma University; AMED grant number 18cm0106341h0001, 23ym0126809j0002, 24ym0126809j0003, 25ym0126809j0004, and 25ama221343h0001; JSPS KAKENHI grant number JP21K19408, JP21H05158, JP21H05160 and JP24H00633; JST Program for co-creating startup ecosystem, Grant Number JPMJSF2319; MEXT Promotion of Distinctive Joint Research Center Program Grant Number JPMXP0724020288 at the Advanced Medical Research Center, Yokohama City University; research grants from Bristol-Myers Squibb, The Osaka Community Foundation, and Osaka University Entrepreneurship Development Grant; and in part by the Osaka University Program for the Support of Networking among Present and Future Researchers.

■Contact Information:
Professor Keisuke Nimura
Division of Gene Therapy Science
Gunma University Initiative for Advanced Research (GIAR)
Gunma University
Email: nimura [at] gunma-u.ac.jp

■Related Links
Gunma University Initiative for Advanced Research(GIAR) Division of Gene Therapy Science Dr.NIMURA Laboratory
Gunma University Press Release(Original/Japanese)

Purine nucleotides and their derivatives play crucial roles in many cellular processes, making them essential metabolites for all living organisms. Purine nucleotides are synthesized through salvage or de novo pathways. De novo purine synthesis (DPS) is up-regulated under conditions of high purine demand to ensure the production of genetic materials and chemical energy, thereby supporting cell proliferation. However, the regulatory mechanisms governing DPS remain unclear. We herein show that PRPP amidotransferase (PPAT), the rate-limiting enzyme in DPS, forms dynamic and motile condensates in cells under a purine-depleted environment. The formation and maintenance of condensates requires phase separation, which is driven by target of rapamycin complex 1-induced ribosome biosynthesis. The self-assembly of PPAT molecules facilitates condensate formation, with intracellular PRPP and purine nucleotides both regulating this self-assembly. Moreover, molecular dynamics simulations suggest that clustering-mediated PPAT activation occurs through intermolecular substrate channeling. Cells unable to form PPAT condensates exhibit growth defects, highlighting the physiological importance of condensation. Disorders in the regulation of purine metabolism are associated with various diseases, such as cancer and hyperuricemia (gout). Therefore, detailed examinations of DPS, including this study, will provide insights into the molecular mechanisms underlying these diseases.

■Title
Phase separation of the PRPP amidotransferase into dynamic condensates promotes de novo purine synthesis in yeast

Masak Takaine^1*, Rikuri Morita², Yuto Yoshinari³ and Takashi Nishimura³
1　 GIAR, Gunma University, Maebashi, Japan, IMCR, Gunma University, Maebashi, Japan
2　 Center for Computational Sciences, University of Tsukuba, Ibaraki, Japan
3　 Laboratory of Metabolic Regulation and Genetics, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma, Japan
*, corresponding author

■Journal
PLOS Biology(IF 7.8)

DOI番号　10.1371/journal.pbio.3003111

■Link
Gunma University Initiative for Advanced Research(GIAR)
Institute for Molecular and Cellular Regulation(IMCR)
Gunma University Press Release(Original)
Center for Computational Sciences, University of Tsukuba

Please refer to below the for more details regarding the research.

■Title

Interstitial-fluid shear stresses induced by vertically oscillating head motion lower blood pressure in hypertensive rats and humans

■Journal

『Nature Biomedical Engineering』2023.07.07

DOI　10.1038/s41551-023-01061-x

 ■Link

Guraduate School of Medicine/ School of Medicine Faculty of Medicine(JP only)

GIAR Viral Vector Core

■Title

Effects of Ultrafine Single-Nanometer Oxygen Bubbles on Radiation Sensitivity in a Tumor-Bearing Mouse Model

Navchaa Gombodorj ^1,2,3,†, Takehiko Yokobori ^1,*,†, Nobutoshi Mutsuki ⁴, Bilguun Erkhem-Ochir ^1,5, Haruka Okami ⁵, Takayuki Asao ⁶, Hiroshi Saeki ⁵, Ken Shirabe ⁵ and, Dai Yamanouchi ^7,*

*Authors to whom correspondence should be addressed.^†These authors contributed equally to this work.

1　Division of Integrated Oncology Research, Gunma University Initiative for Advanced Research (GIAR), 3-39-22 Showamachi, Maebashi 371-8511, Japan

2　Department of Radiation Oncology, National Cancer Center, Ulaanbaatar 13370, Mongolia

3　Division of Referral and Primary Healthcare Services, Ministry of Health, Ulaanbaatar 14210, Mongolia

4　Sigma Technology Inc., 1-11-29 Sotono, Hitachinaka 312-0053, Japan

5　Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan

6　Gunma University Center for Mathematics and Data Science, 4-2 Aramaki, Maebashi 371-8510, Japan

7　Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI 53726, USA

■Journal

International Journal of Molecular Sciences　(IF 5.542)

DOI　10.3390/ijms23126838 (2022.6.20 published)

■Link

YOKOBORI Labolatory

■Title

Metabolomics in pulmonary medicine – extracting the most from your data

Stacey N. Reinke ¹, Romanas Chaleckis ^2,3, Craig E. Wheelock ^2,3,4

1 Centre for Integrative Metabolomics & Computational Biology, School of Science, Edith Cowan University, Perth, Australia.

2 Unit of Integrative Metabolomics, Institute of Environmental Medicine, Karolinska Institute, Stockholm, Sweden.

3 Gunma Initiative for Advanced Research (GIAR), Gunma University, Maebashi, Japan.

4 Department of Respiratory Medicine and Allergy, Karolinska University Hospital, Stockholm, Sweden.

■Journal

European Respiratory Journal (IF 16.67)

DOI　10.1183/13993003.00102-2022

■Link

Karolinska Institute (International Open Laboratry / Japan)

Karolinska Institute (Sweden)

■Title

DNA Damage Promotes HLA Class I Presentation by Stimulating a Pioneer Round of Translation Associated Antigen Production

Yuki Uchihara, Tiara Bunga Mayang Permata, Hiro Sato, Reika Kawabata-Iwakawa, Sayako Katada, Wenchao Gu, Sangeeta Kakoti, Motohiro Yamauchi, Reona Kato, Soehartati Gondhowiardjo, Naoki Hosen, Takaaki Yasuhara, and Atsushi Shibata*　* Corresponding author

■Journal

『Molecular Cell』 2022.5.19

DOI　10.1016/j.molcel.2022.04.030

■Link

SHIBATA Lab original Website

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