Research Projects -
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Evaluate seed compounds for cancer suppressor SPRED2
2024.04 - 2025.03
AMED 橋渡し研究戦略的推進プログラム
Authorship：Principal investigator
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Development of DDS film and sheet materials that can be absorbed by the body
2024.04 - 2025.02
AMED 岡山県特別電源所在県科学技術振興事業
Authorship：Principal investigator
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Analysis of the mechanisms by which FPRs play a role in the immune regulation against cancer and organ transplantation and its application to treatments
Grant number：23K08070 2023.04 - 2026.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
吉村 禎造, 松川 昭博
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
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AI病理診断に向けた、組織切片の厚さの簡易計測法の開発と標準化技術の確立
Grant number：23K11895 2023.04 - 2026.03
日本学術振興会 科学研究費助成事業 基盤研究(C)
藤澤 真義, 大原 利章, 松川 昭博
Grant amount：\4160000 （ Direct expense: \3200000 、 Indirect expense：\960000 ）
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Mechanisms of cancer metastasis by message Capsule Exosomes
Grant number：22K19562 2022.06 - 2025.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Research (Exploratory) Grant-in-Aid for Challenging Research (Exploratory)
松川 昭博
Grant amount：\6500000 （ Direct expense: \5000000 、 Indirect expense：\1500000 ）
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Development of Visualized Submucosal Injectables Using Polysaccharide Derivatives to Address Unmet Needs
2022.04 - 2023.02
AMED 特別電源設置県科学技術振興事業研究委託事業
Authorship：Principal investigator
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Role of Spred2 in the pathogenesis of cancer and its application for cancer thepapy
Grant number：21H02988 2021.04 - 2024.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
松川 昭博, 伊藤 嘉浩, 吉村 禎造, 宮武 秀行, 阪口 政清
Grant amount：\17420000 （ Direct expense: \13400000 、 Indirect expense：\4020000 ）
１）がんの増殖・転移・幹細胞性獲得におけるSpred2の役割解明
肝がん細胞株（HepG2, HepG3, HLE）のSpred2をノックダウンすると細胞増殖能はいずれも増加した。最もSpred2発現の多いHepG2細胞からCRISPR-Cas9法でSpred2を消去した細胞を作製し、がん細胞特性を確認した。その結果、がん細胞増殖能・浸潤能は増加し、細胞形態は紡錘形に変化、上皮間葉移行と幹細胞性は増強した。これらの変化は、Spred2の過剰発現で逆転した。Spred2発現は非がん部に比較してがん部で低く（データベース上、および自験例の検討）、Spred2高発現肝がん患者では低発現患者に比べ有意に予後は高かった（データベース解析）。以上より、Spred2は、ERK経路を抑制し、がん細胞のEMTや幹細胞性を負に制御することを明らかにした（現在、論文投稿中）。
２）ヒトがん組織におけるSpred2の発現
275の尿路上皮腫瘍の検討結果から、Spred2 mRNA発現は高異型度非浸潤性乳頭状尿路上皮癌 (HGPUC)で最も高く、上皮内癌 (CIS)と浸潤性尿路上皮癌 (IUC)で低下し、Spred2タンパク発現はHGPUCで高く、CISとIUCではHGPUCに比べて減少していることを見いだした。HGPUCでSpred2膜発現を示すものはSpred2膜陰性のものと比べ、ERK活性化レベルとKi67 indexが有意に低かった。以上より、Spred2は非浸潤性膀胱癌の進展を調節する鍵であるものと考えられた（PLoS One. 2021 Nov 24;16(11):e0254289）。
３）Spred2のがん治療への応用
SPR-domainのみのSpred2に加え、さらなる短鎖Spred2プラスミドを６種類作製した。これらを用いて、全長Spred2との活性比較を行っている。 -
Multimodal cancer therapy by combination of immune therapy and targeting nanostructured carrier containing anti-cancer drug
Grant number：21H04965 2021.04 - 2024.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (A) Grant-in-Aid for Scientific Research (A)
伊藤 嘉浩, 上田 一樹, 鵜澤 尊規, 秋元 淳, 松川 昭博
Grant amount：\42380000 （ Direct expense: \32600000 、 Indirect expense：\9780000 ）
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アンメットニーズに応える多糖誘導体を用いた可視化粘膜下注入材の開発
2021.04 - 2022.03
岡山県特別電源所在県科学技術振興事業 岡山県特別電源所在県科学技術振興事業
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2000000
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Development of a new concept of embolization material for colonic diverticulosis
2020.04 - 2021.03
AMED 橋渡し研究戦略的推進プログラム
Authorship：Principal investigator
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大腸憩室症に対する新発想の塞栓材開発
2020.04 - 2021.03
橋渡し研究戦略的推進プログラム 橋渡し研究戦略的推進プログラム シーズA
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2000000
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リン酸化プルランの大量・精密製造技術の確立と短期骨再生を可能とするペースト状人工骨の開発
2019.04 - 2022.03
経済産業省 戦略的基盤技術高度化支援事業補助金
Authorship：Coinvestigator(s) Grant type：Competitive
Grant amount：\130000000
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Development of transplanted lung function-preserving method using a mouse model focusing on the anti-inflammatory related molecule Spred2
Grant number：19K09306 2019.04 - 2022.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Yamane Masaomi
Grant amount：\4420000 （ Direct expense: \3400000 、 Indirect expense：\1020000 ）
A lung injury experiment using a thoracotomy and clamp model was also performed using Spred2 knockout mice and transgenic mice that are Spred2 gene overexpressing mice. Histological images by RT-PCR and H-E staining and arterial gas analysis were performed and evaluated as preliminary experiments, but no difference was observed. Furthermore, the expression level was confirmed by Western blotting using an anti-mouse SPRED2 antibody, but no difference was observed in the preliminary experiment.
Overexpression of Spred2 at protein and mRNA levels could not be confirmed in Spred2 transgenic mice and conditional knockout mice specifically deficient in bone marrow-derived cells, compared with wild-type in experiments using a hilar clamp model. No significant difference was found in ischemia-reperfusion injury. -
多糖誘導体を用いた高操作性可視化粘膜下注入材の開発
2019.04 - 2020.03
岡山県特別電源所在県科学技術振興事業 岡山県特別電源所在県科学技術振興事業
Authorship：Principal investigator Grant type：Competitive
Grant amount：\2000000
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Inhibition of formylpeptide receptors for treatment of breast cancer
Grant number：18K08571 2018.04 - 2021.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
Yoshimura Teizo
Grant amount：\2600000 （ Direct expense: \2000000 、 Indirect expense：\600000 ）
Tumor infiltrating leukocytes play an important role in the progression of cancer. In this study, we examined the role of the classical chemoattractant receptor Fpr expressed by non-tumor cells in the progression of breast cancer using a transplantable 4T1 mouse breast cancer model. Tumors grew at a similar rate in both strains at the injected sites; however, lung metastases were significantly reduced in Fpr2-deficient mice independently of the chemokine MCP-1 because serum MCP-1 levels were similar between tumor-bearing WT and Fpr2-deficient mice. In tumors of Fpr2-deficient mice, the development of blood vessels was weaker and necrosis of tumor tissue was more apparent. Ly6G+ neutrophils were detected mainly in the peripheral area and did not infiltrate inside tumors. Thus, Fpr2+ neutrophils appear to play a role in the progression of 4T1 breast cancer. Studies focusing on Fprs may lead to the identification of new targets and a potential prevention of breast cancer metastasis.
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Grant number：17K10930 2017.04 - 2020.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
TANAKA Masato
Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）
The phosphorylated pullulan developed by the applicants is a functional polysaccharide derivative that firmly adheres to apatite, which is an inorganic component of living hard tissue. We aimed to develop a film-shaped phosphorylated pullulan that can be expected as a bioadhesive and a carrier for drug delivery, and to combine it with BMP to develop a safe and low-cost bone fusion promoter. The bone formation ability of the rat posterior lateral fixation model was examined, and good bone formation was observed in the BMP-2-added phosphorylated pullulan film group. In this study, phosphorylated pullulan was considered to have extremely low cytotoxicity in bone formation, and could be safely applied clinically.
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Grant number：16H05310 2016.04 - 2020.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B) Grant-in-Aid for Scientific Research (B)
Ito Toshihiro
Grant amount：\16770000 （ Direct expense: \12900000 、 Indirect expense：\3870000 ）
Patients who have a chronic respiratory disease have a very high risk of respiratory infection due to viruses and bacteria, and it is necessary to elucidate the pathological condition and molecular mechanism and identify the factors that affect each other's diseases. In this study, we focused on SET domain, bifurcated 2 (SETDB2), which is one of the histone H3K9 (9th lysine) methylase, and the expression of SETDB2 showed a significant increase in the chronic respiratory disease model. The importance of SETDB2 in respiratory diseases was clarified by increasing the expression in chronic respiratory diseases and respiratory infections and by indicating the role of SETDB2 in pathological conditions.
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Challenge to novel antiviral strategy by suppressing signal transduction pathway
Grant number：16K15258 2016.04 - 2019.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Challenging Exploratory Research Grant-in-Aid for Challenging Exploratory Research
MATSUKAWA AKIHIRO, Yang Xu, Sun Cuiming, Gao Tong, Miyatake Hideyuki, Kondo Masayuki
Grant amount：\3640000 （ Direct expense: \2800000 、 Indirect expense：\840000 ）
In this study, we clarified the mechanism of viral infection from the viewpoint of Ras-Raf-ERK / MAPK and its endogenous suppressor Spred2, and we challenged the antiviral strategy via ERK suppression by supplementation of Spred2. Activation of ERK-MAPK and viral infection were suppressed by Spred2 gene transfer. There was no difference in virus infection in Spred2 overexpressing mice, suggesting that the endogenous Spred2 is sufficient to inhibit the infection. Cell-penetrating Spred2 created in this study failed to inhibit ERK activation, however, supplementation of functional Spred2 protein may become a new antiviral drug.
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Grant number：16K10823 2016.04 - 2019.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Arataki Shinya
Grant amount：\4680000 （ Direct expense: \3600000 、 Indirect expense：\1080000 ）
We analyzed the usefulness of new intervertebral disc regeneration treatment using intervertebral disc degeneration model of rats in combination with cultured disc annulus fibrosus cells and novel, visible light-induced, rapidly cross-linkable gelatin scaffold. Transplanted cells were found to engraft on the transplanted site, but regeneration of the annulus fibrosus was not identified. As a growth factor used for regenerative therapy, we studied BMP-7 that has been reported in the past, but this study suggested the possibility of contribution to degeneration in the annulus fibrosus.
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Grant number：16K10822 2016.04 - 2019.03
Japan Society for the Promotion of Science Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C) Grant-in-Aid for Scientific Research (C)
Sugimoto Yoshihisa
Grant amount：\4810000 （ Direct expense: \3700000 、 Indirect expense：\1110000 ）
We analyzed the usefulness of novel spinal cord injury (SCI) treatment using engineered hepatocyte growth factor with a collagen biding domain (CBD-HGF) and visible light-induced, rapidly cross-linkable gelatin in spinal cord injury model of mice. In motor recovery and immunohistochemical analyses, therapeutic effects were identified. CBD-HGF combined with the hydrogel scaffold may be promising for the treatment of serious SCI. About neural stem cells (NCS), we established stem cell culture technology using mouse embryos, however we could not reach transplantation into spinal cord injury model. We plan to continue the study by combining these methods.