Misa Okumura-Hirono, Tetsuya Bando, Yoshimasa Hamada, Motoo Araki and Hideyo Ohuchi : ROS produced by Dual oxidase regulate cell proliferation and haemocyte migration during leg regeneration in the cricket, Development, 152, 22, 2025.
(Summary)
Many animals regenerate lost body parts through several signalling pathways; however, the triggers that initiate regeneration remain unclear. In the present study, we focused on the role of reactive oxygen species (ROS) produced by the NADPH oxidase Dual oxidase (Duox) during cricket leg regeneration. The results showed that ROS levels were upregulated during leg regeneration and decreased by DuoxRNAi. In DuoxRNAi nymphs, wound closure and scab formation were incomplete 2 days after amputation, and hypertrophy occurred in the distal region of the regenerating legs at 5 days after amputation. In addition, the hypertrophic phenotype was induced by DuoxARNAi and NADPH oxidase inhibitor treatment. During hypertrophy, haemocytes, including plasmatocytes, oenocytoids and granulocytes, accumulated. Proliferation of haemocytes in regenerating legs was not increased by DuoxRNAi; however, haemocyte accumulation was regulated by the Spatzle (Spz) family molecules, which are Toll receptor ligands. As the exoskeleton of DuoxRNAi nymphs was thinner than that of the control, excessive haemocyte accumulation can cause hypertrophy in DuoxRNAi nymphs. Thus, Duox-derived ROS are involved in wound healing and haemocyte accumulation through the Spz/Toll signalling pathway during leg regeneration in crickets.
Hanif ALi, Mone Yamanishi, Rumana Yesmin Hasi, MD Majidul Islam, Yoshimasa Hamada, Masato Miyake, Seiichi Oyadomari, Emi Kiyokage, Kazunori Toida, Ryushi Kawakami, Mutsumi Aihara and Tamotsu Tanaka : Different effects of Lorenzos oil components against very long-chain fatty acid-induced endoplasmic reticulum stress in peroxisome-deficient CHO cells., Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 1870, 7, 159670, 2025.
(Summary)
Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder caused by mutations in the ABCD1 gene, leading to the accumulation of very long-chain fatty acids (VLCFAs). The accumulation of saturated VLCFAs, such as C24:0 and C26:0, is believed to impair myelination. A mixture of C18:1 (oleic acid) and C22:1 (erucic acid), known as Lorenzo's oil, has been used to reduce these saturated VLCFAs. However, despite lowering saturated VLCFA levels, Lorenzo's oil proved ineffective in preventing neurological symptoms. Previously, we found that VLCFA-induced apoptosis is prevented by C18:1 supplementation in peroxisome-deficient Chinese Hamster Overy (CHO) cells. In this study, we investigated the mechanism underlying the rescue effect of C18:1 and examined the effect of C22:1, another component of Lorenzo's oil. Supplementation with C18:1 completely rescued the cells from VLCFA-induced apoptosis. In contrast, C22:1 enhanced VLCFA cytotoxicity and diminished the protective effect of C18:1. We found that VLCFA-induced apoptosis is mediated via the endoplasmic reticulum (ER) stress response possibly by disruption of ER structure, whereas C18:1 attenuated this ER stress. Quantitative lipidomics revealed that VLCFAs were predominantly incorporated into phosphatidylcholine (PC), accompanied by a significant reduction in PC species containing C18:1. Among these, PC 36:2 (18:1/18:1) showed a pattern of change that correlated with cellular viability. These results indicate that C18:1, but not C22:1, protects peroxisome-deficient CHO cells by ameliorating the ER stress response, likely through improving ER structure distorted by VLCFA accumulation.
Tsutomu Miwata, Hidetaka Suga, Kazuki Mitsumoto, Jun Zhang, Yoshimasa Hamada, Mayu Sakakibara, Mika Soen, Hajime Ozaki, Tomoyoshi Asano, Takashi Miyata, Yohei Kawaguchi, Yoshinori Yasuda, Tomoko Kobayashi, Mariko Sugiyama, Takeshi Onoue, Daisuke Hagiwara, Shintaro Iwama, Seiichi Oyadomari and Hiroshi Arima : Simplified drug efficacy evaluation system for vasopressin neurodegenerative disease using mouse disease-specific induced pluripotent stem cells., Peptides, 173, 2024.
(Summary)
Familial neurohypophyseal diabetes insipidus (FNDI) is a degenerative disorder in which vasopressin-secreting neurons degenerate over time due to the production of mutant proteins. We have demonstrated therapeutic effects of chemical chaperones in an FNDI mouse model, but the complexity and length of this evaluation were problematic. In this study, we established disease-specific mouse induced pluripotent stem cells (iPSCs) from FNDI-model mice and differentiated vasopressin neurons that produced mutant proteins. Fluorescence immunostaining showed that chemical chaperones appeared to protect vasopressin neurons generated from iPSCs derived from FNDI-model mice. Although KCL stimulation released vasopressin hormone from vasopressin neurons generated from FNDI-derived iPSCs, vasopressin hormone levels did not differ significantly between baseline and chaperone-added culture. Semi-quantification of vasopressin carrier protein and mutant protein volumes in vasopressin neurons confirmed that chaperones exerted a therapeutic effect. This research provides fundamental technology for creating in vitro disease models using human iPSCs and can be applied to therapeutic evaluation of various degenerative diseases that produce abnormal proteins.
Jirapat Namkaew, Jun Zhang, Norio Yamakawa, Yoshimasa Hamada, Kazue Tsugawa, Miho Oyadomari, Masato Miyake, Toyomasa Katagiri and Seiichi Oyadomari : Repositioning of mifepristone as an integrated stress response activator to potentiate cisplatin efficacy in non-small cell lung cancer., Cancer Letters, 582, 2023.
(Summary)
Lung cancer, primarily non-small-cell lung cancer (NSCLC), is a significant cause of cancer-related mortality worldwide. Cisplatin-based chemotherapy is a standard treatment for NSCLC; however, its effectiveness is often limited due to the development of resistance, leading to NSCLC recurrence. Thus, the identification of effective chemosensitizers for cisplatin is of paramount importance. The integrated stress response (ISR), activated by various cellular stresses and mediated by eIF2α kinases, has been implicated in drug sensitivity. ISR activation globally suppresses protein synthesis while selectively promoting the translation of ATF4 mRNA, which can induce pro-apoptotic proteins such as CHOP, ATF3, and TRIB3. To expedite and economize the development of chemosensitizers for cisplatin treatment in NSCLC, we employed a strategy to screen an FDA-approved drug library for ISR activators. In this study, we identified mifepristone as a potent ISR activator. Mifepristone activated the HRI/eIF2α/ATF4 axis, leading to the induction of pro-apoptotic factors, independent of its known role as a synthetic steroid. Our in vitro and in vivo models demonstrated mifepristone's potential to inhibit NSCLC re-proliferation following cisplatin treatment and tumor growth, respectively, via the ISR-mediated cell death pathway. These findings suggest that mifepristone, as an ISR activator, could enhance the efficacy of cisplatin-based therapy for NSCLC, highlighting the potential of drug repositioning in the search for effective chemosensitizers.
(Keyword)
Humans / Carcinoma, Non-Small-Cell Lung / Cisplatin / Lung Neoplasms / Mifepristone / Drug Repositioning / Signal Transduction / Cell Line, Tumor / Drug Resistance, Neoplasm
Mitsuaki Sobajima, Masato Miyake, Yoshimasa Hamada, Kazue Tsugawa, Miho Oyadomari, Ryota Inoue, Jun Shirakawa, Hiroshi Arima and Seiichi Oyadomari : The multifaceted role of ATF4 in regulating glucose-stimulated insulin secretion., Biochemical and Biophysical Research Communications, 611, 165-171, 2022.
(Summary)
Stress-inducible transcription factor ATF4 is essential for survival and identity of β-cell during stress conditions. However, the physiological role of ATF4 in β-cell function is not yet completely understood. To understand the role of ATF4 in glucose-stimulated insulin secretion (GSIS), β-cell-specific Atf4 knockout (βAtf4KO) mice were phenotypically characterized. Insulin secretion and mechanistic analyses were performed using islets from control Atf4f/f and βAtf4KO mice to assess key regulators for triggering and amplifying signals for GSIS. βAtf4KO mice displayed glucose intolerance due to reduced insulin secretion. Moreover, βAtf4KO islets exhibited a decrease in both the insulin content and first-phase insulin secretion. The analysis of βAtf4KO islets showed that ATF4 is required for insulin production and glucose-stimulated ATP and cAMP production. The results demonstrate that ATF4 contributes to the multifaceted regulatory process in GSIS even under stress-free conditions.
Tetsuya Bando, Misa Okumura, Yuki Bando, Marou Hagiwara, Yoshimasa Hamada, Yoshiyasu Ishimaru, Taro Mito, Eri Kawaguchi, Takeshi Inoue, Kiyokazu Agata, Sumihare Noji and Hideyo Ohuchi : Toll signalling promotes blastema cell proliferation during cricket leg regeneration via insect macrophages., Development, 149, 8, 2022.
(Summary)
Hemimetabolous insects, such as the two-spotted cricket Gryllus bimaculatus, can recover lost tissues, in contrast to the limited regenerative abilities of human tissues. Following cricket leg amputation, the wound surface is covered by the wound epidermis, and plasmatocytes, which are insect macrophages, accumulate in the wound region. Here, we studied the function of Toll-related molecules identified by comparative RNA sequencing during leg regeneration. Of the 11 Toll genes in the Gryllus genome, expression of Toll2-1, Toll2-2 and Toll2-5 was upregulated during regeneration. RNA interference (RNAi) of Toll, Toll2-1, Toll2-2, Toll2-3 or Toll2-4 produced regeneration defects in more than 50% of crickets. RNAi of Toll2-2 led to a decrease in the ratio of S- and M-phase cells, reduced expression of JAK/STAT signalling genes, and reduced accumulation of plasmatocytes in the blastema. Depletion of plasmatocytes in crickets using clodronate also produced regeneration defects, as well as fewer proliferating cells in the regenerating legs. Plasmatocyte depletion also downregulated the expression of Toll and JAK/STAT signalling genes in the regenerating legs. These results suggest that Spz-Toll-related signalling in plasmatocytes promotes leg regeneration through blastema cell proliferation by regulating the Upd-JAK/STAT signalling pathway.
Keisuke Kitakaze, Miho Oyadomari, Jun Zhang, Yoshimasa Hamada, Yasuhiro Takenouchi, Kazuhito Tsuboi, Mai Inagaki, Masanori Tachikawa, Yoshio Fujitani, Yasuo Okamoto and Seiichi Oyadomari : ATF4-mediated transcriptional regulation protects against β-cell loss during endoplasmic reticulum stress in a mouse model., Molecular Metabolism, 54, 2021.
(Summary)
We conclude that transcriptional regulation by ATF4 maintains β-cell identity via ISR modulation. This mechanism provides a promising target for the treatment of diabetes.
The integrated stress response (ISR) is one of the most important cytoprotective mechanisms and is integrated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α). Four eIF2α kinases, heme-regulated inhibitor (HRI), double-stranded RNA-dependent protein kinase (PKR), PKR-like endoplasmic reticulum kinase (PERK), and general control nonderepressible 2 (GCN2), are activated in response to several stress conditions. We previously reported that nanosecond pulsed electric fields (nsPEFs) are a potential therapeutic tool for ISR activation. In this study, we examined which eIF2α kinase is activated by nsPEF treatment. To assess the responsible eIF2α kinase, we used previously established eIF2α kinase quadruple knockout (4KO) and single eIF2α kinase-rescued 4KO mouse embryonic fibroblast (MEF) cells. nsPEFs 70 ns in duration with 30 kV/cm electric fields caused eIF2α phosphorylation in wild-type (WT) MEF cells. On the other hand, nsPEF-induced eIF2α phosphorylation was completely abolished in 4KO MEF cells and was recovered by HRI overexpression. CM-H2DCFDA staining showed that nsPEFs generated reactive oxygen species (ROS), which activated HRI. nsPEF-induced eIF2α phosphorylation was blocked by treatment with the ROS scavenger N-acetyl-L-cysteine (NAC). Our results indicate that the eIF2α kinase HRI is responsible for nsPEF-induced ISR activation and is activated by nsPEF-generated ROS.
M Alexandra Stevens, Michael Xiang, N Lisa Heppler, Isidora Tošić, Kevin Jiang, O Jaime Munoz, S Amos Gaikwad, M Terzah Horton, Xin Long, Padmini Narayanan, L Elizabeth Seashore, C Maci Terrell, Raushan Rashid, J Michael Krueger, E Alicia Mangubat-Medina, T Zachary Ball, Pavel Sumazin, R Sarah Walker, Yoshimasa Hamada, Seiichi Oyadomari, S Michele Redell and A David Frank : Atovaquone is active against AML by upregulating the integrated stress pathway and suppressing oxidative phosphorylation., Blood Advances, 3, 24, 4215-4227, 2019.
(Summary)
Atovaquone, a US Food and Drug Administration-approved antiparasitic drug previously shown to reduce interleukin-6/STAT3 signaling in myeloma cells, is well tolerated, and plasma concentrations of 40 to 80 µM have been achieved with pediatric and adult dosing. We conducted preclinical testing of atovaquone with acute myeloid leukemia (AML) cell lines and pediatric patient samples. Atovaquone induced apoptosis with an EC50 <30 µM for most AML lines and primary pediatric AML specimens. In NSG mice xenografted with luciferase-expressing THP-1 cells and in those receiving a patient-derived xenograft, atovaquone-treated mice demonstrated decreased disease burden and prolonged survival. To gain a better understanding of the mechanism of atovaquone, we performed an integrated analysis of gene expression changes occurring in cancer cell lines after atovaquone exposure. Atovaquone promoted phosphorylation of eIF2α, a key component of the integrated stress response and master regulator of protein translation. Increased levels of phosphorylated eIF2α led to greater abundance of the transcription factor ATF4 and its target genes, including proapoptotic CHOP and CHAC1. Furthermore, atovaquone upregulated REDD1, an ATF4 target gene and negative regulator of the mechanistic target of rapamycin (mTOR), and caused REDD1-mediated inhibition of mTOR activity with similar efficacy as rapamycin. Additionally, atovaquone suppressed the oxygen consumption rate of AML cells, which has specific implications for chemotherapy-resistant AML blasts that rely on oxidative phosphorylation for survival. Our results provide insight into the complex biological effects of atovaquone, highlighting its potential as an anticancer therapy with novel and diverse mechanisms of action, and support further clinical evaluation of atovaquone for pediatric and adult AML.
Keisuke Kitakaze, Shusuke Taniuchi, Eri Kawano, Yoshimasa Hamada, Masato Miyake, Miho Oyadomari, Hirotatsu Kojima, Hidetaka Kosako, Tomoko Kuribara, Suguru Yoshida, Takamitsu Hosoya and Seiichi Oyadomari : Cell-based HTS identifies a chemical chaperone for preventing ER protein aggregation and proteotoxicity., eLife, 8, e43302, 2019.
(Summary)
]benzothiazole derivatives (IBTs) as chemical chaperones in a cell-based high-throughput screen. Biochemical and chemical biology approaches revealed that IBT21 directly binds to unfolded or misfolded proteins and inhibits protein aggregation. Finally, IBT21 prevented cell death caused by chemically induced ER stress and by a proteotoxin, an aggression-prone prion protein. Taken together, our data show the promise of IBTs as potent chemical chaperones that can ameliorate diseases resulting from protein aggregation under ER stress.
Tetsuya Bando, Taro Mito, Yoshimasa Hamada, Yoshiyasu Ishimaru, Sumihare Noji and Hideyo Ohuchi : Molecular mechanisms of limb regeneration: Insights from regenerating legs of the cricket gryllus bimaculatus, The International Journal of Developmental Biology, 62, 6-8, 559-569, 2018.
(Summary)
This review summarizes recent advances in leg regeneration research, focusing on the cricket Gryllus bimaculatus. Recent studies have revealed molecular mechanisms on blastema formation, establishment of positional information, and epigenetic regulation during leg regeneration. Especially, these studies have provided molecular bases in classical conceptual models such as the polar coordinate model, the intercalation model, the boundary model, the steepness model, etc., which were proposed to interpret regeneration processes of the cockroach legs. When a leg is amputated, a blastema is formed through the activation of the Janus-kinase (Jak)/Signal-Transduction-and-Activator-of-Transcription (STAT) pathway. Subsequently, the Hedgehog/Wingless/Decapentaplegic/Epidermal-growth-factor pathways instruct distalization in the blastema, designated as the molecular boundary model. Downstream targets of this pathway are transcription factors Distal-less (Dll) and dachshund (dac), functioning as key regulators of proximodistal pattern formation. Dll and dac specify the distal and proximal regions in the blastema, respectively, through the regulation of tarsal patterning genes. The expression of leg patterning genes during regeneration may be epigenetically controlled by histone H3K27 methylation via Enhancer-of-zeste and Ubiquitously-transcribed-tetratricopeptide-repeat-gene-X-chromosome. For the molecular mechanism of intercalation of the missing structures between the amputated position and the most distal one, Dachsous/Fat (Ds/Ft) steepness model has been proposed, in which the Ds/Ft pathway maintains positional information and determines leg size through dac expression. This model was theoretically verified to interpret the experimental results obtained with cricket legs. Availability of whole-genome sequence information, regeneration-dependent RNA interference, and genome editing technique will have the cricket be an ideal model system to reveal gene functions in leg regeneration.
(Keyword)
Distalization / Gryllus bimaculatus / Intercalation / Leg regeneration / Steepness model
Yoshimasa Hamada, Atsushi Tokuoka, Tetsuya Bando, Hideyo Ohuchi and Kenji Tomioka : Enhancer of zeste plays an important role in photoperiodic modulation of locomotor rhythm in the cricket, Gryllus bimaculatus., Zoological Letters, 2, 2016.
(Summary)
These results suggest that histone modification by Gb'E(z) is involved in photoperiodic modulation of the G. bimaculatus circadian rhythm.
Yoshimasa Hamada, Tetsuya Bando, Taro Nakamura, Yoshiyasu Ishimaru, Taro Mito, Sumihare Noji, Kenji Tomioka and Hideyo Ohuchi : Leg regeneration is epigenetically regulated by histone H3K27 methylation in the cricket Gryllus bimaculatus, Development, 142, 17, 2916-2927, 2015.
(Summary)
Hemimetabolous insects such as the cricket Gryllus bimaculatus regenerate lost tissue parts using blastemal cells, a population of dedifferentiated proliferating cells. The expression of several factors that control epigenetic modification is upregulated in the blastema compared with differentiated tissue, suggesting that epigenetic changes in gene expression might control the differentiation status of blastema cells during regeneration. To clarify the molecular basis of epigenetic regulation during regeneration, we focused on the function of the Gryllus Enhancer of zeste [Gb'E(z)] and Ubiquitously transcribed tetratricopeptide repeat gene on the X chromosome (Gb'Utx) homologues, which regulate methylation and demethylation of histone H3 lysine 27 (H3K27), respectively. Methylated histone H3K27 in the regenerating leg was diminished by Gb'E(z)(RNAi) and was increased by Gb'Utx(RNAi). Regenerated Gb'E(z)(RNAi) cricket legs exhibited extra leg segment formation between the tibia and tarsus, and regenerated Gb'Utx(RNAi) cricket legs showed leg joint formation defects in the tarsus. In the Gb'E(z)(RNAi) regenerating leg, the Gb'dac expression domain expanded in the tarsus. By contrast, in the Gb'Utx(RNAi) regenerating leg, Gb'Egfr expression in the middle of the tarsus was diminished. These results suggest that regulation of the histone H3K27 methylation state is involved in the repatterning process during leg regeneration among cricket species via the epigenetic regulation of leg patterning gene expression.
Tetsuya Bando, Yoshiyasu Ishimaru, Takuro Kida, Yoshimasa Hamada, Yuji Matsuoka, Taro Nakamura, Hideyo Ohuchi, Sumihare Noji and Taro Mito : Analysis of RNA-seq data reveals involvement of JAK/STAT signalling during leg regeneration in the cricket Gryllus bimaculatus, Development, 140, 5, 959-964, 2013.
(Summary)
In the cricket Gryllus bimaculatus, missing distal parts of the amputated leg are regenerated from the blastema, a population of dedifferentiated proliferating cells that forms at the distal tip of the leg stump. To identify molecules involved in blastema formation, comparative transcriptome analysis was performed between regenerating and normal unamputated legs. Components of JAK/STAT signalling were upregulated more than twofold in regenerating legs. To verify their involvement, Gryllus homologues of the interleukin receptor Domeless (Gb'dome), the Janus kinase Hopscotch (Gb'hop) and the transcription factor STAT (Gb'Stat) were cloned, and RNAi was performed against these genes. Gb'dome(RNAi), Gb'hop(RNAi) and Gb'Stat(RNAi) crickets showed defects in leg regeneration. Blastema expression of Gb'cyclinE was decreased in the Gb'Stat(RNAi) cricket compared with that in the control. Hyperproliferation of blastema cells caused by Gb'fat(RNAi) or Gb'warts(RNAi) was suppressed by RNAi against Gb'Stat. The results suggest that JAK/STAT signalling regulates blastema cell proliferation during leg regeneration.
Tetsuya Bando, Yoshimasa Hamada, Kazuki Kurita, Taro Nakamura, Taro Mito, Hideyo Ohuchi and Sumihare Noji : Lowfat, a mammalian Lix1 homologue, regulates leg size and growth under the Dachsous/Fat signaling pathway during tissue regeneration, Developmental Dynamics, 240, 6, 1440-1453, Apr. 2011.
(Summary)
In the cricket Gryllus bimaculatus, missing distal parts of amputated legs are regenerated from blastemas based on positional information. The Dachsous/Fat (Ds/Ft) signaling pathway regulates blastema cell proliferation and positional information along the longitudinal axis during leg regeneration. Herein, we show that the Gryllus homologue of Lowfat (Gb'Lft), which modulates Ds/Ft signaling in Drosophila, is involved in leg regeneration. Gb'lft is expressed in regenerating legs, and RNAi against Gb'lft (Gb'lft(RNAi)) suppressed blastema cell hyperproliferation caused by Gb'ft(RNAi) or Gb'ds(RNAi) but enhanced that caused by Gb'kibra(RNAi) or Gb'warts(RNAi). In Gb'lft(RNAi) nymphs, missing parts of amputated legs were regenerated, but the length of the regenerated legs was shortened depending on the position of the amputation. Both normal and reversed intercalary regeneration occurred in Gb'lft(RNAi) nymphs, suggesting that Gb'Lft is involved in blastema cell proliferation and longitudinal leg regeneration under the Ds/Ft signaling pathway, but it is not required for intercalary regeneration.
Minakata Kuma, Hirata Masahiro, Yoshimasa Hamada, Seiichi Oyadomari and Naoyuki Shimomura : Investigation of Appropriate Condition for Induction of Unfolded Protein Response of Endoplasmic Reticulum in EGFP-293A Cells by Application of Nanosecond Pulsed Electric Fields, 2025 IEEE Pulsed Power & Plasma Science (PPPS), 2-pages, Berlin, Jun. 2025.
2.
Masahiro Hirata, Shogo Tanioka, Yoshimasa Hamada, Seiichi Oyadomari and Naoyuki Shimomura : Study on Selection of Appropriate Conditions of Nanosecond Pulsed Electric Field for Activation of Unfolded Protein Response Using GFP-Expressing Cells, 2024 IEEE International Power Modulator and High Voltage Conference IPMHVC 2024, Indianapolis, May 2025.
(Keyword)
endoplasmic reticulum / GFP / nsPEF / pulse electric fields / unfolded protein response
Kuma Minakata, Masahiro Hirata, Yoshimasa Hamada, Seiichi Oyadomari and Naoyuki Shimomura : Investigation of Appropriate Condition for Induction of Unfolded Protein Response of Endoplasmic Reticulum in EGFP-293A Cells by Application of Nanosecond Pulsed Electric Fields, IEEE International Pulsed Power Conference, Jan. 2025.
Hirata Masahiro, Tanioka Shogo, Yoshimasa Hamada, Seiichi Oyadomari and Naoyuki Shimomura : Study of Appropriate Condition of Nanosecond Pulsed Electric Fields for Induction of Unfolded Protein Response Using GFP-Expressing Cell, The 2023 IEEE Pulsed Power and Plasma Science Conference, 5-pages, San Antonio, Jun. 2023.
Akira Izutani, Yuji Furumoto, Yoshimasa Hamada, Masato Miyake, Kenji Teranishi, Naoyuki Shimomura and Seiichi Oyadomari : The Influence of Applying High Electrical Field Pulses on Unfolded Protein Response of cells, The 2019 IEEE Pulsed Power and Plasma Science Conference, 4-pages, Orlando, Jun. 2019.
Yuji Furumoto, Daiki Sato, Kenji Teranishi, Naoyuki Shimomura, Yoshimasa Hamada, Masato Miyake and Seiichi Oyadomari : Activation of Endoplasmic Reticulum Stress Response by Applying of Nanosecond Pulsed Electric Fields for Medical Application, 2018 IEEE International Power Modulator and High Voltage Conference Ipmhvc 2018, 456-460, Jun. 2018.