研究者データベース

山崎 淳平(ヤマザキ ジユンペイ)
獣医学研究院 附属動物病院
特任准教授

基本情報

所属

  • 獣医学研究院 附属動物病院

職名

  • 特任准教授

学位

  • 博士(獣医学)(東京大学)

論文上での記載著者名

  • Jumpei Yamazaki

ホームページURL

科研費研究者番号

  • 20732902

J-Global ID

研究分野

  • ライフサイエンス / 獣医学 / 臨床獣医学
  • ライフサイエンス / 獣医学 / 臨床獣医学
  • ライフサイエンス / 獣医学 / 臨床獣医学

職歴

  • 2019年05月 - 現在 北海道大学 大学院獣医学研究院 附属動物病院 特任准教授
  • 2015年08月 - 2019年05月 北海道大学 (連合)獣医学研究科 助教
  • 2013年12月 - 2015年07月 北海道大学 (連合)獣医学研究科 特任助教
  • 2012年11月 - 2013年11月 Temple University Fels Institute for Cancer Research and Molecular Biology Associate Scientist
  • 2011年11月 - 2012年10月 Temple University Fels Institute for Cancer Research and Molecular Biology Postdoctoral Fellow
  • 2008年04月 - 2011年10月 The University of Texas, MD Anderson Cancer Center Department of Leukemia Postdoctoral Fellow
  • 2007年04月 - 2008年03月 国立感染症研究所 血液・安全性研究部 協力研究員

学歴

  • 2004年04月 - 2008年03月   東京大学   農学生命科学研究科
  • 1998年04月 - 2004年03月   日本大学   生物資源科学部   獣医学科

所属学協会

  • 日本エピジェネティクス研究会   日本獣医学会   

研究活動情報

論文

  • Hiroshi Ohta, Jumpei Yamazaki, Jaroslav Jelinek, Teita Ishizaki, Yumiko Kagawa, Nozomu Yokoyama, Noriyuki Nagata, Noboru Sasaki, Mitsuyoshi Takiguchi
    The Journal of veterinary medical science 82 5 632 - 638 2020年05月20日 [査読有り][通常論文]
     
    DNA methylation is the covalent modification of methyl groups to DNA mostly at CpG dinucleotides and one of the most studied epigenetic mechanisms that leads to gene expression variability without affecting the DNA sequence. Genome-wide analysis of DNA methylation identified the signatures that could define subtypes of human lymphoma patients. The objective of this study was to conduct the genome-wide analysis of DNA methylation in dogs with gastrointestinal lymphoma (GIL). Genomic DNA was extracted from endoscopic biopsies from 10 dogs with GIL. We performed Digital Restriction Enzyme Assay of DNA Methylation (DREAM) for genome-wide DNA methylation analysis that could provide highly quantitative information on DNA methylation levels of CpG sites across the dog genome. We successfully obtained data of quantitative DNA methylation level for 148,601-162,364 CpG sites per GIL sample. Next, we analyzed 83,132 CpG sites to dissect the differences in DNA methylation between GIL and normal peripheral blood mononuclear cells (PBMCs). We found 383-3,054 CpG sites that were hypermethylated in GIL cases compared to PBMCs. Interestingly, 773 CpG sites including promoter regions of 61 genes were identified to be commonly hypermethylated in more than half of the cases, suggesting conserved DNA methylation patterns that are abnormal in GIL. This study revealed that there was a large number of hypermethylated sites that are common in most of canine GIL. These abnormal DNA methylation could be involved in tumorigenesis of the canine GIL.
  • Teita Ishizaki, Jumpei Yamazaki, Shinji Meagawa, Nozomu Yokoyama, Keisuke Aoshima, Mitsuyoshi Takiguchi, Takashi Kimura
    Veterinary and comparative oncology 2020年03月18日 [査読有り][通常論文]
     
    Canine malignant melanoma is a common cancer with a high mortality rate and is a clinically important disease. DNA methylation has been considered to be a potential tumorigenic mechanism through aberrant DNA methylation at promoter region which represses gene transcription. Global hypomethylation could also facilitate chromosome instability. There are few reports regarding DNA methylation in canine malignant melanoma; therefore, the purpose of this study was to examine DNA methylation status of long interspersed nucleotide element-1 (LINE-1) to be a surrogate marker of genome-wide methylation changes in this disease. We measured levels of DNA methylation of two adjacent cytosine-guanine sites on CpG island (CGI) at the putative promoter of canine LINE-1 sequence by bisulphite-pyrosequencing in 41 canine melanoma patient samples as well as six cell lines compared with normal mucosae. The survival rates were obtained from owners or medical records. We found DNA methylation levels of LINE-1 in normal mucosae were methylated. Interestingly, both melanoma cell lines and clinical melanoma samples showed remarkable hypomethylation. In addition, patients with lower LINE-1 methylation showed worse prognosis than those with higher LINE-1 methylation, though the difference did not reach statistical significance (P = .09). Here, we demonstrate that hypomethylation of LINE-1 is an epigenetically aberrant feature in canine melanoma with possible prognostic value.
  • J. Yamazaki, J. Jelinek, S. Hisamoto, A. Tsukamoto, M. Inaba
    Veterinary Journal 231 48 - 54 2018年01月01日 [査読有り][通常論文]
     
    DNA methylation is the conversion of cytosine to 5-methylcytosine, leading to changes in the interactions between DNA and proteins. Methylation of cytosine-guanine (CpG) islands (CGIs) is associated with gene expression silencing of the involved promoter. Although studies focussing on global changes or a few single loci in DNA methylation have been performed in dogs with certain diseases, genome-wide analysis of DNA methylation is required to prospectively identify specific regions with DNA methylation change. The hypothesis of this study was that next-generation sequencing with methylation-specific signatures created by sequential digestion of genomic DNA with SmaI and XmaI enzymes can provide quantitative information on methylation levels. Using blood from healthy dogs and cells obtained from canine lymphoma cell lines, approximately 100,000 CpG sites across the dog genome were analysed with the novel method established in this study. CpG sites in CGIs broadly were shown to be either methylated or unmethylated in normal blood, while CpG sites not within CpG islands (NCGIs) were largely methylated. Thousands of CpG sites in lymphoma cell lines were found to gain methylation at normally unmethylated CGI sites and lose methylation at normally methylated NCGI sites. These hypermethylated CpG sites are located at promoter regions of hundreds of genes, such as TWIST2 and TLX3. In addition, genes annotated with ‘Homeobox’ and ‘DNA-binding’ characteristics have hypermethylated CpG sites in their promoter CGIs. Genome-wide quantitative DNA methylation analysis is a sensitive method that is likely to be suitable for studies of DNA methylation changes in cancer, as well as other common diseases in dogs.
  • A. D. Kelly, H. Kroeger, J. Yamazaki, R. Taby, F. Neumann, S. Yu, J. T. Lee, B. Patel, Y. Li, R. He, S. Liang, Y. Lu, M. Cesaroni, S. A. Pierce, S. M. Kornblau, C. E. Bueso-Ramos, F. Ravandi, H. M. Kantarjian, J. Jelinek, J-P J. Issa
    LEUKEMIA 31 10 2011 - 2019 2017年10月 [査読有り][通常論文]
     
    Genetic changes are infrequent in acute myeloid leukemia (AML) compared with other malignancies and often involve epigenetic regulators, suggesting that an altered epigenome may underlie AML biology and outcomes. In 96 AML cases including 65 pilot samples selected for cured/not-cured, we found higher CpG island (CGI) promoter methylation in cured patients. Expanded genome-wide digital restriction enzyme analysis of methylation data revealed a CGI methylator phenotype independent of IDH1/2 mutations we term AML-CGI methylator phenotype (CIMP) (A-CIMP+). A-CIMP was associated with longer overall survival (OS) in this data set (median OS, years: A-CIMP+ = not reached, CIMP- = 1.17; P = 0.08). For validation we used 194 samples from The Cancer Genome Atlas interrogated with Illumina 450k methylation arrays where we confirmed longer OS in A-CIMP (median OS, years: A-CIMP+ = 2.34, A-CIMP- = 1.00; P = 0.01). Hypermethylation in A-CIMP+ favored CGIs (OR: CGI/non-CGI = 5.21), and while A-CIMP+ was enriched in CEBPA (P = 0.002) and WT1 mutations (P = 0.02), 70% of cases lacked either mutation. Hypermethylated genes in A-CIMP+ function in pluripotency maintenance, and a gene expression signature of A-CIMP was associated with outcomes in multiple data sets. We conclude that CIMP in AML cannot be explained solely by gene mutations (for example, IDH1/2, TET2), and that curability in A-CIMP+ AML should be validated prospectively.
  • Tomomitsu Tahara, Jumpei Yamazaki, Sayumi Tahara, Masaaki Okubo, Tomohiko Kawamura, Noriyuki Horiguchi, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Tomoyuki Shibata, Makoto Kuroda, Naoki Ohmiya
    SCIENTIFIC REPORTS 7 1 3090  2017年06月 [査読有り][通常論文]
     
    DNA methylation is associated with "field defect" in the gastric mucosa. To characterize "field defect" morphologically, we examined DNA methylation of non-neoplastic gastric mucosa in relation to their morphology seen by narrow-band imaging (NBI) with magnifying endoscopy. Magnifying NBI of non-neoplastic gastric body was classified as follows: normal-small and round pits with uniform subepithelial capillary networks; type 1-a little enlarged round pits with indistinct subepithelial capillary networks; type 2-remarkably enlarged pits with irregular vessels; and type 3-clearly demarcated oval or tubulovillous pits with bulky coiled or wavy vessels. Methylation of nine candidate genes (MYOD1, SLC16A12, GDNF, IGF2, MIR 124A1, CDH1, PRDM5, RORA and MLF1) were determined by bisulfite pyrosequencing. Infinium HumanMethylation450 array was used to characterize the methylation of >450,000 CpG sites. Mean Z score methylation of nine genes positively correlated with the changes of mucosal patterns from normal to types 1, 2, and 3 (P < 0.0001). Genome-wide analysis showed that development of mucosal patterns correlated with methylation accumulation especially at CpG islands. Genes with promoter CpG islands that were gradually methylated with the development of mucosal patterns significantly enriched the genes involved in zinc-related pathways. The results indicates that gastric mucosal morphology predicts a "field defect" in this tissue type. Accumulation of DNA methylation is associated with "field defect" in the non-neoplastic gastric mucosa. Endoscopic identification of "field defect" has important implications for preventing gastric cancer. Our results suggest that magnifying NBI of gastric mucosal morphology predicts a "field defect" in the gastric mucosa.
  • N. Yokoyama, H. Ohta, J. Yamazaki, Y. Kagawa, O. Ichii, N. Khoirun, T. Morita, T. Osuga, S. Y. Lim, N. Sasaki, K. Morishita, K. Nakamura, M. Takiguchi
    JOURNAL OF COMPARATIVE PATHOLOGY 156 2-3 183 - 190 2017年02月 [査読有り][通常論文]
     
    Inflammatory colorectal polyps (ICRPs) are characterized by the formation of multiple or solitary polyps with marked neutrophil infiltration in the colorectal area, and are speculated to be a novel form of breed-specific canine idiopathic inflammatory bowel disease (IBD). In human IBD, toll-like receptor (TLR) 2 and TLR4 have been reported to be involved in the pathogenesis of the disease. The aim of this study was to evaluate the expression of TLR2 and TLR4 mRNA in the colorectal mucosa of dogs with ICRPs by in-situ hybridization using an RNAscope assay. Samples of inflamed colorectal mucosa (n = 5) and non-inflamed mucosa (n = 5) from miniature dachshunds (MDs) with ICRPs and colonic mucosa from healthy beagles (n = 5) were examined. TLR2 and TLR4 hybridization signals were localized to the colorectal epithelium, inflammatory cells and fibroblasts in the inflamed colorectal mucosa of affected dogs. The signals were significantly greater in inflamed colorectal epithelium compared with non-inflamed epithelium of MDs with ICRPs and healthy beagles (P <0.05). These results suggest that increased expression of TLR2 and TLR4 mRNA in the inflamed colorectal mucosa results from not only inflammatory cell infiltration, but also the upregulation of TLR2 and TLR4 mRNA in the colonic epithelium. (C) 2016 Elsevier Ltd. All rights reserved.
  • Akiyoshi Tani, Jumpei Yamazaki, Kensuke Nakamura, Mitsuyoshi Takiguchi, Mutsumi Inaba
    Japanese Journal of Veterinary Research 65 4 201 - 206 2017年 [査読有り][通常論文]
     
    A one-year-old castrated male mixed-breed cat was referred for detailed examination of long-term pale mucous membrane without any clinical episodes that may cause cyanosis. While no causative abnormalities were detected in thoracic radiography and echocardiography, and arterial partial pressure of oxygen was within normal value, methemoglobin concentration of the cat was increased to 30% and cytochrome b5 reductase activity, which converts methemoglobin to hemoglobin, was reduced to 2.0 IU/gHb (13.4 ± 1.7 IU/gHb in control cats, n = 3), indicating congenital methemoglobinemia. Sequence analysis of CYB5R3, which codes cytochrome b5 reductase, showed two missense mutations found in the patient, one of which was predicted to affect protein function.
  • Masahiko Sato, Jumpei Yamazaki, Yuko Goto-Koshino, Asuka Setoguchi, Masashi Takahashi, Kenji Baba, Yasuhito Fujino, Koichi Ohno, Hajime Tsujimoto
    VETERINARY JOURNAL 215 38 - 42 2016年09月 [査読有り][通常論文]
     
    Lymphoma is the most common haematopoietic malignancy in dogs. Since a high proportion of dogs with lymphoma achieve remission soon after initiation of chemotherapy, an objective marker assessing treatment efficacy is required. Following clinical remission, the residual population of tumour cells can be referred to as the minimal residual disease (MRD). MRD traditionally has been detected by cytology and flow cytometry; however, if the burden of malignant cells is low, these methods might not be sufficiently sensitive to detect MRD. As an extension of the development of PCR for antigen receptor gene rearrangements (PARR) in dogs, there has been recent progress in the application of real-time quantitative PCR (RT-qPCR) to canine lymphoma. With the RT-qPCR system, a very high sensitivity (1 cell per 10,000 cells) has been achieved by preparing allele-specific oligonucleotide primers and probes designed from neoplastic clones of each dog. A series of MRD diagnostics studies employing the RT-qPCR system, has revealed its usefulness as a prognostic indicator, an objective marker of treatment efficacy and a predictor of relapse for dogs with lymphoma receiving chemotherapy. Introduction of the MRD monitoring system will provide an innovative scientific tool in the development of superior treatments and monitoring strategies for canine lymphoma. (C) 2016 Elsevier Ltd. All rights reserved.
  • Tomomitsu Tahara, Tomoyuki Shibata, Yasuyuki Okamoto, Jumpei Yamazaki, Tomohiko Kawamura, Noriyuki Horiguchi, Masaaki Okubo, Naoko Nakano, Takamitsu Ishizuka, Mitsuo Nagasaka, Yoshihito Nakagawa, Naoki Ohmiya
    ONCOTARGET 7 27 42252 - 42260 2016年07月 [査読有り][通常論文]
     
    Background and aim: TP53 gene is frequently mutated in gastric cancer (GC), but the relationship with clinicopathological features and prognosis is conflicting. Here, we screened TP53 mutation spectrum of 214 GC patients in relation to their clinicopathological features and prognosis. Results: TP53 nonsilent mutations were detected in 80 cases (37.4%), being frequently occurred as C:G to T:A single nucleotide transitions at 5'-CpG-3' sites. TP53 mutations occurred more frequently in differentiated histologic type than in undifferentiated type in the early stage (48.6% vs. 7%, P=0.0006), while the mutations correlated with venous invasion among advanced stage (47.7% vs. 20.7%, P=0.04). Subset of GC with TP53 hot spot mutations (R175, G245, R248, R273, R282) presented significantly worse overall survival and recurrence free survival compared to others (both P=0.001). Methods: Matched biopsies from GC and adjacent tissues from 214 patients were used for the experiment. All coding regions of TP53 gene (exon2 to exon11) were examined using Sanger sequencing. Conclusion: Our data suggest that GC with TP53 mutations seems to develop as differentiated histologic type and show aggressive biological behavior such as venous invasion. Moreover, our data emphasizes the importance of discriminating TP53 hot spot mutations (R175, G245, R248, R273, R282) to predict worse overall survival and recurrence free survival of GC patients.
  • Jumpei Yamazaki, Rodolphe Taby, Jaroslav Jelinek, Noel J. M. Raynal, Matteo Cesaroni, Sherry A. Pierce, Steven M. Kornblau, Carlos E. Bueso-Ramos, Farhad Ravandi, Hagop M. Kantarjian, Jean-Pierre J. Issa
    JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE 108 2 2016年02月 [査読有り][通常論文]
     
    Background: Acute myeloid leukemia (AML) is curable in a subset of cases. The DNA methylation regulator TET2 is frequently mutated in AML, and we hypothesized that studying TET2-specific differentially methylated CpGs (tet2-DMCs) improves AML classification. Methods: We used bisulfite pyrosequencing to analyze the methylation status of four tet2-DMCs (SP140, MCCC1, EHMT1, and MTSS1) in a test group of 94 consecutive patients and a validation group of 92 consecutive patients treated with cytarabine-based chemotherapy. Data were analyzed with hierarchical clustering, Cox proportional hazards regression, and Kaplan-Meier analyses. All statistical tests were two-sided. Results: In the test cohort, hierarchical clustering analysis identified low levels of tet2-DMC methylation in 31 of 94 (33%) cases, and these had markedly longer overall survival (median survival 72+ vs 14 months, P=.002). Similar results were seen in the validation cohort. tet2-DMC-low status was shown to be an independent predictor of overall survival (hazard ratio= 0.29, P=.0002). In The Cancer Genome Atlas (TCGA) dataset where DNA methylation was analyzed by a different platform, tet2-DMC-low methylation was also associated with improved outcome (median survival= 55 vs 15 months, P=.0003) and was a better predictor of survival than mutations in TET2, IDH1, or IDH2, individually or combined. Conclusions: Low levels of tet2-DMC methylation define a subgroup of AML that is highly curable and cannot be identified solely by genetic and cytogenetic analyses.
  • Gabriel G. Malouf, Tomomitsu Tahara, Valerie Paradis, Monique Fabre, Catherine Guettier, Jumpei Yamazaki, Hi Long, Yue Lu, Noel J-M Raynal, Jaroslav Jelinek, Roger Mouawad, David Khayat, Laurence Brugieres, Eric Raymond, Jean-Pierre J. Issa
    EPIGENETICS 10 9 872 - 881 2015年09月 [査読有り][通常論文]
     
    With the goal of studying epigenetic alterations in fibrolamellar hepatocellular carcinoma (FLC) and establish an associated DNA methylation signature, we analyzed LINE-1 methylation in a cohort of FLC and performed next-generation sequencing of DNA methylation in a training set of pure-FLCs and non-cirrhotic hepatocellular carcinomas (nc-HCC). DNA methylation was correlated with gene expression. Furthermore, we established and validated an epigenetic signature differentiating pure-FLC from other HCCs. LINE-1 methylation correlated with shorter recurrence-free survival and overall survival in resected pure-FLC patients. Unsupervised clustering using CG sites located in islands distinguished pure-FLC from nc-HCC. Major DNA methylation changes occurred outside promoters, mainly in gene bodies and intergenic regions located in the vicinity of liver developmental genes (i.e., SMARCA4 and RXRA). Partially methylated domains were more prone to DNA methylation changes. Furthermore, we identified several putative tumor suppressor genes (e.g., DLEU7) and oncogenes (e.g., DUSP4). While similar to 70% of identified gene promoters gaining methylation were marked by bivalent histone marks (H3K4me3/H3K27me3) in embryonic stem cells, similar to 70% of those losing methylation were marked by H3K4me3. Finally, we established a pure FLC DNA methylation signature and validated it in an independent dataset. Our analysis reveals a distinct epigenetic signature of pure FLC as compared to nc-HCC, with DNA methylation changes occurring in the vicinity of liver developmental genes. These data suggest new options for targeting FLC based on cancer epigenome aberrations.
  • Jumpei Yamazaki, Jaroslav Jelinek, Yue Lu, Matteo Cesaroni, Jozef Madzo, Frank Neumann, Rong He, Rodolphe Taby, Aparna Vasanthakumar, Trisha Macrae, Kelly R. Ostler, Hagop M. Kantarjian, Shoudan Liang, Marcos R. Estecio, Lucy A. Godley, Jean-Pierre J. Issa
    CANCER RESEARCH 75 14 2833 - 2843 2015年07月 [査読有り][通常論文]
     
    TET2 enzymatically converts 5-methylcytosine to 5-hydroxymethylcytosine as well as other covalently modified cytosines and its mutations are common in myeloid leukemia. However, the exact mechanism and the extent to which TET2 mutations affect DNA methylation remain in question. Here, we report on DNA methylomes in TET2 wild-type (TET2-WT) and mutant (TET2-MT) cases of chronic myelomonocytic leukemia (CMML). We analyzed 85,134 CpG sites [28,114 sites in CpG islands (CGI) and 57,020 in non-CpG islands (NCGI)]. TET2 mutations do not explain genome-wide differences in DNA methylation in CMML, and we found few and inconsistent differences at CGIs between TET2-WT and TET2-MT cases. In contrast, we identified 409 (0.71%) TET2-specific differentially methylated CpGs (tet2-DMCs) in NCGIs, 86% of which were hypermethylated in TET2-MT cases, suggesting a strikingly different biology of the effects of TET2 mutations at CGIs and NCGIs. DNA methylation of tet2-DMCs at promoters and nonpromoters repressed gene expression. Tet2-DMCs showed significant enrichment at hematopoietic-specific enhancers marked by H3K4me1 and at binding sites for the transcription factor p300. Tet2-DMCs showed significantly lower 5-hydroxymethylcytosine in TET2-MT cases. We conclude that leukemia-associated TET2 mutations affect DNA methylation at NCGI regions containing hematopoietic-specific enhancers and transcription factor-binding sites. (C)2015 AACR.
  • Tsukamoto A, Serizawa K, Sato R, Yamazaki J, Inomata T
    Experimental animals / Japanese Association for Laboratory Animal Science 64 1 57 - 64 2015年 [査読有り][通常論文]
  • Atsushi Tsukamoto, Mami Iimuro, Reiichiro Sato, Jumpei Yamazaki, Tomo Inomata
    Experimental Animals 64 2 139 - 145 2014年12月16日 [査読有り][通常論文]
     
    Isoflurane is a representative inhalant anesthesia used in laboratory animals. However, isoflurane mediates respiratory depression and adverse clinical reactions during induction. In the present study, we established a novel balanced anesthesia method in mice that combined isoflurane anesthesia with midazolam and butorphanol (MB). Thirty-four male C57BL/6J mice received either isoflurane alone or isoflurane with an intra-peritoneal MB premedication (3 mg/kg midazolam and 4 mg/kg butorphanol). The minimum alveolar concentration (MAC) in each group was evaluated. Induction time and adverse clinical reactions were recorded in each group. Core body temperature, heart rate, respiratory rate, and oxygen saturation (SPO2) were assessed before and for 1 h after induction. Premedication with MB achieved a significant reduction in MAC compared with isoflurane monoanesthesia (isoflurane, 1.38 ± 0.15% isoflurane with MB, 0.78 ± 0.10% P< 0.05). Induction time was significantly shortened with MB premedication, and adverse reactions such as excitement or incontinence were observed less frequently. Furthermore, isoflurane anesthesia with MB premedication caused increase of respiratory rates compared to isoflurane monoanesthesia. No significant decrease of SPO2 was observed in MBI anesthesia, while a decrease in SPO2 was apparent with isoflurane monoanesthesia (baseline, 98.3% ± 1.1 10 min after induction, 91.8 ± 6.4% P< 0.05). In conclusion, premedication with MB was effective for the mitigation of respiratory depression induced by isoflurane in mice, with rapid induction and fewer adverse clinical reactions.
  • Saori Umeki, Yasuo Ema, Ryoichi Suzuki, Masahito Kubo, Toshiharu Hayashi, Yasuhiko Okamura, Jumpei Yamazaki, Hajime Tsujimoto, Kenji Tani, Hiroko Hiraoka, Masaru Okuda, Takuya Mizuno
    JOURNAL OF VETERINARY MEDICAL SCIENCE 75 4 467 - 474 2013年04月 [査読有り][通常論文]
     
    Five novel, canine lymphoma cell lines (Ema, CLC, CLK, Nody-1 and UL-1) were established from dogs suffering from lymphoma and characterized in vitro and in vivo. All cell lines, except CLC, were characterized with T-cell phenotypes, by flow cytometric analysis and polymerase chain reaction for antigen receptor rearrangement. Cell proliferation rates and transcriptional levels of MYC, PTEN, KIT and FLT3 varied between each cell line. Intraperitoneal xenotransplantation of Ema, CLC, Nody-1 and UL-1 lymphoma cell lines into NOD/SCID mice induced ascites, intraperitoneal tumors and severe infiltration of lymphoma cells into the pancreas and mesentery. Establishment of novel canine lymphoma cell lines with different characteristics is critical for elucidating the pathophysiology of canine lymphoma and improving current therapies.
  • Masahiko Sato, Jumpei Yamzaki, Yuko Goto-Koshino, Masashi Takahashi, Yasuhito Fujino, Koichi Ohno, Hajime Tsujimoto
    Veterinary Journal 195 3 319 - 324 2013年03月 [査読有り][通常論文]
     
    The prognostic significance of minimal residual disease (MRD) in the early phases of chemotherapy was examined in 36 dogs with multicentric high-grade B-cell lymphoma. Sequences of immunoglobulin heavy chain (IgH) gene fragments from lymphoma cells were amplified and used to design allele-specific primers and probes for real-time PCR. The dogs were treated with a 6-month modified version of the University of Wisconsin-Madison chemotherapy protocol (UW-25) and evaluated for the MRD level at weeks 6 and 11 of UW-25.Of the 31 dogs that remained on the protocol at week 11, 14 were found to be MRD negative (< 10tumour cells/105 peripheral blood mononuclear cells [PBMCs]), whereas the other 17 were MRD positive (≥10tumour cells/105 PBMCs). The progression-free survival of the dogs with MRD-negative status at week 11 (median, 337days) was significantly longer than that of the MRD-positive dogs at the same time point (median, 196days) (P=0.0002). These results indicate the clinical significance of MRD as a prognostic marker in the early phase of chemotherapy. © 2012 Elsevier Ltd.
  • Jumpei Yamazaki, Jean-Pierre J. Issa
    INTERNATIONAL JOURNAL OF HEMATOLOGY 97 2 175 - 182 2013年02月 [査読有り][通常論文]
     
    The term "epigenetics" refers to clonally inherited stable variability in gene expression without underlying genetic changes. There are two well-known molecular mechanisms for epigenetic information: DNA methylation and histone modifications. Epigenetic changes have been recognized in the past decade as critical factors for physiological phenomena such as embryogenesis and the differentiation of normal cells. There is recent interest regarding the involvement of aberrant DNA methylation and histone modifications in mediating altered physiology in cancer. MDS is characterized by epigenetic changes, mutations in epigenetic regulators, and response to DNA methylation inhibitors, suggesting that epigenetic changes are unique features of MDS patients. In this article, recent progress in the understanding of MDS epigenetics and epigenetics-based therapies is reviewed.
  • Yamazaki J, Estecio MR, Lu Y, Long H, Malouf GG, Graber D, Huo Y, Ramagli L, Liang S, Kornblau SM, Jelinek J, Issa JP
    Epigenetics : official journal of the DNA Methylation Society 8 1 92 - 104 2013年01月 [査読有り][通常論文]
  • Gabriel G. Malouf, Joseph H. Taube, Yue Lu, Tapasree Roysarkar, Shoghag Panjarian, Marcos R. H. Estecio, Jaroslav Jelinek, Jumpei Yamazaki, Noel J-M Raynal, Hai Long, Tomomitsu Tahara, Agata Tinnirello, Priyanka Ramachandran, Xiu-Ying Zhang, Shoudan Liang, Sendurai A. Mani, Jean-Pierre J. Issa
    GENOME BIOLOGY 14 12 R144  2013年 [査読有り][通常論文]
     
    Background: Epithelial-mesenchymal transition (EMT) is known to impart metastasis and stemness characteristics in breast cancer. To characterize the epigenetic reprogramming following Twist1-induced EMT, we characterized the epigenetic and transcriptome landscapes using whole-genome transcriptome analysis by RNA-seq, DNA methylation by digital restriction enzyme analysis of methylation (DREAM) and histone modifications by CHIP-seq of H3K4me3 and H3K27me3 in immortalized human mammary epithelial cells relative to cells induced to undergo EMT by Twist1. Results: EMT is accompanied by focal hypermethylation and widespread global DNA hypomethylation, predominantly within transcriptionally repressed gene bodies. At the chromatin level, the number of gene promoters marked by H3K4me3 increases by more than one fifth; H3K27me3 undergoes dynamic genomic redistribution characterized by loss at half of gene promoters and overall reduction of peak size by almost half. This is paralleled by increased phosphorylation of EZH2 at serine 21. Among genes with highly altered mRNA expression, 23.1% switch between H3K4me3 and H3K27me3 marks, and those point to the master EMT targets and regulators CDH1, PDGFRa and ESRP1. Strikingly, Twist1 increases the number of bivalent genes by more than two fold. Inhibition of the H3K27 methyltransferases EZH2 and EZH1, which form part of the Polycomb repressive complex 2 (PRC2), blocks EMT and stemness properties. Conclusions: Our findings demonstrate that the EMT program requires epigenetic remodeling by the Polycomb and Trithorax complexes leading to increased cellular plasticity. This suggests that inhibiting epigenetic remodeling and thus decrease plasticity will prevent EMT, and the associated breast cancer metastasis.
  • Jumpei Yamazaki, Rodolphe Taby, Aparna Vasanthakumar, Trisha Macrae, Kelly R. Ostler, Lanlan Shen, Hagop M. Kantarjian, Marcos R. Estecio, Jaroslav Jelinek, Lucy A. Godley, Jean-Pierre J. Issa
    EPIGENETICS 7 2 201 - 207 2012年02月 [査読有り][通常論文]
     
    TET2 enzymatically converts 5-methyl-cytosine to 5-hydroxymethyl-cytosine, possibly leading to loss of DNA methylation. TET2 mutations are common in myeloid leukemia and were proposed to contribute to leukemogenesis through DNA methylation. To expand on this concept, we studied chronic myelomonocytic leukemia (CMML) samples. TET2 missense or nonsense mutations were detected in 53% (16/30) of patients. In contrast, only 1/30 patient had a mutation in IDH1 or IDH2, and none of them had a mutation in DNMT3A in the sites most frequently mutated in leukemia. Using bisulfite pyrosequencing, global methylation measured by the LINE-1 assay and DNA methylation levels of 10 promoter CpG islands frequently abnormal in myeloid leukemia were not different between TET2 mutants and wild-type CMML cases. This was also true for 9 out of 11 gene promoters reported by others as differentially methylated by TET2 mutations. We found that two non-CpG island promoters, AIM2 and SP140, were hypermethylated in patients with mutant TET2. These were the only two gene promoters (out of 14,475 genes) previously found to be hypermethylated in TET2 mutant cases. However, total 5-methyl-cytosine levels in TET2 mutant cases were significantly higher than TET2 wild-type cases (median = 14.0% and 9.8%, respectively) (p = 0.016). Thus, TET2 mutations affect global methylation in CMML but most of the changes are likely to be outside gene promoters.
  • M. Sato, J. Yamazaki, Y. Goto-Koshino, M. Takahashi, Y. Fujino, K. Ohno, H. Tsujimoto
    JOURNAL OF VETERINARY INTERNAL MEDICINE 25 2 285 - 291 2011年03月 [査読有り][通常論文]
     
    Background The cytoreductive efficacy of the individual components of multidrug chemotherapy for canine lymphoma is difficult to evaluate after complete remission. Objectives To compare the cytoreductive efficacy of vincristine (VCR), cyclophosphamide (CPA), and doxorubicin (DXR) in dogs that received a 6-month modified version of the University of Wisconsin-Madison chemotherapy protocol (UW-25). Animals Twenty-nine dogs with high-grade B-cell multicentric lymphoma. Methods Rearranged immunoglobulin heavy chain gene fragments from lymphoma cells were amplified by polymerase chain reaction (PCR) and sequenced to prepare clone-specific primers and probes for real-time PCR. The number of lymphoma cells in peripheral blood was measured from diagnosis to week 11 of UW-25. Results The number of lymphoma cells after the 1st administration of VCR, CPA, and DXR in weeks 1-4 was decreased in 29/29 (100%), 15/29 (51.7%), and 26/27 (96.3%) dogs, respectively. The cytoreductive efficacy of CPA was less than that of VCR and DXR. VCR, CPA, and DXR administered in weeks 6-9 were effective in 5/26 (19.2%), 5/20 (25.0%), and 14/19 (73.7%) dogs, respectively, indicating the sustained cytoreductive efficacy of DXR. CPA nonresponders were heavier and exhibited a shorter 1st remission than CPA responders. Conclusion and Clinical Importance When using UW-25 for treatment of canine lymphoma, CPA was found to have less cytoreductive efficacy than VCR and DXR. Real-time PCR-based quantification of tumor cells is an objective marker of the efficacy of chemotherapeutic agents.
  • M. Sato, J. Yamazaki, Y. Goto-Koshino, M. Takahashi, Y. Fujino, K. Ohno, H. Tsujimoto
    JOURNAL OF VETERINARY INTERNAL MEDICINE 25 2 292 - 296 2011年03月 [査読有り][通常論文]
     
    Background We developed previously a minimal residual disease (MRD) monitoring system in dogs with lymphoma by exploring a highly sensitive real-time PCR system. Objectives To identify the change in MRD before clinical relapse in dogs with lymphoma that achieved complete remission after chemotherapy. Animals Twenty dogs with multicentric high-grade B-cell lymphoma. Methods MRD levels in peripheral blood mononuclear cells (PBMCs) were measured by real-time PCR amplifying the rearranged immunoglobulin heavy chain gene. MRD measurement and clinical assessment were performed every 2-4 weeks for 28-601 days after completion of chemotherapy. An increase in MRD was defined as an increase by more than 0.5, calculated by log(10)[copy number of MRD per 105 PBMCs], based on the uncertainty level observed in a canine lymphoma cell line. Results During the follow-up period, 15 dogs relapsed in 28-320 days (median, 120 days) after completion of chemotherapy. An increase in MRD was detected 2 weeks or more before relapse in 14 of the 15 dogs, but an increase in MRD before relapse could not be detected in the remaining 1 dog. The time from increased MRD to clinical relapse was 0-63 days (median, 42 days). In contrast, no increase in MRD was detected in 5 dogs that did not experience clinical relapse. Conclusion and Clinical Importance An increase in MRD can be detected before clinical relapse in dogs with lymphoma. Application of early reinduction therapy based on an increase in MRD before clinical relapse may improve treatment outcome in canine lymphoma.
  • J. Yamazaki, M. Takahashi, A. Setoguchi, Y. Fujino, K. Ohno, H. Tsujimoto
    JOURNAL OF VETERINARY INTERNAL MEDICINE 24 4 897 - 903 2010年07月 [査読有り][通常論文]
     
    Background Tumor cell burden in dogs with lymphoma cannot be assessed accurately by diagnostic evaluation during clinical complete remission (CR). Recent advances in polymerase chain reaction (PCR)-based methods enabled us to quantify minimal residual disease (MRD) in canine lymphoma. Hypothesis/Objectives To quantify MRD in dogs with lymphoma treated with multidrug chemotherapy and to correlate it with remission duration after chemotherapy. Animals Seventeen dogs with lymphoma that achieved CR by multidrug chemotherapy. Methods Rearranged immunoglobulin heavy chain or T-cell receptor gamma chain gene fragments from lymphoma cells were PCR amplified and sequenced to prepare clone-specific primers and probes for real-time PCR to quantify MRD. MRD in the peripheral blood was monitored during and at the end of a 25-week multidrug chemotherapy protocol. Correlation between MRD at the end of chemotherapy and remission duration after chemotherapy was analyzed. Results MRD gradually decreased after initiation of multidrug chemotherapy, reached a nadir as low as < 0.019-1.0 cells/mu L at weeks 4-17, and remained low or slightly increased until week 25. MRD at the end of chemotherapy was negatively correlated with remission duration from the end of chemotherapy to relapse. Conclusion and Clinical Importance MRD could be an objective marker to indicate tumor cell burden in dogs with lymphoma even in clinical CR. MRD at the end of chemotherapy could be a prognostic factor to predict remission duration after chemotherapy.
  • Jumpei Yamazaki, Takuo Mizukami, Kazuya Takizawa, Madoka Kuramitsu, Haruka Momose, Atsuko Masumi, Yasushi Ami, Hideki Hasegawa, William W. Hall, Hajime Tsujimoto, Isao Hamaguchi, Kazunari Yamaguchi
    BLOOD 114 13 2709 - 2720 2009年09月 [査読有り][通常論文]
     
    Adult T-cell leukemia/lymphoma (ATL) is a malignant lymphoproliferative disorder caused by HTLV-I infection. In ATL, chemotherapeutic responses are generally poor, which has suggested the existence of chemotherapy-resistant cancer stem cells (CSCs). To identify CSC candidates in ATL, we have focused on a Tax transgenic mouse (Tax-Tg) model, which reproduces ATL-like disease both in Tax-Tg animals and also after transfer of Tax-Tg splenic lymphomatous cells (SLCs) to nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice. Using a limiting dilution transplantation, it was estimated that one CSC existed per 10(4) SLCs (0.01%). In agreement with this, we have successfully identified candidate CSCs in a side population (0.06%), which overlapped with a minor population of CD38(-)/CD71(-)/CD117(+) cells (0.03%). Whereas lymphoma did not develop after transplantation of 10(2) SLCs, 10(2) CSCs could consistently regenerate the original lymphoma. In addition, lymphoma and CSCs could also be demonstrated in the bone marrow and CD117(+) CSCs were observed in both osteoblastic and vascular niches. In the CSCs, Tax, Notch1, and Bmi1 expression was down-regulated, suggesting that the CSCs were derived from Pro-T cells or early hematopoietic progenitor cells. Taken together, our data demonstrate that CSCs certainly exist and have the potential to regenerate lymphoma in our mouse model. (Blood. 2009; 114: 2709-2720)
  • Jumpei Yamazaki, Kenji Baba, Yuko Goto-Koshino, Asuka Setoguchi-Mukai, Yasuhito Fujino, Koichi Ohno, Hajime Tsujimoto
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 126 3-4 321 - 331 2008年12月 [査読有り][通常論文]
     
    Lymphoma is the most common hematopoietic malignancy in dogs. Although a large proportion of dogs with lymphoma can achieve clinical remission by initial chemotherapy, most dogs die as a consequence of tumor relapse. We established a quantitative detection system for minimal residual disease (MRD) in canine lymphoma by using real-time polymerase chain reaction (PCR). A canine T-cell lymphoma-derived cell line, namely, UL-1, was used to examine the specificity and sensitivity of the MRD detecting system. Allele-specific oligonucleotide primers and probes were designed based on the sequence of T-cell receptor gamma chain (TCR gamma) gene fragment of UL-1 cells in conjunction with its downstream sequence, which were obtained from the dog genome database. The real-time PCR system for plasmid DNA containing the TCR gamma gene derived from UL-1 cells and the genomic DNA of UL-1 cells revealed that the system was accurate for 10-100,000 copies per reaction and its sensitivity was 1 cell per 10,000 cells. In order to monitor the kinetics of tumor cell number in canine lymphoma, we quantified the level of MRD in the peripheral blood of 7 dogs with lymphoma under chemotherapy. Since the lymphoma cells from the 7 patients were shown to be B-cell origin from the finding of clonal rearrangement of immunoglobulin heavy chain (IgH) gene, allele-specific oligonucleotide primers and probes were prepared based on the sequence of rearranged IgH gene in each case. The number of peripheral blood tumor cells measured by the real-time PCR was comparable to that estimated by conventional hematological examination in 2 cases of stage V lymphoma. MRD in the peripheral blood was detectable in all 7 cases, even in the complete remission (CR) phase. In the 7 lymphoma dogs, changes in the MRD levels of peripheral blood generally paralleled with the changes in the Volumes of lymph nodes. Molecular CR, in which the MRD level was below the detection limit, was not observed in any of these 7 patients under chemotherapy. The MRD level detected by the real-time PCR method described here would be useful for investigating the kinetics Of tumor cell growth and its regression in canine lymphoma patients. (C) 2008 Elsevier B.V. All rights reserved.
  • R Kano, C Inoiue, H Okano, J Yamazaki, T Takahashi, T Watari, M Tokuriki, A Hasegawa
    VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY 108 3-4 265 - 268 2005年12月 [査読有り][通常論文]
     
    The human CD20 antigen, a 35 kDa cell surface nonglycosylated hydrophobic phoshpoprotein is expressed consistently on almost all human B-cells, and its monoclonal antibody is used for the therapy on human B-cell lymphoma. In the present study, canine CD20 gene was cloned and sequenced, and the expression of CD20 mRNA was investigated in canine peripheral blood mononuclear cells (PBMCs), and lymph nodes from healthy dogs, and canine lymphoma cells. Using canine cDNA as a template, full-length of canine CD20 gene was sequenced by 5'-RACE and 3'-RACE methods. The full-length of the cDNA sequence of canine CD20 was 1239 bp encoding 297 amino acids. The amino acid sequences of canine CD20 showed 73 and 68% sequence similarities with those of human and mouse, respectively. Canine CD20 was predicted to contain domains of amino acid sequences consisting of two extracellular domains (EM), four transmembrane domains (TM), and three intracellular domains (IC) as in human CD20. Canine CD20 mRNA was detected in PBMCs and lymph node from healthy dogs, and B-cells of canine lymphoma, but not in T-cell lymphoma cells and non-T and non-B-cell lymphoma cells by RT-PCR analysis. From these results, canine CD20 might be targeted for monoclonal antibody therapy against B-cell lymphoma of dogs. (c) 2005 Elsevier B.V. All rights reserved.
  • J Sano, S Nagafuchi, J Yamazaki, K Oguma, R Kano, A Hasegawa
    RESEARCH IN VETERINARY SCIENCE 79 3 197 - 201 2005年12月 [査読有り][通常論文]
     
    The Bcl-2 gene is the first member of a rapidly expanding family of genes that regulate apoptosis. Bcl-2 has been shown to repress cell death triggered by a diverse array of stimuli including chemotherapy and gamma-irradiation. Chemotherapy of feline lymphoma is generally carried out with antineoplastic drugs, which are reported to induce apoptosis in tumor cells. However, the precise apoptotic signals, induced by chemotherapeutic drugs against feline tumors have not been fully characterized. Therefore, we have evaluated the expression of Bcl-2 and Bcl-xL in FT-1 upon in vitro treatment with these drugs. In the present study, full length of feline Bcl-xL gene was sequenced, and the expressions of Bcl-2 and Bcl-xL mRNAs in feline lymphoma cell line (FT-1) cultured with doxorubicin, prednisolone or vincristine were investigated. Feline Bcl-xL clone was 1163 base pairs in length and encoded 233 amino acids. The predicted amino acid sequence was 99.1%, 98.7%, 96.1%, 97.4%, 97.0% and 97.9% homologous to predicted Bcl-xL of dog, human, mouse, pig, rat and sheep, respectively. The levels of Bcl-2 transcripts at 24 h incubation in FT-1 stimulated with doxorubicin (0.3 mu g/ml), prednisolone (0.2 mu g/ml) and vincristine (5 ng/ml) were increased to about 41.0-, 62.0- and 11.1-fold to those in non-stimulated FT-1, respectively. Oil the other hand, the level of Bcl-xL transcripts at 24 h incubation in FT-1 stimulated by doxorubicin and prednisolone were significantly increased about 4.2- and 5.8-folds to the controls and inducible level of Bcl-xL by vincristine was decreased about 0.35-folds. (c) 2005 Elsevier Ltd. All rights reserved.
  • N Nagashima, R Kano, A Hirai, J Yamazaki, C Inoue, M Hisasue, PF Moore, A Hasegawa
    VETERINARY RECORD 157 12 347 - 349 2005年09月 [査読有り][通常論文]
     
    A three-year-old cat with lymphadenopathy, non-regenerative anaemia and marked leucocytosis (171(.)3 x 10(9) white blood cells/l) was diagnosed with monocytic leukaemia and treated with a combination of anticancer drugs. A number of mature and immature monocyte-like cells were detected in the peripheral blood and bone marrow; they proved to be monocytic cells by cytochemical examination and an analysis of their cell surface phenotype, indicating that the cat suffered from acute myeloid leukaemia, subclassified as monocytic leukaemia (MS). Treatment with cytarabine, doxorubicin, vincristine and prednisolone greatly reduced the number of blast cells in the cat's peripheral blood and bone marrow. The cat was in partial remission for 67 days and survived for 95 days after it was first examined.
  • J Yamazaki, N Hasebe, S Nagafuchi, K Baba, H Tsujimoto, R Kano, A Hasegawa
    VETERINARY MICROBIOLOGY 101 1 1 - 8 2004年06月 [査読有り][通常論文]
     
    In the present study, full length of feline bax,. bcl-2, bcl-xL and caspase 3 genes were sequenced and the expression of, these mRNAs were also investigated in FIV-infected lymphocytes. The full length cDNA sequence of bax (646 bp), bcl-2 (1423 bp), bcl-xL (1163 bp) and caspase 3 genes (1208 bp) contained a single open reading frame of 579 bp coding 193 amino acids, 708 bp coding 236 amino acids, 702bp coding 234,amino acids and 834 bp coding 278 amino acids, respectively. Number of apoptotic Kumi-1 cells gradually increased after FIV infection and approximately 70% were apoptotic and 30% were viable in the cells infected with FIV after 8-day incubation, though approximately 80% were non-apoptotic and 20% were dead in non-infected cells. The expression of bcl-2 mRNA in lymphocytes of established cell line was increased by FIV. The amounts of mRNAs of bax, caspase 3 and bcl-xL in FIV-infected cells were not different from those in uninfected control cells. (C) 2004 Elsevier B.V. All rights reserved.

講演・口頭発表等

  • イヌ腫瘍の新たなメカニズム~異常DNAメチル化~  [招待講演]
    山崎淳平
    第16回日本獣医内科学アカデミー学術大会(JCVIM2020) 2020年02月
  • AML患者の治療奏功群を規定するTET2特異的可変メチル化領域の同定  [招待講演]
    山崎淳平
    第42回日本分子生物学会年会 2019年12月
  • イヌを用いたトランスレーショナル・エピジェネティクス研究  [招待講演]
    山崎淳平
    日本人類遺伝学会第64回大会 2019年11月
  • エピジェネティクス 臨床応用の新たな可能性  [招待講演]
    山崎 淳平
    第14回日本獣医内科学アカデミー学術大会(JCVIM2018) 2018年02月
  • 犬のリンパ腫における微小残存病変(MRD)  [招待講演]
    山崎 淳平
    第12回日本獣医がん学会 2015年01月
  • リンパ腫の微小残存病変(MRD)定量システム  [招待講演]
    山崎 淳平
    第7回日本獣医内科学アカデミー学術大会(JCVIM2011) 2011年02月
  • リンパ腫症例における微小残存病変(MRD)定量でわかること  [招待講演]
    山崎 淳平
    第4回日本獣医内科学アカデミー学術大会(JCVIM2007) 2007年08月

その他活動・業績

受賞

  • 2017年02月 第13回 日本獣医内科学アカデミー学術大会(JCVIM 2017) 研究アワード(文永堂出版 JVM賞)
     イヌにおけるDNAメチル化ゲノムワイド解析法の樹立 
    受賞者: 久本真也;山崎淳平;稲葉睦
  • 2008年03月 日本獣医学会 第145回日本獣医学会 大会長賞
     イヌのリンパ腫における微小残存病変についての研究 
    受賞者: 山崎淳平
  • 2006年09月 The 16th European College of Veterinary Internal Medicine Oral Abstract Presentation Award
     Quantification of minimal residual disease (MRD) using real-time polymerase chain reaction in canine lymphoma. 
    受賞者: 山崎淳平

共同研究・競争的資金等の研究課題

  • DNAメチル化解析による種雄牛由来精子の新規評価法開発
    公益財団法人 高橋産業経済研究財団:研究助成
    研究期間 : 2019年 -2020年 
    代表者 : 山崎 淳平
  • イヌの新規ゲノムワイドDNAメチル化解析:腫瘍性疾患特異的DNAメチル化の同定
    文部科学省:科学研究費補助金 基盤研究(C)(一般)
    研究期間 : 2018年 -2020年 
    代表者 : 山崎 淳平
  • TET2によるエンハンサー特異的DNA脱メチル化機構の解明
    公益財団法人 住友電工グループ:社会貢献基金
    研究期間 : 2018年 -2019年 
    代表者 : 山崎 淳平
  • TET2によるエンハンサー特異的DNA脱メチル化機構の解明
    公益財団法人金原一郎記念医学医療振興財団:
    研究期間 : 2018年 -2019年 
    代表者 : 山崎 淳平
  • DNAメチル化網羅解析法による種雄牛の受胎性の評価
    公益財団法人伊藤記念財団:研究助成
    研究期間 : 2018年 -2019年 
    代表者 : 山崎 淳平
  • TET2が司るDNA脱メチル化メカニズムの解明
    公益財団法人 上原記念生命科学財団:研究奨励金
    研究期間 : 2017年 -2019年 
    代表者 : 山崎 淳平
  • DNA脱メチル化酵素TET2の結合因子同定による難治性血液疾患メカニズムの解明
    公益信託 永尾武難病研究基金:
    研究期間 : 2017年 -2018年 
    代表者 : 山崎 淳平
  • 網羅的DNAメチル化解析が同定する肥満によるエピジェネティックな変化
    クリニカルニュートリション研究会:スカラーシッププログラム
    研究期間 : 2017年 -2018年 
    代表者 : 山崎 淳平, 山下 青
  • DNAメチル化解析を用いたウシの精液性状変化の検出
    公益財団法人 北海道科学技術総合振興センター:若手研究人材育成事業
    研究期間 : 2017年 -2018年 
    代表者 : 山崎 淳平
  • DNAメチル化解析による環境中鉛汚染水の毒性メカニズム解明
    公益財団法人 クリタ水・環境科学振興財団:国内研究助成
    研究期間 : 2017年 -2018年 
    代表者 : 山崎 淳平
  • 新規DNAメチル化網羅探索法を用いた牛の精液性状の評価法開発
    公益財団法人 伊藤記念財団:研究助成
    研究期間 : 2017年 -2018年 
    代表者 : 山崎 淳平
  • DNA脱メチル化酵素TET2によるエンハンサー領域特異的制御機構の解明
    公益財団法人 武田科学振興財団:医学系研究奨励(基礎)
    研究期間 : 2016年 -2018年 
    代表者 : 山崎 淳平
  • ユビキチン非依存性タンパク質小胞体分解におけるTRIM-SUMO-11Sプロテアソーム経路の解明
    文部科学省:科学研究費補助金 基盤研究(B)(一般)
    研究期間 : 2016年 -2018年 
    代表者 : 稲葉 睦
  • 文部科学省:科学研究費補助金(若手研究(B))
    研究期間 : 2015年 -2016年 
    代表者 : 山崎 淳平
  • イヌのリンパ腫自然発症例におけるDNAメチル化のゲノムワイド解析
    北海道大学:北海道大学総長室事業推進経費(公募型)「若手研究者自立支援(A)」
    研究期間 : 2014年04月 -2015年03月 
    代表者 : 山崎淳平

大学運営

社会貢献活動

  • 運営委員
    期間 : 2020年04月01日 - 現在
    役割 : 運営参加・支援
    主催者・発行元 : 日本獣医輸血研究会
  • 輸血前検査の適応と限界
    期間 : 2018年02月28日
    役割 : 講師
    主催者・発行元 : 北海道大学 動物医療センター


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