Oba, Junna

写真a

Affiliation

School of Medicine, Department of Extended Intelligence for Medicine, The Ishii-Ishibashi Laboratory (Shinanomachi)

Position

Assistant Professor (Non-tenured)/Research Associate (Non-tenured)/Instructor (Non-tenured)

E-mail Address

E-mail address

Related Websites

Remarks

Maiden name: Okada

Career 【 Display / hide

  • 2021.11
    -
    Present

    Keio University School of Medicine, Department of Extended Intelligence for Medicine, The Ishii-Ishibashi Laboratory, Assistant Professor

  • 2019.10
    -
    2021.10

    Keio University School of Medicine, Genomics Unit, Cancer Center, Project lecturer

  • 2018.05
    -
    2019.09

    The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Instructor

  • 2016.07
    -
    2018.04

    The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Senior Research Scientist

  • 2015.09
    -
    2016.06

    The University of Texas MD Anderson Cancer Center, Department of Melanoma Medical Oncology, Research Assistant

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Academic Background 【 Display / hide

  • 1996.04
    -
    2003.03

    Kumamoto University, School of Medicine

    Japan, University, Graduated, Other

  • 2007.04
    -
    2012.03

    Kyushu University, Graduate School of Medicine

    Japan, Graduate School, Graduated, Doctoral course

Academic Degrees 【 Display / hide

  • Medical Doctor (MD), Kumamoto University School of Medicine, Coursework, 2003.04

  • Doctor of Philosophy (PhD), Kyushu University Graduate School of Medicine, Coursework, 2012.03

Licenses and Qualifications 【 Display / hide

  • Board-Certificated Japanese Medical License, 2003.04

  • Board-Certificated Dermatology Specialist, 2009.10

 

Papers 【 Display / hide

  • The genetic and epigenetic basis of distinct melanoma types

    Oba J., Woodman S.E.

    Journal of Dermatology (Journal of Dermatology)  48 ( 7 ) 925 - 939 2021.07

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  03852407

     View Summary

    Melanoma represents the deadliest skin cancer. Recent therapeutic developments, including targeted and immune therapies have revolutionized clinical management and improved patient outcome. This progress was achieved by rigorous molecular and functional studies followed by robust clinical trials. The identification of key genomic alterations and gene expression profiles have propelled the understanding of distinct characteristics within melanoma subtypes. The aim of this review is to summarize and highlight the main genetic and epigenetic findings of melanomas and highlight their pathological and therapeutic importance.

  • Reprogramming of bivalent chromatin states in NRAS mutant melanoma suggests PRC2 inhibition as a therapeutic strategy

    Terranova C.J., Tang M., Maitituoheti M., Raman A.T., Ghosh A.K., Schulz J., Amin S.B., Orouji E., Tomczak K., Sarkar S., Oba J., Creasy C., Wu C.J., Khan S., Lazcano R., Wani K., Singh A., Barrodia P., Zhao D., Chen K., Haydu L.E., Wang W.L., Lazar A.J., Woodman S.E., Bernatchez C., Rai K.

    Cell Reports (Cell Reports)  36 ( 3 ) 109410 2021.07

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2211-1247

     View Summary

    The dynamic evolution of chromatin state patterns during metastasis, their relationship with bona fide genetic drivers, and their therapeutic vulnerabilities are not completely understood. Combinatorial chromatin state profiling of 46 melanoma samples reveals an association of NRAS mutants with bivalent histone H3 lysine 27 trimethylation (H3K27me3) and Polycomb repressive complex 2. Reprogramming of bivalent domains during metastasis occurs on master transcription factors of a mesenchymal phenotype, including ZEB1, TWIST1, and CDH1. Resolution of bivalency using pharmacological inhibition of EZH2 decreases invasive capacity of melanoma cells and markedly reduces tumor burden in vivo, specifically in NRAS mutants. Coincident with bivalent reprogramming, the increased expression of pro-metastatic and melanocyte-specific cell-identity genes is associated with exceptionally wide H3K4me3 domains, suggesting a role for this epigenetic element. Overall, we demonstrate that reprogramming of bivalent and broad domains represents key epigenetic alterations in metastatic melanoma and that EZH2 plus MEK inhibition may provide a promising therapeutic strategy for NRAS mutant melanoma patients.

  • Integrative analysis identifies four molecular and clinical subsets in uveal melanoma

    Robertson AG, Shih J, Yau C, Gibb EA, Oba J, Mungall KL, Hess JM, Uzunangelov V, Walter V, Danilova L, Lichtenberg TM, Kucherlapati M, Kimes PK, Tang M, Penson A, Babur O, Akbani R, Bristow CA, Hoadley KA, Iype L, Chang MT, Cherniack AD, Benz C, Mills GB, Verhaak RGW, Griewank KG, Felau I, Zenklusen JC, Gershenwald JE, Schoenfield L, Lazar AJ, Abdel-Rahman MH, Roman-Roman S, Stern MH, Cebulla CM, Williams MD, Jager MJ, Coupland SE, Esmaeli B, Kandoth C, Woodman SE.

    Cancer Cell 32 ( 2 ) 204 - 220 2017.08

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1535-6108

  • RT-PCR screening tests for SARS-CoV-2 with saliva samples in asymptomatic people: Strategy to maintain social and economic activities while reducing the risk of spreading the virus

    Oba J., Taniguchi H., Sato M., Takamatsu R., Morikawa S., Nakagawa T., Takaishi H., Saya H., Matsuo K., Nishihara H.

    Keio Journal of Medicine (Keio Journal of Medicine)  70 ( 2 ) 35 - 43 2021

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00229717

     View Summary

    The year 2020 will be remembered for the coronavirus disease 2019 (COVID-19) pandemic, which continues to affect the whole world. Early and accurate identification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is fundamental to combat the disease. Among the current diagnostic tests, real-time reverse transcriptase–polymerase chain reaction (RT-qPCR) is the most reliable and frequently used method. Herein, we discuss the interpretation of RT-qPCR results relative to viral infectivity. Although nasopharyngeal swab samples are often used for RT-qPCR testing, they require collection by trained medical staff. Saliva samples are emerging as an inexpensive and efficient alternative for large-scale screening. Pooled-sample testing of saliva has been applied for mass screening of SARS-CoV-2 infection. Current policies recommend isolating people with borderline cycle threshold (Ct) values (35<Ct <40), despite these Ct values indicating minimal infection risk. We propose the new concept of a “social cut-off” Ct value and risk stratification based on the correlation of Ct with infectivity. We also describe the experience of RT-qPCR screening of saliva samples at our institution. It is important to implement a scientific approach to minimize viral transmission while allowing economic and social activities to continue.

  • Elevated endogenous SDHA drives pathological metabolism in highly metastatic uveal melanoma

    Chattopadhyay C., Oba J., Roszik J., Marszalek J.R., Chen K., Qi Y., Eterovic K., Gordon Robertson A., Burks J.K., McCannel T.A., Grimm E.A., Woodman S.E.

    Investigative Ophthalmology and Visual Science (Investigative Ophthalmology and Visual Science)  60 ( 13 ) 4187 - 4195 2019.10

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  01460404

     View Summary

    PURPOSE. Metastatic uveal melanoma (UM) has a very poor prognosis and no effective therapy. Despite remarkable advances in treatment of cutaneous melanoma, UM remains recalcitrant to chemotherapy, small-molecule kinase inhibitors, and immune-based therapy. METHODS. We assessed two sets of oxidative phosphorylation (OxPhos) genes within 9858 tumors across 31 cancer types. An OxPhos inhibitor was used to characterize differential metabolic programming of highly metastatic monosomy 3 (M3) UM. Seahorse analysis and global metabolomics profiling were done to identify metabolic vulnerabilities. Analyses of UM TCGA data set were performed to determine expressions of key OxPhos effectors in M3 and non-M3 UM. We used targeted knockdown of succinate dehydrogenase A (SDHA) to determine the role of SDHA in M3 UM in conferring resistance to OxPhos inhibition. RESULTS. We identified UM to have among the highest median OxPhos levels and showed that M3 UM exhibits a distinct metabolic profile. M3 UM shows markedly low succinate levels and has highly increased levels of SDHA, the enzyme that couples the tricarboxylic acid cycle with OxPhos by oxidizing (lowering) succinate. We showed that SDHA-high M3 UM have elevated expression of key OxPhos molecules, exhibit abundant mitochondrial reserve respiratory capacity, and are resistant to OxPhos antagonism, which can be reversed by SDHA knockdown. CONCLUSIONS. Our study has identified a critical metabolic program within poor prognostic M3 UM. In addition to the heightened mitochondrial functional capacity due to elevated SDHA, M3 UM SDHA-high mediate resistance to therapy that is reversible with targeted treatment.

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • Building a versatile medical test system in a pandemic

    2021.04
    -
    2024.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 大場 純奈, Grant-in-Aid for Scientific Research (C), Principal Investigator