Researcher Database

（Last updated : 2023-08-30 13:56:02）

Visruth.jpg not found

KIMURA Tominori

Department / Course College of Pharmaceutical Sciences Department of Pharmacy

Title / Position Professor

Other Affiliations
1.	Research Organization of Open Innovation & Collaboration Research Center for Medical and Long-Term Care Management
2.	Research Organization of Science and Technology Research Center for Drug Discovery and Development Scieces

Academic background
1.	1986/12 Degree Acquisition	│ Kansai Medical University Doctor of Medical Sciences
2.	～1980/03	Department of Medicine │ Faculty of Medicine │ Kansai Medical University │ Graduated
3.	～1985/03	Doctorial Course │ Microbiology │ Graduate School, Division of Medicine │ Kansai Medical University │ Completed

Research activities
1.		The Japanese Society for Virology
2.		The Molecular Biology Society of Japan
3.		The RNA Society of Japan
4.		The Pharmaceutical Society of Japan
5.		The Japanese Society for Clinical Molecular Morphology
Display All（9）

Qualification and license
1.	2003	ICD

Subject of research
1.	Post-transcriptional regulation of gene expression: Regulatory non-coding RNA, Nucleocytoplasmic transport, Translational regulation, Post-translational regulation

Research summary
Post-transcriptional research for the eukaryotic gene expression regulation with particular emphasis on the viral pathogenesis and infection control My laboratory aims to elucidate the post-transcriptional mechanisms of eukaryotic gene expression regulation. For this purpose, my laboratory has investigated the molecular mechanisms of action of genes (Early response genes, in particular) in each stage of their expression that are responsible for regulation of both the viral pathogenesis and the host innate immune responses. 1) Research project 1: gene expression regulation by non-coding RNAs. The human genome projects have revealed that the protein-coding genes occupies only 2-3% of the 2.9 Gb-large human genome, whereas more than 90% of th genome DNA was found to be transcribed. The protein non-coding RNAs (ncRNAs) account for this discrepancy observed between the human genome and the transcriptome. The ncRNAs are believed to play a role in regulating gene expression, but the exact functional significance of non-coding RNA transcription is largely unknown, hence they are termed as the Transcripts of unknown function (TUFs). However, we recently showed that natural antisense RNA was an important modulator of interferon-alpha1 (IFN-alpha1) mRNA levels, which encodes a major effector for the host innate immunity. The IFN-alpha1 AS regulated the stabilities of IFN-alpha1 mRNA in a post-transcriptional manner, resulted in increased IFN-alpha1 protein production. This discvery not only reveals a unique regulatory pathway for controlling IFNA1 gene expression during the host innate immune response against virus infection but also provies possible candidate seed molecules for developing nucleic acid drugs that mimic the functional domain of the antisense RNA(this work has been conducted in collaboration with Professor Mikio Nishizawa, College of Life Sciences, Ritsumeikan University). 2) Research project 2: analysis of the molecular action of nuclear export elements. It has been reported that human immunodeficiency virus type 1 Rev protein works for exporting the intron-containing viral genomic RNA by acting as an adaptor for CRM1, the nuclear export receptor that indirectly targets the nuclear export element in the HIV-1 genomic RNA. We and others reported that the element, termed Rev response element, forms a conserved RNA secondary structure that Rev recognizes. This study led to the finding that IFN-alpha1 AS targets a single-stranded region within a conserved secondary structure element of the IFN-alpha1 mRNA, an element which was previously reported by us to function as the nuclearexport element of the mRNA. These findings reveal that a particular secondary structure of RNA works as the distinct targets of the cellular functions of nuclear export and stability regulations, suggesting the possibility that it enables the analysis from the new viewpoint that has not been reported so far when considering mechanisms of gene expression regulation. 3) Research project 3: Translational regulation. While investigating any cellular factors recognizing the secondary structure of IFN-alpha1 mRNA, which regulate the nuclear export, we cloned a number of candidate molecules that may also function for the translational regulation of mRNA expression. Functional dissection of the mechanisms of action of these molecules may further provide new insights of studying post-transcriptional regulation of eukaryotic gene expression system.

Present specialized field
Molecular Biology, Cell Biology, Virology, Infectious Disease Medicine (Keyword：Molecular cell biology, Virology, Microbiology, Infectious Diseases (Nosocomial infections in particular))

Books
1.	2016/12	Clinician's guide to AHCC: evidence-based nutritional immunotherapy │ ,pp.116-119 (Co-authored)
2.	2012/05	Life Science 1-From Individual To Molecule- ・3.2 Infectious Diseases │ ,pp.134-152 (Co-authored)

Papers
1.	2023/08/30	Editorial: Mechanisms of action of Natural Antisense Transcripts on the posttranscriptional regulation of sense protein coding gene expression during development and in cancer" │ Frontiers in Molecular Biosciences │ 10 (Co-authored)
2.	2021/12/15	Non-coding endogenous antisense RNAs control the expression of genes involved in innate immune responses │ ICNIM Annual Report 2021-topics │ (Sole-authored)
3.	2020/10/03	EPHA2 antisense RNA modulates EPHA2 mRNA levels in basal-like/triple-negative breast cancer cells │ Biochimie │ 179,pp.169-180 (Co-authored)
4.	2020/05	Non-coding natural antisense RNA: mechanisms of action on target gene expression regulation and its clinical implications │ YAKUGAKU ZASSHI │ ,pp.687-700 (Sole-authored)
5.	2019/06	Regulatory non-coding RNAs in nervous system development and disease │ Frontiers in Bioscience (Landmark Edition) │ 24,pp.1203-1240 (Co-authored)
Display All（22）

Academic conference presentation
1.	2018/06/28	Interferon-alpha1 antisense RNA modulates levels of interferon-alpha1 mRNA expression and antagonizes proliferation of human influenza A virus in a guinea pig model system (RNA Therapeutics Conference 2018: From Base Pairs to Bedsides)
2.	2016/12/01	Active Hexose Correlated Compound suppressed the proliferation of human breast cancer cells at least by reducing EphA2 antisense RNA, and mRNA expression levels (The 39th annual meeting of the Molecular Biology Society of Japan)
3.	2016/07/09	Effect of AHCC on metastatic mammary carcinoma-derived MDA-MB-231 cell proliferation and EphA2 gene expression that affects the tumor cell growth (The 24th annual meeting of International Congress on Nutrition and Integrative Medicine)
4.	2015/12/01	Natural antisense RNA-based oligoribonucleotide therapeutics for Influenza virus infection (日本核酸医薬学会第１回年会)
5.	2015/07/25	Effects of AHCC on regulatory roles of natural antisense RNA for human breast cancer (The 23rd International Congress on Nutrition and Integrated Medicine)
Display All（23）

Other research achievements
1.	2013/11/20	Catching the common cold (International Innovation North America November, 111-113, 2013.)
2.	2013/05/08	User Applications, Suspension cells/B-lymphoblastoid cells (Namalwa) (IBA, Solutions for Life Sciences http://www.iba-lifesciences.com/Transfection_Applications.html)
3.	2013/01/18	Featured article: stabilization of human interferon-{Alpha}1 mRNA by its antisense RNA. (Global Medical Discovery, 2013. http://globalmedicaldiscovery.com/key-scientific-articles/ stabilization-of-human-interferon-alpha1-mrna-by-its-antisense-rna/)
4.	2012/01/01	Regulatory RNA (A special issue to Frontiers in Bioscience as a managing editor; http://www.bioscience.org/special-issue-details?editor_id=193 (Frontiers in Bioscience)

Winning science prize
1.	1984/04	The British Council Scholarship (84/85 JPN/2201/268)

Acquisition patent
1.		Interferon-alpha modulater （特許第5794532号）