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Molecular analysis of leukemogenesis, particularly Adult T-cell Leukemia in Japan
Japan(IFMSA-Japan) - Miyazaki University, Miyazaki
Division of Tumor and Cellular Biochemistry, Department of Medical Sciences
Kazuhiro Morishita, MD, PhD
Kazuhiro Morishita, MD, PhD
Type of Research Project
- Basic science
What is the background of the project?
Adult T-cell Leukemia (ATL) was identified as an independent clinical entity in 1977 by its unique clinical features, and the clustering of patients in Kyushu island, southwestern Japan. Thereafter, its causative agent, HTLV-I, was identified, which lead to the detailed characterization of ATL, and virological, epidemiological studies of HTLV-I associated diseases. HTLV-I was the first retrovirus that has been shown to be associated with human disease before HIV. After infection to the HTLV-1, around 5% of HTLV-1 carriers were developed to ATL after 50 years. Therefore, it is suggested that HTLV-1 carriers have been developed ATL as a consequence of additional genetic abnormalities. We have used combining strategies from GeneChip analysis, proteomics and chromosomal analysis of Spectral Karyotyping (SKY) for identifying the causative genetic abnormalities of ATL. We are studying on the molecular mechanisms of ATL leukemogenesis and the development of novel diagnosis and treatment for ATL. The specific aims of this project are to clarify the molecular events including genetic and epigenetic abnormalities, immunological alterations, and HTLV-1 gene functions, which induce leukemogenic transformation of HTLV-1-infected T-cells and to determine the molecular mechanisms of monoclonal proliferation as well as tissue invasion of ATL cells. These studies are further conducted for the development of novel biomarkers and new strategies for the prevention, treatments, and diagnosis of HTLV-1 carriers and ATLpatients. This study includes genetic engineering including plasmid construction, gene expression analysis such as Reverse transcription polymerase chain reaction (RT-PCR) and Western blot, gene transfer, cell culture, flow cytometry, confocal microscopy, and interpretation of data.
What is the aim of the project?
The specific aims of this project are to clarify the molecular events including genetic and epigenetic abnormalities, immunological alterations, and HTLV-1 gene functions, which induce leukemogenic transformation of HTLV-1- infected T-cells and to determine the molecular mechanisms of monoclonal proliferation as well as tissue invasion of ATL cells. These studies are further conducted for the development of novel biomarkers and new strategies for the prevention, treatments, and diagnosis of HTLV-1 carriers and ATL patients.
What techniques and methods are used?
This study includes genetic engineering including plasmid construction, gene expression analysis such as RT-PCR and Western blot, gene transfer, cell culture, flow cytometry, confocal microscopy, and interpretation of data.
What is the role of the student?
- The student will observe the practical experiments but will be highly involved in the analysis of the results
What are the tasks expected to be accomplished by the student?
The task for the student might be changed year to year; however, we would work together to determine expression of the related genes for leukemogenesis by RT-PCR or real-time PCR, to determine protein expression pattern by Western blot analysis, to find the function of the genes by using cultured leukemia cells, which were introduced of expression or knockdown-constructed vector of the genes. Moreover, we used flowcytometry and cell sorter for determining the phenotype of the cells and for separating the specific population of the cells. In some cases, we used mass spectrometry for determining the protein-protein interaction, and used DNA microarray analysis for determining whole expression of mRNA in the leukemia cells.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
The student(s) will receive lecture on not only the backgroud of the study but also the theoretical basis of the methods. Also, the student(s) will be invited to join a seminar in our laboratory.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- The student will have the opportunity to present the results together with the supervisor at a conference
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
No special knowledge is needed, but students who are interested in the research field are highly recommended.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students - Graduated students (less than 6 months) - Pre-Medical students from the American-British system - Students in biomedical fields - Dental medicine students (IADS members)
- Nakahata S; Ichikawa T; Maneesaay P; Saito Y; Nagai K; Tamura T; Manachai N; Yamakawa N; Hamasaki M; Kitabayashi I; Arai Y; Kanai Y; Taki T; Abe T; Kiyonari H; Shimoda K; Ohshima K; Horii A; Shima H; Taniwaki M; Yamaguchi R; Morishita K. Loss of NDRG2 expression activates PI3K-AKT signalling via PTEN phosphorylation in ATLL and other cancers. Nat Commun. 2014 Feb 26;5:3393. doi: 10.1038/ncomms4393. PubMed PMID: 24569712; PubMed Central PMCID: PMC3948061.
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