DSpace Collection:
http://hdl.handle.net/10203/25416
2024-03-29T08:05:54ZAnalysis of immune cell landscape in glioblastoma of CD4+ T cell-specific Atg5-deficient mice
http://hdl.handle.net/10203/309806
Title: Analysis of immune cell landscape in glioblastoma of CD4+ T cell-specific Atg5-deficient mice
Authors: Choi, Young Joon
Abstract: Autophagy is a conserved catabolic mechanism involving the lysosomal degradation of disposable or harmful cytoplasmic materials. Although the roles of autophagy in the immune system have been widely studied, the functions of autophagy in CD4+ T cells are subset- and disease-specific. Glioblastoma multiforme (GBM) is the most common and lethal form of brain tumor in adults and is often diagnosed as grade-4 tumors according to the World Health Organization classifications. Chloroquine, an autophagy inhibitor, has been used in clinical trials for GBM patients. However, the underlying mechanism of how autophagy inhibition modulates tumor-infiltrating CD4+ T cells to orchestrate antitumor immune responses against GBM remains unclear. Here, I demonstrate that CD4+ T cell-specific Atg5-deficient mice have prolonged survival in a mouse model of GBM. Furthermore, these mice have decreased numbers of tumor-infiltrating Tregs and an increased proportion of tumor-infiltrating CD4+ T cells that express high levels of IFN-gamma. The status of CD4+ T cells is critical for modulating antitumor immune responses against GBM regarding CD8+ T-cell and NK-cell responses, macrophage polarization, and antigen presentation. Collectively, my data reveal that enhancing Th1-cell responses with defective Tregs is a promising novel therapeutic intervention for GBM immunotherapy. Therefore, GBM patients could benefit from an autophagy blockade that not only targets tumor cells but also strengthens antitumor immune responses by the CD4+ T-cell modulation.
Description: 학위논문(석사) - 한국과학기술원 : 의과학대학원, 2023.2,[v, 56 p. :]2023-01-01T00:00:00ZExperimental design for evaluating adult neurogenesis-associated somatic variations in the hippocampus of Alzheimer’s disease
http://hdl.handle.net/10203/309805
Title: Experimental design for evaluating adult neurogenesis-associated somatic variations in the hippocampus of Alzheimer’s disease
Authors: Cha, Do Hyeon
Abstract: Alzheimer's disease, a neurodegenerative disease with a complex genetic architecture, is estimated to have a 60-70% heritability. Over the past decades, various germline variations associated with Alzheimer's risk have been revealed through genome-wide association studies, whole-exome and whole-genome sequencing analyses, and subsequent rare variants association studies. The various neuropathological features of Alzheimer's disease are known to appear first in the hippocampus. In particular, the mechanism by which the accumulation of neurofibrillary tangles originates in the hippocampus and transforms adjacent normal proteins into abnormal forms has been suggested. In addition, extensive evidence has been reported that cessation of adult neurogenesis occurring in the hippocampal dentate gyrus is associated with memory loss, the primary symptom of Alzheimer's disease. In this study, we performed experiments to accurately detect brain-specific somatic variations occurring in the dentate gyrus and proposed an optimal experimental design as follows. We devised the sample acquisition method via laser capture microdissection considering the embryology and anatomy of the dentate gyrus, and we optimized the whole-genome amplification method that enables amplification of extremely low amounts of DNA from the captured samples. In addition, we developed a method to measure somatic variation from whole-genome sequencing data and performed the identification of clonal somatic mutations through a probabilistic framework. This study laid the foundation for a follow-up study to efficiently prove the hypotheses of neurofibrillary tangle accumulation and adult neurogenesis impairment in the hippocampus in an integrated pipeline.
Description: 학위논문(석사) - 한국과학기술원 : 의과학대학원, 2022.8,[ii, 50 p. :]2022-01-01T00:00:00Z(The) role of growth differentiation factor 15 on adipose tissue macrophages after chronic alcohol consumption
http://hdl.handle.net/10203/295514
Title: (The) role of growth differentiation factor 15 on adipose tissue macrophages after chronic alcohol consumption
Authors: Kim, Ye Eun
Abstract: Alcohol consumption responsible for 3 million deaths each year globally and harmful use of alcohol contributes to 5.1% of the global burden of disease. Among the alcohol-induced diseases, alcoholic liver disease (ALD) is the most prevalent disease. Until now, most studies about ALD have focused on just the liver. However, it has recently been found that alcohol is also metabolized in other organs such as gut, bone marrow, and adipose tissue. Therefore, it is necessary to study ALD considering the effect of alcohol on other organs.
Adipose tissue, along with the liver, is central organ that regulates whole body metabolism. Adipose tissue and the liver are closely related, and thus, there have been many studies of organ crosstalk between the two organs especially in non-alcoholic fatty liver disease (NAFLD). However, few studies have been conducted on the effect of adipose tissue on ALD.
Thus, in this research, we demonstrate the changes of adipose tissue, especially the adipose tissue macrophages, and the role of GDF15 in those changes in chronic alcohol condition.
Description: 학위논문(석사) - 한국과학기술원 : 의과학대학원, 2021.8,[iii, 41 p. :]2021-01-01T00:00:00ZInvolvement of HCS1 helicase in Okazaki fragment processing
http://hdl.handle.net/10203/295513
Title: Involvement of HCS1 helicase in Okazaki fragment processing
Authors: Hong, Seongji
Abstract: Okazaki fragment maturation is an important process in eukaryotic DNA replication for maintaining genome integrity. The principal mechanism is processing generation of 5’-flaps which have the potential to form a variety of structure. Obviously, accumulation of unprocessed flaps is detrimental to cells, which potentially leads to mutations and chromosome aberrations that ultimately cause diseases. Dna2 and Rad27 (yeast Fen1; Flap-endonuclease 1) play central role in removing the unprocessed flaps that arise during DNA lagging strand replication process. In previous research, genetic interaction between Rad27 and HCS1 (yeast DNA helicase A; DNA polymerase α- associated helicase A), and possible involvements of HCS1 in the lagging strand synthesis were reported. We aimed to elucidate the relevance of HCS1 in flap processing with Dna2 and Rad27. We showed that the overexpression of HCS1 can suppress the lethality of Dna2 helicase mutants in Saccharomyces cerevisiae, which indicates the involvement of HCS1 in flap processing in vivo. It was also found that HCS1 strongly interacts with Rad27 and PCNA in vitro. Nuclease assay showed HCS1 stimulate the nuclease activities of Rad27 and Dna2.
Description: 학위논문(석사) - 한국과학기술원 : 의과학대학원, 2021.8,[iii, 28 p. :]2021-01-01T00:00:00Z