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Life Sciences

 

Development of antimetastatic drugs targeting cancer-associated sugar chains

OHTSUBO Kazuaki, Faculty of Life Sciences
 
The sialyl-Tn antigen is a glycan tumor marker molecule that facilitates tumor invasion and metastasis. Its presence is associated with a poor prognosis for cancer patients. Using chemical screening, we have obtained chemical compounds bearing an ST6GalNAc-I inhibitory activity, thereby suppressing the sialyl-Tn antigen-induced tumor invasion. We are working on developing antimetastatic drugs by focusing on molecular modifications of ST6GalNAc-I inhibitor compounds for structural optimization, based on X-ray crystallography of the enzyme-compound complexes. Next generation drugs targeting cancer-associated glycans must provide a new concept for drug discovery, and must contribute to improved outcomes for current multimodal cancer treatments and quality of life for patients.
 
 

Impact of Asian dust and PM2.5 in patients with acute myocardial infarction / out-of-hospital cardia arrest and identification of susceptible group

KOJIMA Sunao, Faculty of Life Sciences

Epidemiological studies have demonstrated the potential association of Asian dust and PM2.5 with adverse health effects. Asian dust contains harmful chemical agents such as sulphur and nitrogen oxides, by-products formed from combusted coal and other fossil fuels, and microbiological materials that have been suggested as causing an increase in the incidence of respiratory events caused by inflammation. Particular air pollutants may enhance atherothrombotic processes via the generation of pulmonary inflammation or by direct translocation into systemic circulation, where smaller particles may increase the risk of cardiovascular disease. We planned a project to elucidate the association between air pollutants and the incidence of AMI and OHCA during a definite period in a population of patients from a well-defined geographical region known to have greater than average susceptibility to AMI and OHCA.
 
 

Development of novel antibiotics targeting bacterial amino acid synthase and their application to clinical use

SAWA Tomohiro, Faculty of Life Sciences

This research project is aimed at discovering novel antibiotics that target the inhibition of specific bacterial amino acid synthase. The antibiotics will be examined to determine their therapeutic efficacy in fighting life-threating bacterial infections, and particularly drug resistant bacteria. The antibiotics will also be examined to see whether they can enhance the chemotherapeutic potential of existing drugs. The current study is being conducted to establish a novel chemotherapeutic approach to controlling infectious diseases caused by emerging, re-emerging, and drug resistant bacteria.
 
 

Does periodontal infection increase nursing care in Alzheimer's disease?

HASEGAWA Yu, Faculty of Life Sciences

Inflammatory responses brought on by periodontal disease (PD) are known to induce cardiovascular injuries, including stroke. Recent evidence suggests that PD correlates with the pathogenesis of Alzheimer’s disease (AD), though it is unclear how PD-induced brain inflammation modifies cognitive impairment and systemic organ dysfunction in AD patients. This project is aimed at clarifying whether brain inflammation caused by PD is significant in AD prognosis and the burden of care. To pursue these answers, we employ AD model mice, which undergo intracerebroventricular injection of lipopolysaccharides derived from PD, and evaluate the cognitive function and extracerebral organ injuries, especially sarcopenia.
 
 

Culture systems for expansion of hematopoietic stem and progenitor cells

HASEGAWA Yu, Faculty of Life Sciences

Inflammatory responses brought on by periodontal disease (PD) are known to induce cardiovascular injuries, including stroke. Recent evidence suggests that PD correlates with the pathogenesis of Alzheimer’s disease (AD), though it is unclear how PD-induced brain inflammation modifies cognitive impairment and systemic organ dysfunction in AD patients. This project is aimed at clarifying whether brain inflammation caused by PD is significant in AD prognosis and the burden of care. To pursue these answers, we employ AD model mice, which undergo intracerebroventricular injection of lipopolysaccharides derived from PD, and evaluate the cognitive function and extracerebral organ injuries, especially sarcopenia.
 
 

Culture systems for expansion of hematopoietic stem and progenitor cells

MASUDA Takeshi, Faculty of Life Sciences

Hematopoietic stem cells (HSC) demonstrate both self-renewal and differentiation abilities. Currently, an HSC transplant is the only therapy available for the treatment of hematologic cancer and hemoglobinopathies. However, approximately 40% of all patients cannot receive this therapy because of human leukocyte antigen compatibility issues and treatment costs. If HSCs were expandable, many more patients would have the chance to receive HSC transplants. Yet, there is no gold standard culture system for immature HSCs. In this project, the applicant intends to develop an in vivo mimic culture system for immature HSCs, and will unveil the regulating mechanisms of HSC self-renewal by using original proteomic techniques.
 


Role of ROR1 in cell membrane organization and dynamics in cancer

YAMAGUCHI Tomoya, Priority Organization for Innovation and Excellence / Faculty of Life Sciences

We previously identified the receptor tyrosine kinase-like orphan receptor 1 (ROR1) as a target for transcriptional activation via the lineage-survival oncogene TTF-1 in lung adenocarcinoma. ROR1 facilitates the interaction of CAVIN1 and CAV1 at the plasma membrane in a kinase activity-independent manner, which in turn sustains caveolae formation and pro-survival signaling towards AKT through multiple RTKs such as EGFR, MET and IGF-IR, via its scaffold function for CAVIN1 and CAV1 in lung cancer. In this project, we focus on the role of ROR1 as a caveolae-regulating molecule for cell membrane organization and dynamics in cancer. The goal of this project is to understand the molecular pathogenesis of human solid tumor, hard-to-cure cancers, especially lung cancer, and then to translate our findings in order to develop novel strategies for better diagnosis, treatment and prevention.
 


R&D of myelin quantification for detecting preclinical neurodegenerative disorders on clinical MRI

YONEDA Tetsuya, Faculty of Life Sciences

Myelin, found in white matter in the brain, plays an important role in neuronal activity and signal transmission. The aim of this research is to develop a high-accuracy quantification protocol using magnetic resonance imaging (MRI). We use the phase of the MRI signal to quantitate myelin because it is known to be a physical variable sensitive to the magnetic susceptibility of biological tissue. Phase information of white matter simultaneously contains various elements, including myelin. Our research factorizes them to drive the myelin fraction in the phase. We expect our research to be utilized in the image diagnosis of various neurodegenerative disorders, such as Parkinson’s disease, in which the myelin fraction of white matter is causally decreased.
 


Mechanisms of cerebral cortex expansion in primates

HATAKEYAMA Jun, Institute of Molecular Embryology and Genetics

Expansion of the cerebral cortex is one of the main factors related to advanced cognitive and sensorimotor skills. Primates, including human beings, have a particularly expanded cerebral cortex. However, it is still unclear how species-specific cerebral cortex size is determined and what mechanisms underlie the massive enlargement of the human cerebral cortex. I aim to elucidate the regulation mechanism that controls brain size in various mammalian species, including primates and rodents, to gain insights into cerebral cortex expansion.

 


Development of novel technology for fabricating scaffold-free functional vascular tissue

NOGUCHI Ryo, University Hospital

The aim of this project is to develop a unique technology that can provide completely scaffold-free, cell-based, three-dimensional vascular graft engineering utilizing the phenomenon of cell aggregation (spheroid formation) and self-assembling tissue spheroids. In our developing system, vascular component cells such as endothelial cells, smooth muscle cells and fibroblasts are fused to form a vascular tissue spheroid. Next, we managed to form three-dimensional vascular tissue using a simple tissue engineering process. Finally, we elucidated tissue to fabricate cell-based scaffold-free vascular tissue. Aiming at applications in clinical vascular surgery, further development is ongoing in our laboratory.
 
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