Laboratory

In this laboratory, we aim to systematically understand various chemical reactions occurring in living organisms. Through comprehensive research on the function and regulation of enzymes, which are biological catalysts, we are ultimately laying the groundwork for explaining life phenomena at the molecular level.

In particular, studies on structural characteristics, enzyme reaction mechanisms, and activity and inactivity control mechanisms are being conducted, focusing on enzymes involved in the biosynthesis of bioactive lipids. In addition, based on the understanding of enzymatic reaction kinetics, enzyme decomposition mechanism, and interaction between proteins, we would like to present an efficient approach to the treatment of related diseases.

Our lab investigates how hypoxia triggers gene expression, impacting metastasis, angiogenesis, senescence, cytoskeleton, and glycolysis. Diverse genes under hypoxia yield unique cell traits: hindered differentiation, reduced senescence, enhanced stemness, and resistance to anticancer therapy. Decades of research have unveiled these intricate mechanisms. Our research topics are followings
(1) Hypoxia, Cellular Senescence and Histone Demethylases
(2) Hypoxia, Adipogenesis, and Lipid Metabolism
(3) Inhibitors of Oxygen-Dependent Dioxygenases
(4) Signals Regulating HIF-1α and Oxygen-Dependent Dioxygenases

In our lab, we focus on elucidating the mechanisms behind how Wnt and Hippo signaling pathways are regulated to discover therapeutic targets of the diseases caused by abnormal regulation of these pathways.

Wnt and Hippo signaling pathways were first studied as factors that take part in cancer development, early development of the body, or as a mechanism regulating organ size. Nowadays, as it was also found to have connections with apoptosis, NF-κB signaling, synaptogenesis, embryonic stem cell maintenance/differentiation, as well as Alzheimer’s disease, the fields of Wnt/Hippo signaling pathway are being studied with utmost attention around the world.

We conduct experiments not only to clarify the regulatory mechanisms of Wnt and Hippo signaling pathways but also to broaden our view on involvement of these pathways to cancer development, regulation of embryonic stemness/ differentiation, and Alzheimer’s disease, using molecular biological techniques, mouse embryonic stem cells, primary neural cultures, organoids and transgenic mice etc.

As Wnt and Hippo signaling pathways have critical roles in regulating many biological phenomena, the research on these pathways have an importance as a basic study, and also provides therapeutic targets for various diseases. A lot of potential therapeutic targets have been discovered so far. However, since the targets do not have clinical significance yet, more targets should be discovered based on the studies of new biological regulatory mechanisms. To achieve our goals, our team has been conducting different projects funded by national research funds as shown below.

[1] Identification of noble signal transduction of Wnt signaling by TFEB
[2] Studying cross-talks with Wnt and Hippo signaling and providing therapeutic targets
[3] The discovery of novel components and their function in Hippo Signaling Pathway
[4] Verifying Mest/Peg1 loss-of-imprinting as a causative mechanism of Alzheimer’s disease

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In our research laboratory, we are utilizing X-ray crystallography to elucidate the three-dimensional structures of proteins.

Using this technique, we aim to comprehend the enzymatic mechanisms, ligand recognition methods of receptor proteins, and the principles underlying the interactions of signaling proteins, from both physical and chemical perspectives.

Our major research focus, we conduct structural determination and functional studies of proteins that play significant roles in the human innate immune system and bacterial proteins.

[Protein quality control in the brain during aging and neurodegeneration]
The cell biology laboratory aims to understand the maintenance and disruption of neuronal integrity, as well as the occurrence of neuronal loss during aging.
With expertise in working with mouse models and primary cells derived from them, we conduct research with the following keywords: (1) neurodegenerative diseases, (2) reactive astrogliosis, (3) ubiquitin-proteasome system, and (4) autophagy-lysosome pathway.
The primary objective of our laboratory is to develop a novel therapeutic strategy to overcome neurodegenerative diseases by regulating the cellular quality control system.
(1) Our first aim is to establish a model for enhanced neuronal viability or neuroprotection. We plan to achieve this by regulating the levels of secreted neurotoxic proteins, such as lipocalin-2 (LCN2), and by altering transcriptome profiles or modulating activation status in reactive astrocytes.
(2) Our second goal is to understand the molecular mechanisms through which glial cells, particularly astrocytes, interact with neurons and influence neuronal integrity.
(3) Lastly, we aim to apply our therapeutic strategy to animal models with neurodegenerative diseases and validate its neuroprotective effect in vivo.

[Development of New emerging technologies Bridging the Nanoscience to Bioscience]
We are pursuing to develop new emerging technologies bridging the Nanoscience to Bioscience.
In our lab, notable approaches for fabricating new types of functional nanomaterials and their versatile applications to biological sensing, imaging, and molecular delivery would be conducted.
(1) First, we aim to develop simple and robust fabrication strategies of functional nanostructures, which can be easily followed by non-expert researchers, and demonstrate their versatile applications to optical signal enhancements for early diagnosis of diseases and ubiquitous biological monitoring.
(2) Second, we aim to explore cellular behaviors from signal cellular levels to multicellular organ levels through the functional nanoprobes with high-sensitivity and high-spatial resolution for revealing the biological mechanisms.
(3) Lastly, we aim to deliver biologics (ex., drugs, genes, and etc.) in controlled and targeted manners using functional nanocarriers with biocompatibility, biodegradability, stimuli-responsivity, and target-selectivity for precision and personalized medicine.

[Unraveling the Intricate Interplay of Host-Virus Interactions]
We are pursuing to study the complex interactions between host and viruses, and their profound implications for human health and disease.

Host-virus interactions form a fascinating and complex battleground where the relationship between invading viruses and the host immune defense system shapes the outcome of infections. The interplay between a viral pathogen and its host organism involves a myriad of intricate molecular and cellular processes that govern viral entry, replication, immune evasion, and host immune activation. Understanding the underlying mechanisms driving these interactions is paramount for advancing our knowledge of virology and developing effective strategies to combat viral infections.

Our core mission rests on three fundamental pillars:

(1) Investigating the intricate roles of exosomes in viral infection and shedding light on their involvement in viral dissemination, immune regulation, and disease progression
(2) Identifying and characterizing key host factors that restrict viral replication
(3) Identifying viral strategies to manipulate host cellular system to evade immune surveillance

[Molecular mechanisms of synaptic plasticity underlying learning and memory]
A neuron communicates with neighboring neurons by releasing neurotransmitters at specialized contact sites, called synapses. Such synaptic transmission plays a major role in delivering information from one neuron to another and also integrating signals at a neuronal network level. Interestingly, the efficiency of synaptic transmission constantly changes depending on the history of neuronal activation, and in this sense, the connection strength between neurons is considered ""plastic"". This phenomenon is known as synaptic plasticity, which is widely accepted as a cellular basis of learning and memory formation in the brain. Our group aims to understand how schizophrenia risk genes, such as neurogranin, modulate synaptic plasticity and animal behaviors at the molecular level.

Our lab is focused on elucidating two fundamental principles in biology. 1. Exploring organ size control, homeostasis, and cancer development. 2. Investigating Transcription Factor Condensate Formation and Functions. Through our research efforts in these areas, we aim to advance our understanding of organ size regulation, homeostasis, transcription factor condensates, and their implications in disease development.