Research

NASH (Non-alcoholic steatohepatitis)

Non-alcoholic fatty liver disease (NAFLD) has become one of the most common metabolic liver diseases worldwide with an estimated prevalence ranging from 25% to 45% in Asian as well as western countries. NAFLD is defined as accumulation of lipids, mainly triglycerides, in ≥5% of hepatocytes with no evidence of excessive alcohol consumption or other secondary causes. The spectrum of NAFLD ranges from simple steatosis, a non-progressive disease entity with absence of hepatic inflammation and fibrosis, to non-alcoholic steatohepatitis (NASH), the most progressive and severe condition which can develop into cirrhosis, hepatocellular carcinoma and liver-related mortality.

The absence of an effective pharmacological therapy for NASH is a major interest for research into novel therapeutic approaches for this condition. The current targets for NASH therapeutics include the modulation of nuclear transcription factors; agents that target lipogenesis, lipotoxicity, cell death and oxidative stress; and the modulation of cellular energy homeostasis, metabolism and the inflammatory or fibrotic pathways. Novel therapeutic agents are being developed in each of these pathways, and several have shown promise in early phase trials but not been approved by FDA yet due to the failure in phase 3 trials.

Our team tries to elucidate a pathophysiologic mechanism of NASH and to develop novel therapeutic strategies for NASH.

A Role of Senescence in Metabolic Diseases

Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including diabetes, cardiovascular disorders, cancers, and neurodegenerative diseases. To date, nine tentative hallmarks that represent common denominators of mammalian aging were proposed. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication.

Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly.

Therefore, the accurate detection of senescent cells, especially in vivo, is essential and targeting senescent cells has emerged as an attractive therapeutic strategy to simultaneously treat several diseases, thereby reducing polypharmacy and the attendant risks of adverse events and drug interactions. However, a detailed role of cellular senescence in the mechanism of metabolic diseases has not been fully elucidated.

Our team tries to decipher complicated relationships between senescence and metabolic diseases (NASH and diabetes, etc) and their mechanisms that can lead to identify promising therapeutic candidates.

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