What is the goal of your research?

Our laboratory conducts a wide variety of research projects based on the main themes of liver, stress, and bioimaging. Although each of these core themes appears to be independent, all of them are related through research. That is to say, we systematically research liver patho-physiology (primarily, research into stress on the liver and response to the stress) through not only cellular biological and molecular biological research, but also through bioimaging techniques using light. Our main research concerns various acute and chronic stresses; however, we also look into conditions such as ischemia and reperfusion of the liver, inflammation, cell growth, death, fatty metamorphosis, fibrosis, and aging, especially from the perspective of surgical treatment. We further research a multitude of diseases and conditions that originate from stress on the liver, including cancer, metabolic syndrome, liver inflammation, liver cirrhosis, and aging.

 

What kind of research do you do? And what are your goals?

1) Various disease states and physiology related to stress on the liver (oxidant stress, injury / disability, cell proliferation / growth / death, metabolism, etc.): The liver has a strong regenerative ability and capacity for maintaining function, and is therefore considered a sophisticated mechanism. We research these control mechanisms by analyzing events that occur to the liver during injury, dysfunction, and regeneration.
Stress on the liver is caused by various external and internal factors. Stress occurs not only under special circumstances, but the burdens of daily life chronically stress the liver. As a "quiet organ," the liver is considered to be fairly tolerant to stress; however, various body failures occur due to different acute or chronic stresses on the liver. By observing changes in response to surgical stress on a liver under chronic stress, in addition to studying the limitations of adaptation and reaction of the liver to the surrounding environment, we can understand acceptable performance and limits possessed by a liver under stress. We are attempting to develop new diagnostic and treatment methods using bioimaging. The figure on the right shows liver oxidative stress directly after receiving external stress.
2) Obesity (metabolic syndrome) and liver stress: Obesity / fatty liver is thought to potentially stress organs and cells. In obese mice with fatty liver, acute liver injury and liver regenerative failure occur directly after surgical treatment for chronic liver injury and fatty liver.
In fatty livers responding to surgical stress, nucleic protein phosphorylation related to cell growth decreased, cell growth ability was lowered, and cell injury increased due to temporal oxidant stress increase. Determining the cause of this is important for promoting healthcare, especially preventive care.
Some chronic fatty liver is known to progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis, or liver cancer, and its mechanism is revealing. We succeeded in determining the mechanism of acute liver failure / impaired regeneration caused by chronic failure of fatty liver, surgery stress etc., by identifying the molecule (p62/SQSTM1) that plays a central role (see the figure on right). In a fatty liver, the expression of p62/SQSTM1 was reduced, which caused (1) increase of the molecules that induce liver cell failure, (2) decrease of a series of anti-oxidant molecules in the liver cells to induce chronic liver failure and transient strong oxidant stress, liver failure, and impaired liver regeneration after liver resection. Furthermore, it was found that (3) increase of apoptosis caused by decrease of anti-apoptosis molecular group and (4) non-responsiveness of the molecules that are important for cell survival is also important factors. This could be an important mechanism in progressing to NASH, which has been attracting attention recently regarding fatty liver.
Based on these research results, we aim to develop methods to prevent occurrence and progression of diseases such as NASH, not only from a drug development standpoint, but also from a preventative medicine perspective.
3) Imaging of bio-environment and phenomenon using "light": We utilize bioimaging with light in order to analyze dynamic pathologic change inside the body. Our goal is to develop a new molecular probe using light to visualize cell and tissue environment, or molecular functions, as a new diagnostic tool and treatment method. By lighting cells, we are trying to control bio-molecular and cell functions.
We aim to "develop mild diagnostic and treatment methods using light" by taking advantage of these technologies.

 

References

(1) "The Molecular Mechanism of Liver Injury / Regeneration - An Analysis through Bioimaging (Kanshougai saisei no bunshi mekanizumu to imeejingu kaiseki),” "Biochemistry (Seikagaku)" Michitaka Ozaki +84(8):685-692(2012)

(2) "Applied Research Frontiers in Glowing Bio ― View Stress with Light Imaging (Hikaru seibutu no ouyou kenkyuu saizensen – hikari imeejingu de sutoresu wo miru -)" "Biophilia” Adthree Publishing Co., Ltd. (Tokyo), Michitaka Ozaki 5 (4), 38-41 (2009)