The World Premier International Immunology Frontier Research Center, which belongs to the University of Osaka, Japan, appointed Argentine scientist Matías José Caldez as a Specialized Researcher (Advanced-Postdoc) to continue its research on liver damage, metabolism and immunology.
With a vast international career, Caldez began his research on cancer using bioinformatics tools to analyze how common mutations found in breast and prostate cancer affect the function of molecules, in Argentina. Then, he worked as a researcher at the Institute of Cellular and Molecular Biology, which is one of the research institutes of the Agency of Science Technology and Research, A*STAR, Singapore. During his PhD, he studied the metabolic modifications of the liver cells, and what happens when the liver suffers some damage.
His latest discovery, using mouse models with genetic modifications, is a new metabolic response when liver cells do not work well. His finding helps to understand how liver cells change their metabolism during organ regeneration.
“When the liver suffers some damage, its cells can divide normally to recover the functions of the organ. However, when the liver is sick, as is the case with people suffering from fatty liver or cirrhosis, the cells cannot divide normally. This has an impact on the recovery of patients after liver transplantation, which is one of the recommended first-line therapies for patients suffering from liver problems such as fatty liver,” Caldez explained.
Caldez and his colleagues wondered if there is any relationship between the cell division of the liver cells and their metabolism. “Then we restored to an innovative strategy with which we inhibited cell division in mice using methods by which we can eliminate genes specifically in liver cells. These genetically modified mice carry mutations in a gene called Cdk1, which is essential for cell division. Then we use molecular biology methods with which we quantify the changes in all the genes and molecules involved in the metabolism (metabolites); and with computational models, we integrate this enormous amount of data to see what are the central changes in the metabolism when the liver cells cannot divide, and when they divide normally during the regeneration of the liver after a deep damage,” he explained.
In particular, it was discovered that when cells do not divide well, they can induce regeneration, through a new type of regeneration by cell growth. In this process there is a profound change in the metabolism of carbohydrates with a significant increase in amino acid metabolism. Finally, they modified the surgery protocols in mice to develop scanning of the metabolic pathways using advanced molecular scanning analysis.
This discovery helps significantly to understand how liver cells change their metabolism during liver regeneration. “We are very happy with our results because we were able to combine state-of-the-art technology with advanced molecular imaging studies to provide a detailed description of the metabolic changes during tissue regeneration in the liver. This has direct implications in the clinic, especially for patients who require liver transplantation,” said the researcher, who did this work under the direction of Professor Philipp Kaldis.
The work was published in the prestigious Developmental Cell magazine of the Cell Press group, and is the joint contribution of a large work team, with researchers from Singapore, Switzerland, China and the United Kingdom. Thanks to these results, Caldez was hired by the famous immunologist Professor Shizuo Akira, director of the World Premier International Immunology Frontier Research Center. His current work focuses on the development of immunotherapies to improve liver regeneration, and works in collaboration with the laboratory of Dr. Mikael Martino, of the Australian Regenerative Medicine Institute (Monash University, Melbourne, Australia).
Source: Agencia ID
