We are working on further exploring our original discoveries in the fields of signal transduction and cell death control by linear ubiquitin chains and cellular iron metabolism. We also trying to make brand-new discoveries - i.e., independently of any previous research.

Kazuhiro Iwai, M.D., Ph.D.

Molecular and Cellular Physiology
Graduate School of Medicine Kyoto University

After relocating my laboratory to Kyoto University in 2012, today I feel truly grateful that in these years I was so fortunate to be able to practice and enjoy science with so many brilliant young students.

I now believe that one key characteristic of our research is to "find scientifically important questions and elucidate them". In the process of elucidating purely biochemical systems, we discovered an entirely novel ubiquitin chain - the linear ubiquitin chain - and the LUBAC ubiquitin ligase complex that specifically generates this type of chain.

It came as a great surprise to us to discover that the linear ubiquitin chain plays crucial roles in the regulation of inflammatory responses. We were able to elucidate that dysregulated generation of the linear chain underlies the development of various diseases including immunodeficiency, autoinflammatory diseases, and malignant tumors. In addition, the linear chain is also important for protection from pathogens and indeed, several pathogenic microorganisms possess toxins that selectively interfere with the generation of linear ubiquitin chains. Therefore, as of right now, our laboratory's focus has shifted from research on ubiquitin itself to the study of immune diseases, malignancies, and infection control through inflammation control.

As I myself started my career as a clinician, I gladly welcome this recent shift in the focus of our laboratory. From now on, I would like to provide a laboratory environment in which young scientists and researchers from all clinical departments can work together and disseminate new ideas and knowledge from Kyoto University.

The second main research focus of our laboratory is cellular iron metabolism. I started studying iron metabolism as a post-doc at NIH, USA in 1993. Although I continued working on iron metabolism after coming back to Japan from the US in 1996, it was difficult to attract much attention for iron metabolism in the Japanese biomedical community. However, in recent years, cellular iron metabolism has been attracting tremendous attention due to the discovery of ferroptosis, a form of cell death that specifically depends on iron. Given these circumstances, we continue to conduct iron research based on our own unique perspective since we realize that various critical aspects in iron research still remain overlooked.

The precise description of each of the research topics we currently focus on are described on this homepage. I hope that as many people as possible will become interested in our research, join the laboratory, and conduct research from their own original perspective.

I will put forth my best efforts so that as many researchers as possible will graduate from our laboratory with great self-enabled "logical thinking skills", self-elicited "courage", and self-imposed sense of "responsibility". To this end, I eagerly await the participation of motivated young people in our laboratory.

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