Tadayoshi Karasawa

Assistant Professor , Center for Molecular Medicine, Jichi Medical University *Profile is at the time of the award.

2025Inamori Research GrantsBiology & Life sciences

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Research topics: Elucidating the regulatory mechanism of cell death with forward genetics targeting the lipid metabolism

Keyword

Summary: Necrosis was previously considered an accidental cell death. However, recent studies have suggested that necrosis can be induced as a form of regulated cell death (RCD), and necrotic RCD is involved in the progression of various diseases. Plasma membrane lipid metabolism is regarded as a potential target for the regulation of necrotic RCDs because they are characterized by plasma membrane destruction. In this study, we aim to identify the enzymes and lipid composition that determine the sensitivity of necrotic RCDs using forward genetics targeting enzymes involved in lipid metabolism.

Comment

I am grateful for the opportunity to work on this project, which will provide new insights into how lipid metabolism regulates necrotic RCDs.

Outline of Research Achievments

In this study, we aimed to elucidate the relationship between necrotic regulated cell death (RCD) and lipid metabolism, and to establish strategies for regulating necrotic RCD via lipid metabolism. To this end, we constructed a CRISPR library targeting genes　involved in lipid metabolism. Furthermore, we investigated the molecular mechanisms of pyroptosis, a necrotic RCD, triggered by inflammasome activation. We found that phosphatidylserine exposure is involved in plasma membrane rupture triggered by inflammasome activation.

Karasawa T et al. (2026) Inflammasome activation drives gasdermin-independent plasma membrane rupture by clustering ninjurin-1 in macrophages bioRxiv doi: https://doi.org/10.64898/2026.04.10.717393

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