Akira Nakai Professor Graduate School of Medicine Biochemistry & Molecular Biology E-mail: anakai@yamaguchi-u.ac.jp URL: http://ds22.cc.yamaguchi-u.ac.jp/~seika2/ T E L : +81-836-22-2214 F A X : +81-836-22-2315

Research Activities

Protein homeostasis in cells enables healthy cells and organismal development and aging, and protects against diseases. Dr. Nakai aims to understand the molecular mechanisms of protein homeostasis by focusing on heat shock response and heat shock transcription factors (HSFs), and to find therapeutic strategies for stress-related diseases such as neurodegenerative diseases and cancers. He and his colleagues found that HSF1 suppresses protein aggregation through regulation of yet unknown genes as well as heat shock genes, and that overexpression of HSF1 improved the lifespan of the protein misfolding disease model mice. He would like to find novel mechanisms that suppress protein misfolding.

　 Dr. Nakai has also shown mechanisms of how heat shock transcription factors support cell survival against detrimental effects of various stresses by generating chicken B lymphocyte DT40 cells deficient for HSF1 and HSF3. Paradoxically, he also observed that HSF1 activates expression of pro-apoptotic genes in addition to anti-apoptotic heat shock genes. He is trying to understand the patho-physiological significance of these pathways.

　 Furthermore, he also generated HSF1-null and HSF4-null mice for his experiments. Analysis of these mice revealed developmental abnormalities in the lens and olfactory epithelium, indicating that HSFs are essential for development of the sensory organs, and also implies that some tissue developmental pathways are linked to stress response. His team is examining the molecular links between protein homeostasis and development.

Message

　A cell is a fundamental unit of life. Researchers in Biochemical and Molecular Biological fields are trying to understand elementary processes in cells that regulate cell growth, differentiation, death, and responses to stimuli. Discovery of a new elementary process contribute not only on establishing a novel concept but also on understanding and treatment of diseases. Our laboratory welcomes researchers who are enthusiastic to find out the truth in nature.