Nakatsu YuusukeTeikyo University Chiba Medical Center Clinical Professor Third Department of Internal Medicine Clinical Professor | ![]() | ||
Main Research Theme:
Regulation of Biological Functions and Disease Development by Prolyl Isomerases
Prolyl isomerases bind to various target proteins and regulate their functions by catalyzing cis-trans isomerization of proline residues. These enzymes are classified into the FKBP, Cyclophilin, and Parvulin families. Our research focuses on Pin1 and Pin4, members of the Parvulin family.
Pin1 interacts with distinct substrates in a tissue-specific manner and is involved in the development of various metabolic syndromes. In adipocytes, Pin1 contributes to obesity by suppressing lipolysis and thermogenesis (Nakatsu et al., Cell Reports, 2019; Nakatsu et al., Metabolism, 2021). In the liver, it is implicated in the onset of metabolic dysfunction–associated steatohepatitis (MASH) (Nakatsu et al., BBA Molecular Basis of Disease, 2025).
On the other hand, Pin1 also plays important roles in maintaining physiological functions, such as insulin secretion in pancreatic β-cells and exercise capacity in skeletal muscle (Nakatsu et al., J. Biol. Chem., 2017; Nakatsu et al., BBRC, 2024).
Currently, in addition to Pin1, we have begun investigating Pin4 (Inoue MK et al., BBA Molecular Cell Research, 2025) to elucidate the comprehensive regulatory mechanisms of biological functions by prolyl isomerases. We are also working on the development of novel therapeutic strategies targeting Pin1 and Pin4 inhibitors.