Yasuko Iwakiri

BIOGRAPHY

ACADEMIC POSITION:
Assistant Professor of Medicine (Digestive Diseases)

RESEARCH INTERESTS::
1) Nitric oxide (NO) signaling in endothelial cells.
Endothelial cells produce NO by the enzyme, endothelial NO synthase (eNOS), which has unique subcellular localizations - cytosolic aspect of the Golgi apparatus and plasma membrane. Previously, we demonstrated that Golgi localization of eNOS influences local NO concentration, which creates favorable environment for the cysteine thiol modification of proteins by NO, known as S-nitrosylation, and influences endothelial cell function, such as protein trafficking (see Iwakiri et al. PNAS 2006). Thus, it was hypothesized that eNOS at the Golgi apparatus nitrosylates (modifies cysteine thiol of) the Golgi proteins and regulates Golgi proteins' functions such as trafficking. Recently we identified those Golgi proteins that are potentially considered as the targets for S-nirosylation, using subcellular proteomics approach. This project will determine some of important Golgi proteins that may be regulated by NO in endothelial cells.

2) Mechanisms of arterial abnormality observed in portal hypertension.
A hyperdynamic splanchnic and systemic circulation is typical of cirrhotic patients and has been observed in all experimental forms of portal hypertension. The hyperdynamic circulation is most likely initiated by arterial vasodilatation, leading to central hypovolemia, sodium retention and an increased intravascular volume. Arterial vasodilatation is regulated by a complex interplay of various vasodilator molecules and factors that influence the production of those vasodilator molecules. Nitric oxide (NO) has been recognized as the most important vasodilator molecule that mediates the excessive arterial vasodilatation observed in portal hypertension. eNOS is the primary NO producing enzyme responsible for excessive NO production and vasodilatation observed in the arterial splanchnic circulation in portal hypertension.My research focuses on elucidating the molecular mechanisms responsible for the up-regulation of eNOS in arteries of the splanchnic circulation in cirrhosis with portal hypertension.

HOME PAGE
http://medicine.yale.edu/intmed/people/yasuko_iwakiri.profile