Taichi
Taichi

Email: tyamamoto@chori.org
Phone: 510-428-3885 ext. 4635
Fax: 510-450-7910

CHORI Staff Directory
CHORI Intranet
CHORI News

 

Overview

My research program is focused on the structural and functional relationship of human low-density lipoprotein receptor (LDLR) and its binding partners, including apolipoprotein (apo) E and proprotein convertase subtilisin kexin type 9 (PCSK9). We are evaluating specific architectural features of these proteins with reference to their ability to modulate cholesterol homeostasis and lipid metabolism.

Studies have revealed the importance of the LDLR pathway in plasma cholesterol homeostasis. LDLR is a key player in an endocytic pathway that facilitates internalization of hepatically derived cholesterol-rich lipoproteins. The most recent regulatory protein for LDLR to be identified is PCSK9, a ninth member of the subtilisin-like proprotein convertase family of enzymes. Researchers initially identified three families with autosomal dominant hypercholesterolemia and premature coronary heart disease caused by missense or nonsense mutations in PCSK9. Some of these mutants show a remarkable correlation with reduced coronary heart disease (50~90% reduced incidence). In addition, two young African American women with total PCSK9 deficiency have been recently identified. Both subjects showed extremely low plasma cholesterol levels. PCSK9 likely represents a strong target for pharmacological prevention of premature atherosclerosis and coronary heart disease.

The goal of our research is to understand the molecular function of LDLR – PCSK9 interactions in cholesterol homeostasis. We anticipate that results obtained will provide new insight that may lead to new strategies to diagnose, prevent or treat therapeutic cardiovascular disease.


revised: Wednesday, March 25, 2009 4:50 PM

 

© 2005 Children's Hospital Oakland Research Institute
5700 Martin Luther King Jr Way • Oakland, California 94609
Phone 510-450-7600 • Fax 510-450-7910
Site MapDisclaimerCHORI IntranetEmail Webmaster