beigneux laboratory | fong laboratory
 

 UCLA Cellular and Molecular Cardiology Unit 

 Stephen G. Young, M.D., Director 

 


Research

Our group discovered an endothelial cell protein, GPIHBP1, that is required  for the processing of triglyceride-rich lipoproteins. Genetic defects in GPIHPB1 cause severe hypertriglyceridemia.  Over the next few years, we plan to pursue the cell biology, structure, and clinical relevance of GPIHPB1.

We have also investigated the importance of lipid modifications of proteins.  Much of this work is focused on the nuclear lamins, which are building blocks for the nuclear lamin A--a structural scaffolding for the cell nucleus. A defect in one of the nuclear lamins, prelamin A, leads to progeria, a “precocious aging” syndrome in children.  The prelamin A in children with progeria cannot be processed normally, resulting in the accumulation of a “lipidated”  prelamin A. We hypothesized that drugs designed to block the lipid modification would ameliorate the disease phenotypes of progeria. To test this hypothesis, we generated two gene-targeted mouse models of progeria. A drug designed to block the lipidation of prelamin A reduced the severity of the disease phenotypes in both models. Drug trials in humans are currently underway.

Over the next few years, we plan to define the in vivo importance of two other nuclear lamins, lamin B1 and lamin B2. 

Our laboratory focuses on molecules relevant to human disease. We make use of a wide variety of techniques in molecular and cellular biology,  including the creation of genetically modified mouse models.


 

©2010 UCLA Cellular and Molecular Cardiology Unit