Kazumi Ishimura-Oka, MD
Baylor College of Medicine
Regulation of lipid metabolism
The primary goal of my research is to define the mechanisms by
which lipid metabolism is regulated in normal and pathological conditions.
We have been studying the physiological roles of enzymes and lipoprotein
receptors involved in complex lipoprotein dynamics employing the
molecular biology techniques. The protein of our current major interests
is lipoprotein lipase (LPL). We have generated adipose tissue-specific-LPL
transgenic mice. Using this animal model, we will determine the
tissue-specific effects of LPL in lipid metabolism with regards
to metabolic disorders such as obesity, atherosclerosis and diabetes.
Other protein of interests is very low density lipoprotein receptor
(VLDLR). Overexpression of VLDLR has been shown to ameliorate hypercholesterolemia
in LDL receptor knockout mice using adenovirus-mediated somatic
gene transfer. We plan to study the role of VLDLR in obesity development
and lipid nutrient delivery. Our study will help understand the
molecular basis for lipid abnormalities and develop gene therapy
for genetic disorders.
Ishimura-Oka K, Faustinella F, Kihara S, Smith LC, Oka K, Chan
L. A missense mutation (Trp86 Arg) in exon 3 of the lipoprotein
lipase: a cause of familial chylomicronemia. Am J Hum Genet 1992;50:1275-1280.
Kobayashi K, Oka K, Teng BB, Ishimura-Oka k, Forte T, Ishida B,
Chan L. Adenovirus-mediated gene transfer of VLDL receptor reversed
hypercholesterolemia in mice lacking LDL receptor. J Biol Chem 1996;224:975-982.
Oka K, Ishimura-Oka K, Chu MJ, Chan L. Transcription of the human
Hepatic lipase gene is modulated by multiple negative elements in
HepG2 cells. Gene 1996;180:69-80.
Oka K, Kobayashi K, Kovar M, Martinez J, Teng BB, Ishimura-Oka
K, Chan L. Tissue- specific inhibition of apolipoprotein B mRNA
editing in the liver by adenovirus mediated transfer of a dominant
negative mutant APOBEC-1 lead to increased low density lipoprotein
in mice. J Biol Chem 1997;272:1456-1460.