Center for Orphan Disease Research and Therapy
Daniel J. Rader, M.D.
Edward S. Cooper, MD/Norman Roosevelt & Elizabeth Meriwether McLure Professor of Medicine and Pharmacology
Chief, Division of Translational Medicine and Human Genetics
Director, Preventive Cardiovascular Medicine and Lipid Clinic
Director, Clinical and Translational Research Center
Associate Director, Institute for Translational Medicine and Therapeutics
Director, Cardiovascular Metabolism Unit, Institute for Diabetes, Obesity, and Metabolism
Dr. Rader research interest focuses on genetic regulation of lipid and lipoprotein metabolism and molecular relationship to atherosclerosis. Dr. Radar lab interest focuses on genetic and inflammatory factors that regulate the metabolism and function of plasma lipoproteins and their interaction with the vessel wall in promoting and inhibiting atherogenesis. A variety of basic cell and molecular laboratory techniques, mouse models, and clinical research approaches are used in addressing these questions.
Dr. Rader's major ongoing projects are:
- Inflammatory and genetic factors that regulate the in vivo metabolism of HDL and other lipoproteins. A major current focus is that extracellular lipases are important physiologic and pathophysiologic regulators of lipoprotein metabolism and function and that their expression is both genetically determined and influenced by inflammatory factors. We have cloned several new members of the lipoprotein lipase gene family and are investigating their function and regulation.
- Molecular and cellular mechanisms by which HDL-associated proteins inhibit atherogenesis and induce regression of atherosclerotic lesions. Somatic gene transfer of HDL-associated proteins is used in mouse models of atherosclerosis in order to study their effects on atherogenesis in vivo. Tissue culture models have been developed in order to reconstruct cellular aspects of the atherosclerotic process in vitro and determine anti-inflammatory effects of HDL proteins.
- Dietary and genetic regulation of hepatic lipoprotein production. Gene transfer, transgenic, and cell culture approaches are used to study the interaction between specific genes, such as the microsomal transfer protein and diacylglycerol acyltransferase, and dietary manipulation in the regulation of hepatic apoB production in mice. Lipoprotein kinetic studies are also performed in humans using endogenous labeling of apolipoproteins with stable isotopically labeled leucine.
- Genetic factors associated with premature atherosclerotic disease and high or low levels of HDL cholesterol. Subjects with family history of premature coronary disease or with extremes of HDL cholesterol are recruited and phenotyped for cardiovascular risk factors and clinical and subclinical atherosclerosis. Candidate genes are investigated for their association with subclinical atherosclerosis or variation in HDL cholesterol levels and linkage analysis of sib pairs and large pedigrees will be performed. The overall focus of our research effort is basic cell and molecular laboratory science with translation into animal experiments and ultimately into patient-oriented research in the areas of lipoprotein metabolism and premature atherosclerosis.