Research Interests
Genetic regulation of lipid and lipoprotein metabolism and molecular relationship to atherosclerosis.
Description of Research
The Rader laboratory is interested in 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.
Major ongoing projects include:
1) 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.
2) 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.
3) 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.
4) 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.
Research Lab:
6th floor, Biomedical Research Building (BRB) II/III
Clinical Research:
4th floor Andrew Mutch Building, Presbyterian Medical Center
Selected Publications
Degoma Emil M, Rader Daniel J: Novel HDL-directed pharmacotherapeutic strategies. Nature reviews. Cardiology 8(5): 266-77, May 2011.
Potteaux Stephane, Gautier Emmanuel L, Hutchison Susan B, van Rooijen Nico, Rader Daniel J, Thomas Michael J, Sorci-Thomas Mary G, Randolph Gwendalyn J: Suppressed monocyte recruitment drives macrophage removal from atherosclerotic plaques of Apoe-/- mice during disease regression. The Journal of clinical investigation 121(5): 2025-36, May 2011.
Bauer Robert C, Stylianou Ioannis M, Rader Daniel J: Functional validation of new pathways in lipoprotein metabolism identified by human genetics. Current opinion in lipidology 22(2): 123-8, Apr 2011.
Mehta Nehal N, Li Mingyao, William Dilusha, Khera Amit V, Derohannessian Stephanie, Qu Liming, Ferguson Jane F, McLaughlin Catherine, Shaikh Lalarukh Haris, Shah Rhia, Patel Parth N, Bradfield Jonathan P, He Jing, Stylianou Ioannis M, Hakonarson Hakon, Rader Daniel J, Reilly Muredach P: The novel atherosclerosis locus at 10q11 regulates plasma CXCL12 levels. European heart journal 32(8): 963-71, Apr 2011.
Rak Kimberly, Rader Daniel J: Cardiovascular disease: the diet-microbe morbid union. Nature 472(7341): 40-1, Apr 2011.
Townsend Raymond R, Anderson Amanda H, Chen Jing, Gadebegku Crystal A, Feldman Harold I, Fink Jeffrey C, Go Alan S, Joffe Marshall, Nessel Lisa A, Ojo Akinlolu, Rader Daniel J, Reilly Muredach P, Teal Valerie, Teff Karen, Wright Jackson T, Xie Dawei: Metabolic Syndrome, Components, and Cardiovascular Disease Prevalence in Chronic Kidney Disease: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study. American journal of nephrology 33(6): 477-484, Apr 2011.
Toh Sue-Anne, Millar John S, Billheimer Jeffrey, Fuki Ilia, Naik Snehal U, Macphee Colin, Walker Max, Rader Daniel J: PPARγ activation redirects macrophage cholesterol from fecal excretion to adipose tissue uptake in mice via SR-BI. Biochemical pharmacology 81(7): 934-41, Apr 2011.
Nijstad Niels, de Boer Jan Freark, Lagor William R, Toelle Markus, Usher David, Annema Wijtske, der Giet Markus van, Rader Daniel J, Tietge Uwe J F: Overexpression of apolipoprotein O does not impact on plasma HDL levels or functionality in human apolipoprotein A-I transgenic mice. Biochimica et biophysica acta 1811(4): 294-9, Apr 2011.
Edmondson Andrew C, Braund Peter S, Stylianou Ioannis M, Khera Amit V, Nelson Christopher P, Wolfe Megan L, Derohannessian Stephanie L, Keating Brendan J, Qu Liming, He Jing, Tobin Martin D, Tomaszewski Maciej, Baumert Jens, Klopp Norman, Döring Angela, Thorand Barbara, Li Mingyao, Reilly Muredach P, Koenig Wolfgang, Samani Nilesh J, Rader Daniel J: Dense Genotyping of Candidate Gene Loci Identifies Variants Associated With High-Density Lipoprotein Cholesterol. Circulation. Cardiovascular genetics 4(2): 145-155, Apr 2011.
Magge Sheela N, Stettler Nicolas, Koren Dorit, Levitt Katz Lorraine E, Gallagher Paul R, Mohler Emile R, Rader Daniel J: Adiponectin Is Associated with Favorable Lipoprotein Profile, Independent of BMI and Insulin Resistance, in Adolescents. The Journal of clinical endocrinology and metabolism Mar 2011.
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Last updated: 08/13/2012
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