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Thomas Jefferson University - Philippe Frank, Ph.D.
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Philippe Frank, Ph.D.
Cancer Biology
Assistant Professor
Thomas Jefferson University
Department of Cancer Biology
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Mailing Address
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233 S. 10th Street, Rm933
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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Plasma lipoproteins, lipid transport, and atherosclerosis
Caveolae are 50-100 nm cell surface plasma membrane invaginations observed in terminally differentiated cells. They are characterized by the presence of the protein marker caveolin-1. Caveolae and caveolin-1 are present in almost every cell type that has been implicated in the development of an atheroma. These include endothelial cells, macrophages, and smooth muscle cells. Caveolae and caveolin-1 are involved in regulating several signal transduction pathways and processes that play important roles in atherosclerosis.
Heart disease is a leading cause of death in the United States and the Western World. A deep understanding of the events leading to heart disease is necessary in order to prevent and properly treat this deadly illness. one important clue is the role of fat and especially cholesterol in this process. High blood cholesterol levels are a major risk factor for heart disease, and the underlying disease process --more broadly termed atherosclerosis.During this process, the bad cholesterol is deposited in the blood vessels, leading to the formation of a blockage. Ultimately, we must understand the mechanisms by which occlusions form to prevent their development. Recent studies using genetically-engineered mice (Cav-1(-/-) knock-out animals) have now clearly demonstrated a role for caveolin-1 and caveolae in the development of atherosclerosis. In fact, they suggest a rather complex one, either pro-atherogenic or anti-atherogenic, depending on the cell type examined. For example, in endothelial cells, caveolin-1 and caveolae may play a pro-atherogenic role by promoting the transcytosis of low-density lipoprotein (LDL) particles from the blood to the sub-endothelial space. In contrast, in smooth muscle cells, caveolin-1s ability to negatively regulate cell proliferation (neointimal hyperplasia) may be anti-atherogenic. In addition, macrophage caveolin-1 may have a protective effect by preventing cholesteryl ester accumulation in macrophages.
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Keywords
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Atherosclerosis, Lipoprotein, Atherosclerosis, Vascular diseases.
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Publications
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- PubMed Link For Frank PG
- Selected publications:
- Frank PG, S Pavlides, and MP Lisanti. Caveolae and Transcytosis in Endothelial Cells: Role in Atherosclerosis. Cell & Tissue Res. 2009. 335(1):41-47.
- Frank PG, and MP Lisanti. ICAM-1, role in inflammation and in the regulation of vascular permeability. Am J Physiol Heart Circ Physiol. 2008. 295(3):H926-927.
- Frank PG, S Pavlides, MW Cheung, K Daumer, and MP Lisanti. Role of Caveolin-1 in the Regulation of Lipoprotein Metabolism. Am J Physiol Cell Physiol. 2008. 295(1):C242-248.
- Frank, PG.; GS Hassan, JA Rodriguez-Feo, MP Lisanti. Caveolae and Caveolin-1: Novel Potential Targets for the Treatment of Cardiovascular Disease. Curr Pharm Des. 2007. 13(17):1761-1769.
- Frank PG and Lisanti MP. Caveolin-1 and Liver Regeneration: Role in Proliferation and Lipogenesis Cell Cycle 2007. 6(2):115-6.
- Frank PG, Lisanti MP. Role of caveolin-1 in the regulation of the vascular shear stress response. J Clin Invest. 2006;116(5):1222-1225. Reprint
- Frank PG, Cheung MW, Pavlides S, Llaverias G, Park DS, Lisanti MP. Caveolin-1 and the Regulation of Cellular Cholesterol Homeostasis. Am J Physiol Heart Circ Physiol 2006 291(2):H677-686.
- Frank PG, Lisanti MP. Editorial Focus on Probing Lipid Rafts with Proximity Imaging: Actions of Proatherogenic Stimuli. Am J Physiol Heart Circ Physiol. 2006 Jan 20; In press.
- Hassan GS, Williams TM, Frank PG, Lisanti MP. Caveolin-1 Deficient (-/-) Aortic Smooth Muscle Cells Show Cell Autonomous Abnormalities in Proliferation, Migration, and Endothelin-based Signal Transduction. Am J Physiol Heart Circ Physiol. 2006 Jan 13; In press
- Williams TM, Hassan GS, Li J, Cohen AW, Medina F, Frank PG, Pestell RG, Di Vizio D, Loda M, Lisanti MP. Caveolin-1 promotes tumor progression in an autochthonous mouse model of prostate cancer: genetic ablation of Cav-1 delays advanced prostate tumor development in tramp mice. J Biol Chem. 2005 Jul 1;280(26):25134-45.
- Frank PG, Lisanti MP. Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol. 2004 Oct;15(5):523-9.
- Hassan GS, Jasmin JF, Schubert W, Frank PG, Lisanti MP. Caveolin-1 deficiency stimulates neointima formation during vascular injury. Biochemistry. 2004 Jul 6;43(26):8312-21.
- Frank PG, Lee H, Park DS, Tandon NN, Scherer PE, Lisanti MP. Genetic ablation of caveolin-1 confers protection against atherosclerosis. Arterioscler Thromb Vasc Biol. 2004 Jan;24(1):98-105.
- Frank PG, Woodman SE, Park DS, Lisanti MP. Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1161-8.
- Frank PG, Marcel YL, Connelly MA, Lublin DM, Franklin V, Williams DL, Lisanti MP. Stabilization of caveolin-1 by cellular cholesterol and scavenger receptor class B type I. Biochemistry. 2002 Oct 1;41(39):11931-40.
- Frank PG, Pedraza A, Cohen DE, Lisanti MP. Adenovirus-mediated expression of caveolin-1 in mouse liver increases plasma high-density lipoprotein levels. Biochemistry. 2001 Sep 11;40(36):10892-900.
- Frank PG, Marcel YL. Apolipoprotein A-I: structure-function relationships. J Lipid Res. 2000 Jun;41(6):853-72.
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Individual Expertise profile of
Philippe Frank, Ph.D., Copyright © Philippe Frank, Ph.D..
Last Updated
by Philippe Frank, Ph.D. : Monday, October 12, 2009 5:52:10 PM
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