Philippe G. Frank, Ph.D.


Assistant Professor
Stem Cell Biology and Regenerative Medicine

Telephone
215-503-9292

Office Address
933 BLSB
233 S. 10th St.

Email Address
Philippe.Frank@jefferson.edu

 

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.



Keywords: Diet and Cancer, Lipoprotein, Cholesterol, Caveolae, Vascular Disease.
 

PubMed Link For Frank PG


Selected Publications

Llaverias G, Danilo C, Mercier I, Daumer K, Capozza F, Williams TM, Sotgia F, Lisanti MP, Frank PG. Role of cholesterol in the development and progression of breast cancer. Am J Pathol. 178(1):402-12, 2011. ( Abstract )

Llaverias G, Danilo C, Wang Y, Witkiewicz AK, Daumer K, Lisanti MP, Frank PG. A Western-type diet accelerates tumor progression in an autochthonous mouse model of prostate cancer. Am J Pathol. 177(6):3180-91, 2010. ( Abstract )

Frank PG. Endothelial caveolae and caveolin-1 as key regulators of atherosclerosis. Am J Pathol. 177(2):544-6, 2010. ( Abstract )

Frank PG, Lisanti MP. ICAM-1: role in inflammation and in the regulation of vascular permeability. Am J Physiol Heart Circ Physiol. 295(3):H926-H927, 2008. ( Abstract )

Frank PG, Pavlides S, Lisanti MP. Caveolae and transcytosis in endothelial cells: role in atherosclerosis. Cell Tissue Res. 335(1):41-7, 2009. ( Abstract )

Frank PG, Pavlides S, Cheung MW, Daumer K, Lisanti MP. Role of caveolin-1 in the regulation of lipoprotein metabolism. Am J Physiol Cell Physiol. 295(1):C242-8, 2008. ( Abstract )

Frank PG, Hassan GS, Rodriguez-Feo JA, Lisanti MP. Caveolae and caveolin-1: novel potential targets for the treatment of cardiovascular disease. Curr Pharm Des. 13(17):1761-9, 2007. ( Abstract )

Frank PG, Lisanti MP. Caveolin-1 and liver regeneration: role in proliferation and lipogenesis. Cell Cycle. 6(2):115-6, 2007. ( Abstract )

Frank PG, Lisanti MP. Zebrafish as a novel model system to study the function of caveolae and caveolin-1 in organismal biology. Am J Pathol. 169(6):1910-2, 2006. ( Abstract )

Frank PG, Lisanti MP. Role of caveolin-1 in the regulation of the vascular shear stress response. J Clin Invest. 116(5):1222-5, 2006. ( Abstract )

Frank PG, Cheung MW, Pavlides S, Llaverias G, Park DS, Lisanti MP. Caveolin-1 and regulation of cellular cholesterol homeostasis. Am J Physiol Heart Circ Physiol. 291(2):H677-86, 2006. ( Abstract )

Frank PG, Lisanti MP. Defining lipid raft structure and function with proximity imaging. Am J Physiol Heart Circ Physiol. 290(6):H2165-6, 2006. ( Abstract )

Frank PG, Lisanti MP. Caveolin-1 and caveolae in atherosclerosis: differential roles in fatty streak formation and neointimal hyperplasia. Curr Opin Lipidol. 15(5):523-9, 2004. ( Abstract )

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. 24(1):98-105, 2004. ( Abstract )

Frank PG, Woodman SE, Park DS, Lisanti MP. Caveolin, caveolae, and endothelial cell function. Arterioscler Thromb Vasc Biol. 23(7):1161-8, 2003. ( Abstract )

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. 41(39):11931-40, 2002. ( Abstract )

Frank PG, Pedraza A, Cohen DE, Lisanti MP. Adenovirus-mediated expression of caveolin-1 in mouse liver increases plasma high-density lipoprotein levels. Biochemistry. 40(36):10892-900, 2001. ( Abstract )

Frank PG, Galbiati F, Volonte D, Razani B, Cohen DE, Marcel YL, Lisanti MP. Influence of caveolin-1 on cellular cholesterol efflux mediated by high-density lipoproteins. Am J Physiol Cell Physiol. 280(5):C1204-14, 2001. ( Abstract )

Frank PG, Marcel YL. Apolipoprotein A-I: structure-function relationships. J Lipid Res. 41(6):853-72, 2000. ( Abstract )
 

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