Phillip B. Hylemon , Ph.D.
Professor, Lipid Research Group

Phone: (804) 828-2331, -2332
Dept. Fax: (804) 828-9946
e-mail: hylemon@vcu.edu

Address:
Department of Microbiology & Immunology
Virginia Commonwealth University
P.O. Box 980678
1217 E. Marshall Street, 523 Medical Sciences Building
Richmond, VA 23298-0678

Professional Experience

• B.S., 1967, Barton College
• Ph.D., 1972, Virginia Polytechnic Institute and State University
• Postdoctoral, 1973, Medical College of Virginia/Virginia Commonwealth University

Research Interests:

Research efforts in my laboratory center around two major areas: 1) Studies of the Biochemistry and Genetics of secondary bile acids formation by intestinal anaerobic bacteria: implications for cholesterol gallstone formation in man; 2) Regulation of bile acid biosynthesis in primary adult rat hepatocytes in culture and bile acid initiated cell signaling in regulation of hepatic gene expression. Deoxycholic acid is make exclusively by a small population of intestinal anaerobic bacteria. Increased deoxycholic acid formation has been associated with and increased risk for cholesterol gallstone formation and colon cancer. Hepatic conversion of cholesterol to bile acids is a major pathway for removal of cholesterol from the body. Bile acids repress their own biosynthesis by transcriptionally down regulating cholesterol 7a -hydroxylase and sterol 27-hydroxylase the rate limiting enzyme in the two major bile acid biosynthetic pathways. Our efforts in this area are direct toward an understanding of how the hepatocyte "senses" the concentration of composition of the bile acid pool and represses gene transcription.

Selected Publications:

Berr, F., G.A. Kullok-Ublick, G. Paumgartner, W. Monzing and P.B. Hylemon. Alteration of intestinal microflora may cause cholesterol gallstones by excessive in put of deoxycholic acid in man. Gastroenterology, 111:16-1620 (1996).

Mallonee, D.H. and P.B. Hylemon. Sequencing and expression of a gene encoding a bile acid transporter from Eubacterium sp. VPI 12708. J. Bacteriol. 178:7053-7058 (1996).

Rao, Y-P, Z. R. Vlahcevic, R. T. Stravitz, D.H Mallonee, J. Mullick, N.G. Avadhani and P.B. Hylemon. Down-regulation of the rate hepatic sterol 27-hydroxylase gene by bile acids in transfected primary hepatocytes: Possible role of hepatic nuclear factor 1a. J. Steroid Biochem & Mol. Biol. 70:1-14 (1999).

Gupta S., Stravitz RT , P. Dent and P.B. Hylemon. Down-regulation of cholesterol 7a-hydroxylase (CYP7A1) gene expression by bile acids in primary rat hepatocytes is mediated by the c-Jun N-terminal kinase pathway. J. Biol. Chem. 276:15816-15822 (2001).

Rao Y-P, E. J. Studer, R. T. Stravitz, S. Gupta, L. Qiao, P. Dent and P.B. Hylemon. Activation of the Raf-1/MEK/ERK cascade by bile acids occurs via the epidermal growth factor receptor in primary rat hepatocytes. Hepatology 35:307-315, 2002.

Gerbod-Giannone M.C., A. Del Castillo-Olivares, S. Janciauskiene, G. Gil. and P.B. Hylemon. Supression of cholesterol 7a-hydroxylase transcription and bile acid synthesis by an alpha 1-antitrypsin peptide via interaction with alpha 1-fetoprotein transcription factor. J. Biol. Chem. 277:42973-42980 (2002).

Pandak, W.M., S. Ren, D. Marques, E. Hall, K. Redford, D. Mallonee, P. Bohdan, D. Heuman, G. Gil, and P.B. Hylemon. Transport of cholesterol into mitochondria is rate-limiting for bile acid synthesis via the alternative pathway in primary rat hepatocytes. J. Biol. Chem. 277:48158-48164 (2002).

Ren S, Marques D, Gil G, Redford K, Vlahcevic ZR, Hylemon PB:  Regulation of oxysterol 7 alpha-hydroxylase (CYP7B1) in rat.  Metabolism 2003; 52:636-642.

Gupta S, Natarajan R, Payne SG, Studer EJ, Spiegel S, Dent P, Hylemon PB:  Deoxycholic acid activates the c-jun-N-terminal kinase (JNK) pathway via FAS receptor activation in primary hepatocytes: Role of acidic sphingomyelinase-mediated ceramide generation in FAS receptor activation.  Journal of Biological Chemistry 2004; 279:5821-5828.

Han SI, Studer E, Gupta S, Fang Y, Qiao L, Li W, Grant S, Hylemon PB, Dent P:  Bile acids enhance the activity of the insulin receptor and glycogen synthase primary rodent hepatocytes.  Hepatology 2004; 39:456-462.

Ren S, Hylemon PB, Marques D, Hall E, Redford K, Gil G, Pandak WM:  Effect of increasing the expression of cholesterol transporters (StAR, MLN64, and SCP2) on bile acid synthesis.  Journal of Lipid Research 2004; 45:2123-2131.

Fang Y, Han SI, Mitchell C, Gupta S, Studer E, Grant S, Hylemon PB, Dent P:  Bile acids induce mitochondrial ROS, which promote activation of receptor tyrosine kinases and signaling pathways in rat hepatocytes.  Hepatology 2004; 40:961-971.

Ren S, Hylemon PB, Marques D, Gurley E, Bohdan P, Hall E, Redford K, Gil G, Pandak WM:  Overexpression of cholesterol transporter StAR increases in vivo rates of bile acid synthesis in the rat and mouse.  Hepatology 2004; 40:910-917.

Zhou H, Pandak WM, Lyall V, Natarajan R, Hylemon PB.  HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease.  Molecular Pharmacology 2005; 68(3):690-700.

Rodriguez-Agudo D, Ren S, Hylemon PB, Redford K, Natarajan R, Del Castillo A, Gil G, Hylemon PB.  Human StarD5, a cytosolic StAR-related lipid binding protein.  Journal of Lipid Research 2005; 46(8):1615-1623.

Dent P, Han SI, Mitchell C, Studer E, Yacoub A, Grandis J, Grant S, Krystal GW, Hylemon PB. Inhibition of insulin/IGF-1 receptor signaling enhances bile acid toxicity in primary hepatocytes. Biochemical Pharmacology. 2005; 70(11):1685-96.

Dent P, Fang Y, Gupta S, Studer E, Mitchell C, Spiegel S, Hylemon PB.  Conjugated bile acids promote ERK1/2 and AKT activation via a pertussis toxin-sensitive mechanism in murine and human hepatocytes.  Hepatology 2005; 42(6):1291-9.

Ridlon JM, Kang D-J, Hylemon PB.  Bile salt biotransformations by intestinal bacteria.  Journal of Lipid Research 2006; 47(2):241-259.

Ren S, Hylemon P, Zhang Z-P, Rodriguez-Agudo D, Marques D, Li X, Zhou H, Gil G, Pandak WM.  Identification of a Novel Sulfonated Oxysterol, 5-Cholesten-3b, 25-Diol 3-Sulfonate, in Hepatocyte Nuclei and Mitonchondria.  Journal of Lipid Research 47:1081-1090, 2006.

Rodriguez-Agudo D, Ren S, Hylemon PB, Montanez R, Redford K, Natarajan R, Medina MA, Gil G, Pandak WM.  Localization of StarD5 cholesterol binding protein.  Journal of Lipid Research 47:1168-1175, 2006.

Li X, Hylemon P, Pandak WM, Ren S.  Enzyme activity assay for cholesterol 27-hydroxylase in mitochondria.  Journal of Lipid Research 47:1507-1512, 2006.

Zhou H, Gurley EC, Jarujaron S, Ding H, Fang Y, Xu Z, Pandak WM, Hylemon P.  HIV protease inhibitors activate the unfolded protein response and disrupt lipid metabolism in primary hepatocytes.  Am J Physiol Gastrointest Liver Physiol. 291(6):G1071-1080, 2006.

Fang Y, Studer E, Mitchell C, Grant S, Pandak WM, Hylemon P.  Conjugated bile acids regulate hepatocyte glycogen synthase activity in vitro and in vivo via Gαi signaling.  Molecular Pharmacology 71:1122-1128, 2007.

Ren S, Li X, Rodriguez-Agudo D, Gil G, Hylemon P, Pandak WM.  Sulfated oxysterol, 25HC3S, is a potentt regulator of lipid metabolism in human hepatocytes.  Biochem. Biophys. Res. Commun. 360:802-808, 2007.

Xu Z, Tavares-Sanchez OL, Li Q, Fernando J, Rodriguez CM, Studer EJ, Pandak WM, Hylemon PB, Gil G.  Activation of Bile Acid Biosynthesis by the p38 Mitogen-Activated Protein Kinase (MAPK).  Journal of Biological Chemistry 282(34):24607-24614, 2007.

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Date Last Modified: 07/10/2008
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