Profile

Lawrence L. Rudel, Ph.D.Wake Forest School of Medicine

Lawrence L. Rudel, Ph.D.

Professor,



Contact Information

Academic: 336-716-2823 | Department: 336-716-2823

Email: lrudel@wakehealth.edu

Education & Training

  • B.S., Colorado State University , 1963
  • M.S., Univ Of Arkansas For Medical Sci , 1965
  • Ph.D., Univ Of Arkansas For Medical Sci , 1969
  • Fellowship, University Toronto Med-Canada, 1971
  • Fellowship, University of California-San F, 1973

Memberships

  • Am Assn Of Advancement Of Scie
  • Am Assn Of Pathologists
  • Aha - Council On Arteriosclero
Lawrence L. Rudel, Ph.D.

Lawrence L. Rudel, Ph.D.

Professor, Molecular Medicine
WFU Primate Center
Biochemistry
Translational Science Institute

Research Interests

atherosclerosis/thrombosis, drugs/therapeutic agents pharm, immunology/allergy/inflammatio, metabolism, model development, nutrition, transgenics

Contact Information

Academic: 336-716-2823 | Department: 336-716-2823

Email: lrudel@wakehealth.edu

Recent Publications

Marshall SM, Kelley KL, Davis MA, Wilson MD, McDaniel AL, Lee RG, Crooke RM, Graham MJ, Rudel LL, Brown JM, Temel RE. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice. PLoS One. 2014;9(1):e84418.

Marshall SM, Gromovsky AD, Kelley KL, Davis MA, Wilson MD, Lee RG, Crooke RM, Graham MJ, Rudel LL, Brown JM, Temel RE. Acute sterol o-acyltransferase 2 (SOAT2) knockdown rapidly mobilizes hepatic cholesterol for fecal excretion. PLoS One. 2014;9(6):e98953.

Rong JX, Blachford C, Feig JE, Bander I, Mayne J, Kusunoki J, Miller C, Davis M, Wilson M, Dehn S, Thorp E, Tabas I, Taubman MB, Rudel LL, Fisher EA. ACAT inhibition reduces the progression of preexisting, advanced atherosclerotic mouse lesions without plaque or systemic toxicity. Arterioscler Thromb Vasc Biol. 2013;33(1):4-12.

Ma L, Murea M, Snipes JA, Marinelarena A, Kruger J, Hicks PJ, Langberg KA, Bostrom MA, Cooke JN, Suzuki D, Babazono T, Uzu T, Tang SC, Mondal AK, Sharma NK, Kobes S, Antinozzi PA, Davis M, Das SK, Rasouli N, Kern PA,. An ACACB variant implicated in diabetic nephropathy associates with body mass index and gene expression in obese subjects. PLoS One. 2013;8(2):e56193.

Ohtawa M, Yamazaki H, Ohte S, Matsuda D, Ohshiro T, Rudel LL, Omura S, Tomoda H, Nagamitsu T. Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 1. Bioorg Med Chem Lett. 2013;23(5):1285-1287.

Bura KS, Lord C, Marshall S, McDaniel A, Thomas G, Warrier M, Zhang J, Davis MA, Sawyer JK, Shah R, Wilson MD, Dikkers A, Tietge UJ, Collet X, Rudel LL, Temel RE, Brown JM. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice. J Lipid Res. 2013;54(6):1567-1577.

McDaniel AL, Alger HM, Sawyer JK, Kelley KL, Kock ND, Brown JM, Temel RE, Rudel LL. Phytosterol feeding causes toxicity in ABCG5/G8 knockout mice. Am J Pathol. 2013;182(4):1131-1138.

Ohtawa M, Yamazaki H, Matsuda D, Ohshiro T, Rudel LL, Omura S, Tomoda H, Nagamitsu T. Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 2. Bioorg Med Chem Lett. 2013;23(9):2659-2662.

Ohtawa M, Yamazaki H, Ohte S, Matsuda D, Ohshiro T, Rudel LL, ?mura S, Tomoda H, Nagamitsu T. Synthesis and structure-activity relationship of pyripyropene A derivatives as potent and selective acyl-CoA:cholesterol acyltransferase 2 (ACAT2) inhibitors: part 3. Bioorg Med Chem Lett. 2013;23(13):3798-3801.

Voruganti VS, Jorgensen MJ, Kaplan JR, Kavanagh K, Rudel LL, Temel R, Fairbanks LA, Comuzzie AG. Significant genotype by diet (G X D) interaction effects on cardiometabolic responses to a pedigree-wide, dietary challenge in vervet monkeys (Chlorocebus aethiops sabaeus). Am J Primatol. 2013;75(5):491-499.

Ma L, Snipes JA, Murea M, Antinozzi PA, Shelness GS, Saleem M, Satchell SC, Banas B, Mathieson PW, Kretzler M, Petrovic S, Ross MD, Pollak MR, Rudel L, Parks JS, Freedman BI. ApoL1 protein in non-diseased human podocytes: endogenous synthesis versus uptake? [abstract]. J Am Soc Nephrol. 2013;24(Abstract Suppl):557A.

Melchior JT, Sawyer JK, Kelley KL, Shah R, Wilson MD, Hantgan RR, Rudel LL. LDL particle core enrichment in cholesteryl oleate increases proteoglycan binding and promotes atherosclerosis. J Lipid Res. 2013;54(9):2495-2503.


Owens AP III, Passam RH, Antoniak S, Marshall SM, McDaniel AL, Rudel L, Williams JC, Hubbard BK, Dutton J-A, Wang J, Tobias PS, Curtiss LK, Daugherty A, Kirchhofer D, Luyendyk JP, Moriarty PM, Nagarajan S, Furie BC, Furie B, Johns DG, Temel RE, Mackman N. Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin. J Clin Invest. 2012;122(2):558-568.

Miller CD, Thomas MJ, Hiestand B, Samuel MP, Wilson MD, Sawyer J, Rudel LL. Cholesteryl esters associated with acyl-CoA:cholesterol acyltransferase-2 predict coronary arter stenosis in patients with symptoms of acute coronary syndrome [abstract]. Acad Emerg Med. 2012;19(Suppl 1):S150.

Baum SJ, Kris-Etherton PM, Willett WC, Lichtenstein AH, Rudel LL, Maki KC, Whelan J, Ramsden CE, Block RC. Fatty acids in cardiovascular health and disease: a comprehensive update. J Clin Lipidol. 2012;6(3):216-234.

Miller CD, Thomas MJ, Hiestand B, Samuel MP, Wilson MD, Sawyer J, Rudel LL. Cholesteryl esters associated with Acyl-CoA:cholesterol acyltransferase predict coronary artery disease in patients with symptoms of acute coronary syndrome. Acad Emerg Med. 2012;19(6):673-682.

Zhang J, Kelley KL, Marshall SM, Davis MA, Wilson MD, Sawyer JK, Farese RV Jr, Brown JM, Rudel LL. Tissue-specific knockouts of ACAT2 reveal that intestinal depletion is sufficient to prevent diet-induced cholesterol accumulation in the liver and blood. J Lipid Res. 2012;53(6):1144-1152.

Nguyen TM, Sawyer JK, Kelley KL, Davis MA, Kent CR, Rudel LL. ACAT2 and ABCG5/G8 are both required for efficient cholesterol absorption in mice: evidence from thoracic lymph duct cannulation. J Lipid Res. 2012;53(8):1598-1609.

Jorgensen MJ, Rudel LL, Kavanagh K, Jasinska AJ, Freimer NB, Jentsch JD, Fairbanks LA, Fallon MT, Kaplan JR. The vervet research colony as a biomedical resource [abstract]. Am J Primatol. 2012;74(Suppl 1):68.

Jorgensen MJ, Rudel LL, Nudy M, Kaplan JR, Clarkson TB, Pajewski NM, Schnatz PF. 25(OH)D3 and cardiovascular risk factors in female nonhuman primates. J Womens Health. 2012;21(9):959-965.

Brown JM, Martinez K, Betters J, Shores N, Rudel LL, McIntosh MK, Thomas G. Regulation of the alpha beta hydrolase domain (ABHD) protein family in murine and human obesity [abstract]. FASEB J. 2012;26():597.4.

Shores NJ, Fernandez AZ, Tam NC, DAvis M, Wilson M, Sawyer JK, Rudel L. Hepatic cholesterol ester--not free cholesterol--is associated with steatohepatitis (NASH) in human beings [abstract]. Hepatology. 2012;56(Suppl 1):845A.

Medina MW, Gao F, Naidoo D, Rudel LL, Temel RE, McDaniel AL, Marshall SM, Krauss RM. Coordinately regulated alternative splicing of genes involved in cholesterol biosynthesis and uptake. PLoS ONE. 2011;6(4):e19420.

Sun H, Hu Y, Gu Z, Wilson MD, Chen YQ, Rudel LL, Willingham MC, Edwards IJ. Endogenous synthesis of n-3 polyunsaturated fatty acids in fat-1 mice is associated with increased mammary gland and liver syndecan-1. PLoS ONE. 2011;6(5):e20502.

Ohshiro T, Matsuda D, Sakai K, Degirolamo C, Yagyu H, Rudel LL, Omura S, Ishibashi S, Tomoda H. Pyripyropene A, an acyl-coenzyme A:cholesterol acyltransferase 2-selective inhibitor, attenuates hypercholesterolemia and atherosclerosis in murine models of hyperlipidemia. Arterioscler Thromb Vasc Biol. 2011;31(5):1108-1115.

Shores NJ, Link K, Fernandez A, Geisinger KR, Davis M, Nguyen T, Sawyer J, Rudel L. Non-contrasted computed tomography for the accurate measurement of liver steatosis in obese patients. Dig Dis Sci. 2011;56(7):2145-2151.

Voruganti V, Jorgensen MJ, Kaplan JR, Kauanagh K [sic] [Kavanagh K], Rudel LL, Temel R, Fairbanks LA, Comuzzie AG. Significant genotype by diet (GXD) interaction effects on cardiometabolic responses to a pedigree-wide, dietary challenge in Vervet monkeys (Chlorocebus aethiops sabaeus) [abstract]. Am J Primatol. 2011;73(Suppl 1):84.

Jorgensen MJ, Schnatz PF, Rudel LL, Nudy M, Kaplan JR, Clarkson TB. Low plasma concentrations of vitamin D3 are associated with increased cardiovascular risk factors in a female nonhuman primate model [abstract]. Menopause. 2011;18(12):1345.

Pedrelli M, Davoodpour P, Degirolamo C, Gomaraschi M, Larsson L, Rudel LL, Calabresi L, Gustafsson JA, Steffensen K, Eriksson M, Parini P. The inhibition of hepatic acyl coenzyme A:cholesterol acyltransferase (ACAT) 2 positively affects HDL metabolism and functionality in mice [abstract]. Atheroscler Suppl. 2011;12(1):39.

Brown JM, Chung S, Sawyer JK, Degirolamo C, Alger HM, Zhu X, Brown AL, Shah R, Davis MA, Kelley K, Wilson MD, Parks JS, Rudell LL, et al. Combined therapy of dietary fish oil and stearoyl-CoA desaturase 1 inhibition prevents the metabolic syndrome and atherosclerosis. Arterioscler Thromb Vasc Biol. 2010;30(1):24-30.

Chung S, Timmins JM, Duong M, Degirolamo C, Rong S, Sawyer JK, Singaraja RR, Rudel LL, Shelness GS, Parks JS, et al. Targeted deletion of hepatocyte ABCA1 leads to very low density lipoprotein triglyceride overproduction and low density lipoprotein hypercatabolism. J Biol Chem. 2010;285(16):12197-209.

Alger HM, Brown JM, Sawyer JK, Kelley KL, Shah R, Wilson MD, Willingham MC, Rudel LL. Inhibition of acyl-coenzyme A:cholesterol acyltransferase 2 (ACAT2) prevents dietary cholesterol-associated steatosis by enhancing hepatic triglyceride mobilization. J Biol Chem. 2010;285(19):14267-74.


Kavanagh K, Sajadian S, Jenkins KA, Wilson MD, Carr JJ, Wagner JD, Rudel LL. Neonatal and fetal exposure to trans-fatty acids retards early growth and adiposity while adversely affecting glucose in mice. Nutr Res. 2010;30(6):418-426.

Degirolamo C, Kelley KL, Wilson MD, Rudel LL. Dietary n-3 LCPUFA from fish oil but not alpha-linolenic acid-derived LCPUFA confers atheroprotection in mice. J Lipid Res. 2010;51(7):1897-1905.

Temel RE, Sawyer JK, Yu L, Lord C, Degirolamo C, McDaniel A, Marshall S, Wang N, Shah R, Rudel LL, Brown JM. Biliary sterol secretion is not required for macrophage reverse cholesterol transport. Cell Metab. 2010;12(1):96-102.

Madenspacher JH, Draper DW, Smoak KA, Li H, Griffiths GL, Suratt BT, Wilson MD, Rudel LL, Fessler MB. Dyslipidemia induces opposing effects on intrapulmonary and extrapulmonary host defense through divergent TLR response phenotypes. J Immunol. 2010;185(3):1660-1669.

Degirolamo C, Rudel LL. Dietary monounsaturated fatty acids appear not to provide cardioprotection. Curr Atheroscler Rep. 2010;12(6):391-396.

Degirolamo C, Kelley KL, Wilson MD, Rudel LL. Dietary omega-3 fatty acids shift plasma and hepatic lipid metabolism in a mouse model of atherosclerosis within the first day of treatment [abstract]. Arterioscler Thromb Vasc Biol. 2010;30(11):e248.

Nguyen TM, Sawyer JK, Kelley KL, Davis MA, Rudel LL. Acyl-CoA cholesterol:Acyl transferase 2 (ACAT2) promotes intestinal cholesterol absorption as measured by thoracic lymph duct cannulation [abstract]. Arterioscler Thromb Vasc Biol. 2010;30(11):e197.

Pedrelli M, Davoodpour P, Degirolamo C, Gomaraschi M, Larsson L, Rudel LL, Calabresi L, Gustafsson JA, Steffensen K, Eriksson M, et al. HDL metabolism and hepatic acyl coenzyme A: cholesterol acyltransferase (ACAT) 2 inhibition in mice [abstract]. Arterioscler Thromb Vasc Biol. 2010;30(11):e191.

Shores NJ, Fernandez AZ, Geisinger KR, Davis M, Nguyen T, Sawyer JK, Rudel LL. Non-contrasted computed tomography accurately estimates chemically measured hepatic steatosis in bariatric patients [abstract]. Hepatology. 2010;52(4 Suppl):649A-650A.

Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F. Omega-6 fatty acids and risk for cardiovascular disease: a science advisory from the American Heart Association Nutrition Subcommittee of the Council on Nutrition, Physical Activity, and Metabolism;. Circulation. 2009;119(6):902-907.

Degirolamo C, Shelness GS, Rudel LL. LDL cholesteryl oleate as a predictor for atherosclerosis: evidence from human and animal studies on dietary fat. J Lipid Res. 2009;50(Suppl):S434-S439.

Sacks FM, Rudel LL, Conner A, Akeefe H, Kostner G, Baki T, Rothblat G, de la Llera-Moya M, Asztalos B, Perlman T, et al. Selective delipidation of plasma HDL enhances reverse cholesterol transport in vivo. J Lipid Res. 2009;50(5):894-907.

Ohshiro T, Matsuda D, Nagai K, Doi T, Sunazuka T, Takahashi T, Rudel LL, Omura S, Tomoda H. The selectivity of beauveriolide derivatives in inhibition toward the two isozymes of Acyl-CoA: cholesterol acyltransferase. Chem Pharm Bull (Tokyo). 2009;57(4):377-381.

Temel RE, Brown JM, Ma Y, Tang W, Rudel LL, Ioannou YA, Davies JP, Yu L. Diosgenin stimulation of fecal cholesterol excretion in mice is not NPC1L1 dependent. J Lipid Res. 2009;50(5):915-923.

Pramfalk C, Karlsson E, Groop L, Rudel LL, Angelin B, Eriksson M, Parini P. Control of ACAT2 liver expression by HNF4alpha: lesson from MODY1 patients. Arterioscler Thromb Vasc Biol. 2009;29(8):1235-1241.

Fessler MB, Rudel LL, Brown JM. Toll-like receptor signaling links dietary fatty acids to the metabolic syndrome. Curr Opin Lipidol. 2009;20(5):379-385.

Parini P, Eriksson M, Rudel LL. Carotid atherosclerosis progression and ACAT inhibition [letter]. JAMA. 2009;302(3):255.

Chung S, Timmins JM, Duong M, Rong S, Sawyer JK, Maeda N, Rudel LL, Shelness GS, Parks JS. Targeted deletion of hepatocyte ABCA1 induces futile cycling of VLDL production and clearance in C57BL/6 mice [abstract]. Arterioscler Thromb Vasc Biol. 2009;29(7):e36.

Degirolamo C, Kelley KL, Rudel LL. Alpha linolenic acid-derived n-3 long-chain PUFAs are not as effective in atheroprotection as dietary PUFAs from fish oil despite similar plasma and hepatic enrichments in n-3 PUFAs [abstract]. Arterioscler Thromb Vasc Biol. 2009;29(7):e68.

McDaniel AL, Lan T, Marshall SM, Boyd CA, Kelley KL, Wilson MD, Sawyer JK, Rudel LL, Temel RE. Dietary n-3 fatty acids have minimal effects on intestinal Niemann-Pick C1 like 1 expression and cholesterol absorption [abstract]. Arterioscler Thromb Vasc Biol. 2009;29(7):e30.

Nguyen TM, Sawyer JK, Rudel LL. Cholesterol esterification by Acyl-CoA cholesterol:acyl transferase 2 increases intestinal sterol absorption efficiency [abstract]. Arterioscler Thromb Vasc Biol. 2009;29(7):e36.

Kavanagh K, Davis MA, Zhang L, Wilson MD, Register TC, Adams MR, Rudel LL, Wagner JD. Estrogen decreases atherosclerosis in part by reducing hepatic acyl-CoA: cholesterol acyltransferase 2 (ACAT2) in monkeys. Arterioscler Thromb Vasc Biol. 2009;29(10):1471-1477.

Brown WV, Karmally W, Kris-Etherton P, Rudel LR [sic] [Rudel LL]. Discussion on dietary fat [roundtable discussion]. J Clin Lipidol. 2009;3(5):303-314.

Parini P, Jiang Z-Y, Einarsson C, Eggertsen G, Zhang S-D, Rudel LL, Han T-Q, Eriksson M. ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences in normolipidemic, non-obese Chinese patients. Atherosclerosis. 2009;207(1):266-271.

Zhou M, Sawyer J, Kelley K, Fordstrom P, Chan J, Tonn G, Carlson T, Retter M, Meininger D, Rudel L, et al. Lecithin cholesterol acyltransferase promotes reverse cholesterol transport and attenuates atherosclerosis progression in New Zealand white rabbits [abstract]. Circulation. 2009;120(18 Suppl 2):S1175.

Degirolamo C, Rudel L, Bell T III. Dietary unsaturated fatty acids are unique in effectiveness in atheroprotection [abstract]. Atheroscler Suppl. 2009;10(2):Abstr 53.

Chilton FH, Rudel LL, Parks JS, Arm JP, Seeds MC. Mechanisms by which botanical lipids affect inflammatory disorders. Am J Clin Nutr. 2008;87(2 Suppl):498S-503S.

Jiang Z-Y, Parini P, Eggertsen G, Davis MA, Hu H, Suo G-J, Zhang S-D, Rudel LL, Han T-Q, Einarsson C. Increased expression of LXR alpha, ABCG5, ABCG8, and SR-BI in the liver from normolipidemic, nonobese Chinese gallstone patients. J Lipid Res. 2008;49(2):464-472.

Brown JM, Bell TA III, Alger HM, Sawyer JK, Smith TL, Kelley K, Shah R, Wilson MD, Davis MA, Rudel LL, et al. Targeted depletion of hepatic ACAT2-driven cholesterol esterification reveals a non-biliary route for fecal neutral sterol loss. J Biol Chem. 2008;283(16):10522-34.


Alger HM, Temel RE, Kelley KL, Wilson MD, Sawyer JK, Shah R, Rudel LL. ATP-binding cassette transporter G5/G8 prevents accumulation of toxic levels of phytosterols in dietary phytosterol-challenged mice [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):E58.

Brown JM, Chung S, Alger HM, Sawyer JK, Degirolamo C, Nguyen T, Zhu X, Duong M-N, Wibley AL, Davis MA, Kelley K, Wilson MD, Parks JS, Rudel LL. Inhibition of stearoyl-CoA desaturase 1 (SCD1) dissociates insulin resistance and obesity from atherosclerosis [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):e-93.

Chung S, Timmins J, Duong M, Seo J, Gebre A, Boudyguina E, Shah R, Sawyer J, Rudel L, Shelness G, Parks JS, et al. Hepatic-specific deletion of ABCA1 promotes PI3 kinase-dependent VLDL maturation: a novel role for ABCA1 in the regulation of VLDL triglyceride assembly [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):e-93-e-94.

Degirolamo C, Kelley KL, Rudel LL. Dietary flaxseed oil compared to monounsaturated fat limits hepatic cholesteryl ester deposition in a mouse model of atherosclerosis [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):e-60.

Iqbal J, Rudel LL, Hussain MM. Microsomal triglyceride transfer protein enhances cellular cholesterol esterification by relieving product inhibition [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):e-129.

Parini P, Gustafsson U, Davis MA, Larsson L, Einarsson C, Wilson M, Rudling M, Tomoda H, Omura S, Sahlin S, Angelin B, Rudel LL, Eriksson M. Cholesterol synthesis inhibition elicits an integrated molecular response in human livers including decreased ACAT2. Arterioscler Thromb Vasc Biol. 2008;28(6):1200-1206.

Temel RE, Alger HM, Marshall SM, Boyd CA, Kelley KL, Wilson MD, Sawyer JK, Gebre AK, Parks JS, Rudel LL. Mice lacking ABCA1 and ACAT2 have surface-rich, core-depleted LDL due to LCAT deficiency [abstract]. Arterioscler Thromb Vasc Biol. 2008;28(6):e-133.

Edwards IJ, Sun H, Hu Y, Berquin IM, O'Flaherty JT, Cline JM, Rudel LL, Chen YQ. In vivo and in vitro regulation of syndecan 1 in prostate cells by n-3 polyunsaturated fatty acids. J Biol Chem. 2008;283(26):18441-9.

Das A, Davis MA, Rudel LL. Identification of putative active site residues of ACAT enzymes. J Lipid Res. 2008;49(8):1770-1781.


Brown JM, Chung S, Sawyer JK, Degirolamo C, Alger HM, Zhu X, Duong M-N, Wibley AL, Shah R, Davis MA, Kelley K, Wilson MD, Kent C, Parks JS, Rudel LL, et al. Inhibition of stearoyl-coenzyme A desaturase 1 dissociates insulin resistance and obesity from atherosclerosis. Circulation. 2008;118(14):1467-1475.

Matsuda D, Ohte S, Ohshiro T, Jiang W, Rudel L, Hong B, Si SY, Tomada H. Molecular target of piperine in the inhibition of lipid droplet accumulation in macrophages. Biol Pharm Bull. 2008;31(6):1063-1066.

Ohshiro T, Ohte S, Matsuda D, Ohtawa M, Nagamitsu T, Sunazuka T, Harigaya Y, Rudel LL, Omura S, Tomoda H. Selectivity of pyripyropene derivatives in inhibition toward acyl-CoA : cholesterol acyltransferase 2 isozyme. J Antibiot. 2008;61(8):503-508.

Sakai K, Ohte S, Ohshiro T, Matsuda D, Masuma R, Rudel LL, Tomoda H. Selective inhibition of acyl-CoA : cholesterol acyltransferase 2 isozyme by flavasperone and sterigmatocystin from Aspergillus species. J Antibiot. 2008;61(9):568-572.

Otvos JD, Rudel LL, McConnell JP. Concerns regarding lipoprotein particle measurement by ion mobility analysis [letter]. Clin Chem. 2008;54(12):2086-2087.

Chung S, Timmins JM, Duong M, Seo J, Gebre A, Boudyguina E, Rudel LL, Shelness G, Shah R, Sawyer J, Parks JS, et al. A novel role for Abca1-generated large nascent HDL in the regulation of VLDL triglyceride secretion [abstract]. Circulation. 2008;118(18 Suppl 2):S558.

Ohshiro T, Rudel LL, Omura S, Tomoda H. Selectivity of microbial acyl-CoA: cholesterol acyltransferase inhibitors toward isozymes. J Antibiot. 2007;60(1):43-51.

Brown JM, Lemonidis KM, Graham MJ, Crooke RM, Rudel L. Probing the role of hepatic cholesterol esterification in atherosclerosis promotion via liver-specific depletion of ACAT2 [abstract]. FASEB J. 2007;21(5 Pt I):A109.

Das A, Davis MA, Rudel LL. PyripyropeneA (PPPA) specifically inhibits acyl coenzyme A (CoA):cholesterol acyltransferase-2(ACAT2) by interacting with the enzyme near its C-terminal end [abstract]. FASEB J. 2007;21(5 Pt I):A607.

Bell TA III, Kelley K, Wilson MD, Sawyer JK, Rudel LL. Dietary fat-induced alterations in atherosclerosis are abolished by ACAT2-deficiency in ApoB100 only, LDLr-/- mice. Arterioscler Thromb Vasc Biol. 2007;27(6):1396-1402.

Bell TA III, Wilson MD, Kelley K, Sawyer JK, Rudel LL. Monounsaturated fatty acyl-coenzyme A is predictive of atherosclerosis in human apoB-100 transgenic, LDLr-/- mice. J Lipid Res. 2007;48(5):1122-1131.

Alger HM, Parini P, Shah R, Yu L, Rudel LL. Acyl-Coa:cholesterol acyltransferase 2 and ATP-binding cassette half transporters G5 and G8 differentially alter hepatic lipoprotein secretion and composition [abstract]. Arterioscler Thromb Vasc Biol. 2007;27(6):e-57.

Jiang Z-Y, Einarsson C, Eggertsen G, Davis MA, Wang L, Zhang S-D, Eriksson M, Han T-Q, Rudel LL, Parini P. ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences [abstract]. Arterioscler Thromb Vasc Biol. 2007;27(6):e-92.

Parini P, Davis M, Sahlin S, Angelin B, Rudel LL, Eriksson M. Reduced hepatic ACAT2 activity is part of the integrated response to inhibition of cholesterol synthesis in humans [abstract]. Arterioscler Thromb Vasc Biol. 2007;27(6):e-61.

Jiang ZY, Parini P, Einarsson C, Eggertsen G, Davis MA, Wang L, Zhang SD, Rudel LL, Han TQ, Ericsson M. ACAT2 and human hepatic cholesterol metabolism: identification of important gender-related differences [abstract]. Atheroscler Suppl. 2007;8(1):24.

Parini P, Gustafsson U, Einarsson C, Shalin S, Rudling M, Angelin B, Rudel LL, Eriksson M. Reduction of ACAT2 is an important effect of cholesterol synthesis inhibition in human livers [abstract]. Atheroscler Suppl. 2007;8(1):21.

Pramfalk C, Karlsson E, Eriksson M, Angelin B, Groop L, Rudel LL, Parini P. HNF4 alpha is essential for ACAT2 regulation in human: lesson from the MODY patients [abstract]. Atheroscler Suppl. 2007;8(1):43.

Sacks FM, Rudel L, Asztalos BF, Zheng CY, Conner A, Akeefe H, Perlman T, Maltais J, Rothblat GH, Brewer HB. Selective delipidation of HDL in plasma produces pre-beta HDL effective in reverse cholesterol transport in vivo in monkeys [abstract]. Atheroscler Suppl. 2007;8(1):228.

Temel RE, Tang W, Ma Y, Rudel LL, Willingham MC, Ioannou YA, Davies JP, Nilsson L-M, Yu L. Hepatic Niemann-Pick C1-like 1 regulates biliary cholesterol concentration and is a target of ezetimibe. J Clin Invest. 2007;117(7):1968-1978.

Kavanagh K, Jones KL, Sawyer J, Kelley K, Carr JJ, Wagner JD, Rudel LL. Trans fat diet induces abdominal obesity and changes in insulin sensitivity in monkeys. Obesity. 2007;15(7):1675-1684.

Kavanagh K, Fairbanks LA, Bailey JN, Jorgensen MJ, Wilson M, Zhang L, Rudel LL, Wagner JD. Characterization and heritability of obesity and associated risk factors in vervet monkeys. Obesity. 2007;15(7):1666-1674.

Temel RE, Hou L, Rudel LL, Shelness GS. ACAT2 stimulates cholesteryl ester secretion in apoB-containing lipoproteins. J Lipid Res. 2007;48(7):1618-1627.

Brown JM, Chung S, Das A, Shelness GS, Rudel LL, Yu L. CGI-58 facilitates the mobilization of cytoplasmic triglyceride for lipoprotein secretion in hepatoma cells. J Lipid Res. 2007;48(10):2295-2305.


Zhao B, Song J, Chow WN, St. Clair RW, Rudel LL, Ghosh S. Macrophage-specific transgenic expression of cholesteryl ester hydrolase significantly reduces atherosclerosis and lesion necrosis in Ldlr-/- mice. J Clin Invest. 2007;117(10):2983-2992.

Temel RE, Rudel LL. Diet effects on atherosclerosis in mice. Curr Drug Targets. 2007;8(11):1150-1160.

Brown JM, Shelness GS, Rudel LL. Monounsaturated fatty acids and atherosclerosis: opposing views from epidemiology and experimental animal models. Curr Atheroscler Rep. 2007;9(6):494-500.


Ohshiro T, Namatame I, Nagai K, Sekiguchi T, Doi T, Takahashi T, Akasaka K, Rudel LL, Tomoda H, Omura S. Absolute stereochemistry of fungal beauveriolide III and ACAT inhibitory activity of four stereoisomers. J Org Chem. 2006;71(20):7643-7649.

Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, Franklin B, Kris-Etherton P, Harris WS, Rudel L, et al. Summary of American Heart Association Diet and Lifestyle Recommendations Revision 2006 [editorial]. Arterioscler Thromb Vasc Biol. 2006;26(10):2186-2191.

Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, Franklin B, Kris-Etherton P, Harris WS, Rudel L, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006;114(1):82-96.

All Publications

For a listing of recent publications, refer to PubMed, a service provided by the National Library of Medicine.

For a list of earlier publications, visit the Carpenter Library Publication Search.

Lawrence L. Rudel, Ph.D.

Lawrence L. Rudel, Ph.D.

Professor, Molecular Medicine
WFU Primate Center
Biochemistry
Translational Science Institute

Contact Information

Academic: 336-716-2823 | Department: 336-716-2823

Email: lrudel@wakehealth.edu

Current Research:

Cholesterol Metabolism, Lipoproteins, Primates

Complications arising from coronary heart disease are the number one cause of death in our country. Atherosclerosis is the underlying disease process. We have developed nonhuman primate (monkey) models of diet-induced coronary artery atherosclerosis (CAA). We are attempting to define molecular mechanisms through which dietary fatty acids modify plasma lipoprotein distribution and composition and their respective roles in CAA. Increased blood plasma concentrations of low density lipoproteins (LDL) and decreased concentrations of high density lipoproteins (HDL) both contribute to increased CHD in man and monkeys.

Pathways regulating plasma lipoprotein concentrations are under study. In addition, increased LDL cholesteryl oleate content has been associated with increased CAA. Isolated, perfused primate livers have been used to demonstrate that hepatic cholesteryl oleate secretion rate is correlated with LDL cholesteryl oleate enrichment and increased CAA. The enzyme in the liver responsible for cholesteryl oleate formation and secretion has been identified as acyl-CoA:cholesterol acyltransferase 2 (ACAT2). This enzyme has been cloned, expressed, and regulation by cholesterol and fatty acids is under investigation. Intrahepatic metabolism of cholesterol determines the type and extent of lipoprotein particle secretion by the liver, so we are quantifying entry and exit pathways for cholesterol in the liver. To accomplish this, we are examining transcriptional regulation of the genes controling hepatic cholesterol metabolism, particularly ACAT2 and cholesterol 7-a-hydroxylase, as this regulation is influenced by cholesterol and fatty acid type.

In sum, by delineating molecular aspects of diet responsiveness of cholesterol and lipoprotein metabolism in a nonhuman primate model of CAA, we are providing information that can eventually be helpful in development of strategies for prevention of coronary heart disease.

LL Rudel: Figure 1

Figure 1: The role of ACAT1 and ACAT2 in cholesterol metabolism

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