Willem J.S. de Villiers, M.D., Ph.D.
Chief of the Division of Digestive Diseases and Nutrition
Associate Professor of Internal Medicine
Department of Medicine, Digestive Diseases and Nutrition

MN 649 Medical Center
Lexington, KY 40506-0084
Tel: (859) 323-4887
Fax: (859) 257-8860
e-mail: willem.devilliers@uky.edu

Education:

• M.D., Internal Medicine, University of Stellenbosch, South Africa, 1991
• Ph.D., Macrophage Biology, University of Oxford, England, 1995

Specific interest in nutrition:

The role of macrophage pattern recognition and scavenger receptors in chronic inflammation in inflammatory bowel disease and atherosclerosis.

Research:

Dr. de Villiers' current research interests and projects include macrophage scavenger and pattern recognition receptors (SR-A, CD36, SR-B1, TLRs) --regulation of expression and activity and their role in various models of chronic inflammation. He is also pursuing the the role of lamina propria macrophages, their scavenger receptors and NO production in inflammatory bowel disease (IBD) using various genetically engineered mouse models of IBD, such as IL-10 deficient mice; and phenotype characterization of macrophage scavenger receptor-deficient mice--susceptibility to atherosclerosis, alcohol, and colitis. Finally, Dr. de Villiers is concentrating on secretory phospholipase A2 (sPLA2): gut production and role in IBD.

Publications (selected from 52 peer-reviewed):

De Villiers WJS , Fraser IP, Hughes DA, Doyle AG, Gordon S. M-CSF selectively enhances scavenger receptor expression and function in murine macrophages. J Exp Med 1994; 180: 705-709.

De Villiers WJS , Fraser IP, Gordon S. Cytokine and growth factor regulation of macrophage scavenger receptor expression and function. Immunology Letters 1994; 43: 73-79.

De Villiers WJS , van der Westhuyzen DR, Coetzee GA, Henderson HE, Marais AD. The apolipoprotein E145 (Cys to Arg) mutation causes autosomal dominant type III hyperlipoproteinemia with delayed penetrance. Arterioscler Thromb Vasc Biol 1997; 17: 865-872.

Webb NR, de Villiers WJS, Connell PM, de Beer FC, van der Westhuyzen DR. Alternative forms of the scavenger receptor BI (SR-BI). J Lipid Res 1997; 38: 1490-1495.

Welch CL, Xia Y-R, Gu LJ, Machleder D, Mehrabian M, Wen P-Z, Webb N, de Villiers WJS, van der Westhuyzen DR, Lusis AJ. Srb1 maps to mouse chromosome 5 in a region harboring putative QTLs for plasma lipoprotein levels. MammalianGenome 1997; 8: 942-944.

De Villiers WJS , Smith JD, Miyata M, Dansky HM, Darley E, Gordon S. Macrophage phenotype in mice deficient in both macrophage-colony stimulating factor (op) and apolipoprotein E. Arterioscler Thromb Vasc Biol 1998; 18: 631-640.

Webb NR, Connell PM, Graf GA, Smart EJ, de Villiers WJS, de Beer FC, van der Westhuyzen DR. SR-BII, an isoform of the scavenger receptor BI containing an alternate cytoplasmic tail, mediates lipid transfer between high density lipoprotein and cells. J Biol Chem 1998; 273: 15241-15248.

Jiang Z, Shih DM, Xia Y-R, Lusis AJ, de Beer FC, de Villiers WJS, van der Westhuyzen DR, de Beer, MC. Structure, Organization, and Chromosomal Mapping of the Macrosialin Gene, a Macrophage-restricted Protein. Genomics 1998; 50: 199-205.

Yang F, de Villiers WJS, McClain CJ, Varilek GW. Green tea polyphenols block LPS-induced TNF- production and lethality in a murine model. J Nutrition 1998; 128: 2334-2340.

Yang F, Lee E, de Villiers WJS, McClain CJ, Varilek GW. Nuclear factor-kappa B is increased in colitis of IL-2 deficient mice. J Lab Clin Med 1999; 134: 378-385.

De Villiers, WJS , Smart, EJ. Macrophage scavenger receptors and foam cell formation. J Leukoc Biol 1999; 66: 740-746.

Hamilton, RF, de Villiers WJS, Holian A. Class A type II scavenger receptor mediates silica-induced apoptosis in Chinese hamster ovary cells. Toxicol Appl Pharmacol 2000; 162: 100-106.


De Villiers WJS , Varilek GW, de Beer FC, Kindy MS. Chronically elevated serum amyloid A and serum amyloid P levels cause systemic amyloid deposition in IL-2 knockout mice. Cytokine 2000; 12: 1337-1347.

Deaciuc IV, D’Souza NB, de Villiers WJS, Burikhanov R, Sarphie TG, Hill DB, McClain CJ. Inhibition of caspases in vivo protects the rat liver against alcohol-induced sensitization to bacterial lipopolysaccharide. Alcohol Clin Exp Res 2001; 25: 935-43.

Varilek GW, Yang F, Lee EY, de Villiers WJS, Zhong J, Westberry KF, McClain CJ. Green tea polyphenol extract attenuates inflammation in interleukin-2-deficient mice, a model of autoimmunity. J Nutrition 2001; 131: 2034-2039.

De Villiers WJS , Cai L, Webb NR, de Beer MC, van der Westhuyzen DR, de Beer FC. CD36 does not play a direct role in HDL or LDL metabolism. J Lipid Res 2001; 42: 1231-1238.

Yang F, Oz H, Barve S, de Villiers WJS, McClain CJ, Varilek GW. The green tea polyphenol, (-)-epigallocatechin-3-gallate blocks nuclear factor-kappa B activation by inhibiting I-kappa B kinase activity. Mol Pharmacol 2001; 60: 528-533.

Hill DB, D’Souza NB, Lee EY, Burikhanov R, Deaciuc IV, de Villiers WJS. A role for interleukin-10 in alcohol-induced liver sensitization to bacterial lipopolysaccharide. Alcohol Clin Exp Res 2002; 26: 74-82.

Gaetke LM, Oz HS, de Villiers WJS, Varilek GW, Frederich RC. The leptin defense against wasting is abolished in the IL-2 deficient model of inflammatory bowel disease. J Nutrition 2002; 132: 893-896.

Deaciuc IV, D’Souza NB, Burikhanov R, Lee EY, Tarba CN, McClain CJ, de Villiers WJS. Epidermal growth factor protects the liver against alcohol-induced injury and sensitization to bacterial lipopolysaccharide. Alcohol Clin Exp Res 2002, 26: 864-874.

Deaciuc IV, D’Souza NB, Nikolova-Karakashian M, de Villiers WJS, Sarphie TG, Hill DB, McClain CJ. The regulation of Fas (CD95/Apo-1)-mediated liver apoptosis in Kupffer cell-depleted mice. Hepatol Res 2002; 24: 192-204.

De Beer MC, Zhao Z, Webb NR, van der Westhuyzen DR, de Villiers WJS . Lack of a direct role for macrosialin in oxidized LDL metabolism . J Lipid Res 2003; 44: 674-685.

De Villiers WJS . Crohn’s disease and IL-10 therapy: Promise regained? Inflamm Bowel Dis 2003; 9: 210-211.

De Villiers WJS , van der Westhuyzen DR. Macrophage lipid uptake and foam cell formation. Handbook of Experimental Pharmacology 2003; 158: 147-172.

Cai L, Eckhardt ERM, Shi W, Zhao Z, Nasser M, de Villiers WJS, van der Westhuyzen DR. Scavenger receptor class B type I reduces cholesterol absorption in cultured enterocyte CaCo-2 cells. J Lipid Res 2004; 45: 253-262. Epub 2003 Nov 16.

Deaciuc IV, Doherty DE, Burikhanov R, Lee EY, Stromberg AJ, Peng X, de Villiers WJS. Large scale hepatic gene profiling in a mouse model of chronic, intragastric ethanol infusion. J Hepatology 2004; 40: 219-227.

Deaciuc IV, D’Souza NB, Burikhanov R, Nasser MS, Voskresensky IV, de Villiers WJS, McClain CJ. Alcohol- but not lipopolysaccharide-induced liver apoptosis involves changes in intracellular compartmentalization of apoptotic regulators. Alcohol Clin Exp Res 2004; 28: 160-172.

Wooton-Kee CR, Boyanovsky BB, Nasser MS, de Villiers WJS, Webb NR. Group V sPLA 2 hydrolysis of LDL results in spontaneous particle aggregation and promotes macrophage foam cell formation. Arterioscler Thromb Vasc Biol 2004, 24: 762-767 (Epub Feb 12).

Chelvarajan RL, Doubinskaia IE, Goes S, van Willigen J, Lowery D, de Villiers WJS, Bryson JS, Bondada S. Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens. J Leuk Biol 2004, 75: 982-994 (Epub Feb 24).

Sands, BE, Anderson FH, Bernstein CN, Chey W, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken J, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters P, Travers S, Blank M, van Deventer SJ and the ACCENT II Study Group. A randomized controlled trial of infliximab maintenance therapy for fistulizing Crohn’s disease (ACCENT II). N Engl J Med 2004; 350: 876-885.

Deaciuc IV, Peng X, Burikhanov R, D’Souza NB, Shedlofsky SI, Voskresensky IV, de Villiers WJS. Microarray gene analysis of the liver in a rat model of chronic, voluntary alcohol intake. Alcohol 2004; 32: 113-127.

Selby LA, Hess D, Shashidar H, de Villiers WJS. Crohn’s disease, infliximab and idiopathic thrombocytopenic purpura. Inflamm Bowel Dis 2004; 10: 698-700.

Mardini HE, de Villiers WJS. To (I)B(D) or NOD2 (I)B(D) – Are Paneth cells the answer? Inflamm Bowel Dis 2004; 10: 696-697.

Sandborn WJ, Feagan BG, Radford-Smith G, Kovacs A, Enns R, Innes A, Patel J and the CDP571 Investigator Group. CDP571, a humanized monoclonal antibody to tumour necrosis factor , for moderate to severe Crohn’s disease: a randomized, double blind, placebo controlled trial. Gut 2004; 53: 1485-1493.

Selby LA, de Castro F, de Villiers WJS. The association of bullous pemphigoid and ulcerative colitis. Dig Dis Sci 2004; 49: 1768-1770.

Zhao Z, de Beer MC, Cai L, Asmis R, de Beer FC, de Villiers WJS, van der Westhuyzen DR.Low-density lipoprotein from apolipoprotein E-deficient mice induces macrophage lipid accumulation in a CD36 and scavenger receptor class A-dependent manner. Arterioscler Thromb Vasc Biol 2005; 25: 168-173 (Epub Oct 28).

Oz HS, McClain CJ, Nagasawa HT, Ray MB, de Villiers WJS, Chen TS. Diverse antioxidants protect against acetaminophen hepatotoxicity. J Biochem Molecular Toxicology 2004; 18: 361-368 (Epub Jan 26, 2005).

Oz HS, Chen T, de Villiers WJS, McClain CJ. Metallothionein overexpression does not protect against inflammatory bowel disease in a murine colitis model. Med Sci Monit 2005, 11: 69-73.


Oz HS, Chen T, McClain CJ, de Villiers WJS. Antioxidants as novel therapy in a murine model of colitis. J Nutr Biochem 2005; 16: 297-304.

Mardini HE, de Villiers WJS. Clostridium difficile-associated diarrhea in long-term care facilities. Long-Term Care Interface 2005; 6 (3): 48-54.

Chang PK , Holt EG, de Villiers WJS, Boulanger BR. A new complication from a new technology: What a general surgeon should know about wireless capsule endoscopy. Am Surg, 2005; 71: 455-458.

Mardini HE, Gregory K, Nasser MS, Selby L, Arsenescu R, Winter TA, de Villiers WJS. Gastroduodenal Crohn’s disease is associated with NOD2/CARD15 gene polymorphisms particularly L1007P homozygosity. (Dig Dis Sci, in press)