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  1. 1. Principal Investigator/Program Director (Last, First, Middle): BIOGRAPHICAL SKETCH Provide the following information for the key personnel and other significant contributors in the order listed on Form Page 2. Follow this format for each person. DO NOT EXCEED FOUR PAGES. NAME POSITION TITLE William M. Pandak, Jr., M.D. Professor of Medicine EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, and include postdoctoral training.) DEGREE INSTITUTION AND LOCATION (if YEAR(s) FIELD OF STUDY applicable) Randolph-Macon College, Ashland, VA B.S. 1978 Biology Virginia Commonwealth University, Richmond, M.D. 1983 Medicine VAA. POSITIONS AND HONORS: Positions and Employment1983 - 86 Residency in Internal Medicine, Virginia Commonwealth University, Richmond, VA1986 - 87 Clinical Gastroenterology Fellowship, Virginia Commonwealth University1987 - 88 National Institutes of Health Training Grant Fellowship, Virginia Commonwealth University1988- Staff Physician, Veterans Affairs Medical Center, Richmond, VA1988 - 89 Instructor of Clinical Medicine, Virginia Commonwealth University1989 - 94 Assistant Professor of Medicine, Virginia Commonwealth University1994 - 99 Associate Professor of Medicine, Virginia Commonwealth University1999 - Professor of Medicine, Virginia Commonwealth University Other Experience and Professional Memberships:American Heart Association; American College of Physicians; American Association for the Study of LiverDiseases; American Gastroenterology Association; American Medical Association; Editorial board Metabolism;Reviewer – American Journal of Physiology; Clinical Gastroenterology and Hepatology, Gastroenterology,Gene, Hepatology, Journal of Lipid Research, Lipids; Mammalian Gene; Grant Reviewer – Veterans AffairsMerit Review Awards; Director, Biliary Service, Veterans Affairs Medical Center, Fellowship training intherapeutic biliary endoscopy, 1990; Member, Clinical Competency Committee for Gastroenterology Fellows,1993; Member, Affiliate Graduate Faculty for Graduate Education in the School of Medicine, ABIM certified inInternal Medicine and Gastroenterology Honors:Omicron Delta Kappa - 1977; Phi Bet Kappa- 1978; American Liver Foundation Research Scholar Award –1988; Veterans Administration Career Development Awards – 1988 and 1992; Fellow in the American HeartAssociation – 1997; Fellow in the American College of Physicians – 2005; Fellow in the AmericanGastroenterologic Association - 2006.PHS 398/2590 (Rev. 09/04) Page Biographical Sketch Format Page
  2. 2. Principal Investigator/Program Director (Last, First, Middle):B. PEER-REVIEWED PUBLICATIONS: (Selected papers from more recent publications)1.Deal SE, Pandak WM, Heuman DM. Lack of Efficacy of Ketorolac Tromethamine for Analgesia on PatientsUndergoing Colonoscopy. The Amer. J. Gastro. 88:1050-1053, 1993.2.Ghosh S, Natarajan R, Pandak WM, Hylemon PB, and Grogan WM. Regulation of hepatic neutralcholesteryl ester hydrolase by hormones and changes in cholesterol flux. Am. J. of Physiology 274:G662-G668, 1998.3.Bhagway SV, Biswas G, Anadatheerthavarada HK, Addya S, Pandak WM, Avadhani NG. Dual targeting ofthe N-terminal signal sequence of P4501A1: targeting of heterologous proteins to endoplasmic reticulum andmitochondria. J. Biol. Chem. 274:2401-2422, 1999.4.Gupta S, Stravitz RT, Pandak WM, Muller M, Vlahcevic ZR, Hylemon PB. Regulation of MDR2 P-glycoprotein expression by bile salts in rats and in primary cultures of rat hepatocytes. Hepatology32:341-347, 2000.5.Vlahcevic ZR, Eggertsen G, Bjorkhem I, Hylemon PB, Redford K, Pandak WM. Regulation of sterol 12α-hydroxylase and cholic acid biosynthesis in the rat. Gastroenterology, 118:599-607, 2000.6.Hall EH, Hylemon PB, Vlahcevic ZR, Mallonee D, Valerie K, Avadhani NG, Pandak WM. Overexpression ofCYP27 in hepatic and extrahepatic cells: Its role in the regulation of cholesterol homeostasis. Am. J.Physiology 281:G293-G301, 2001.7.Pandak WM, Bohdan P, Franklund C, Mallonee DH, Eggertsen G, Bjorkhem I, Gil G, Vlahcevic ZR,Hylemon PB. Expression of sterol 12α-hydroxylase alters bile acid pool composition in primary rathepatocytes and in vivo. Gastroenterology 120:1801-1809, 2001.8.Pandak WM, Schwarz C, Hylemon PB, Mallonee D, Valerie K, Heuman DM, Fisher RA, Redford K,Vlahcevic ZR. Effects of CYP7A1 overexpression on cholesterol and bile acid homeostasis. Am. J. ofPhysiology 281:G878-889, 2001.9.Pandak WM, Arezo S, Everette S, Jesse R, DeCosta G, Crofts T, Gennings C, Suita M, and Zfass A: ShortCourse of Omeprazole: Better First Diagnostic Approach to Non Cardiac Chest Pain (NCCP) Than Endoscopy,Manometry, or 24 Hour Esophageal pH Monitoring. Journal of Clinical Gastroenterology. 2002.Oct;35(4):307-314, 2002.10.Pandak WM, Hylemon PB, Ren S, Marques D, Gil G, Redford K, Mallonee D, Vlahcevic ZR. Regulation ofoxysterol 7α-hydroxylase (CYP7B1) in primary cultures of rat hepatocytes. Hepatology, 35:1400-8, 2002.11.Gupta S, Pandak WM, Hylemon PB. LXRα is the dominant regulator of CYP7A1 transcription. Biochem.Biophys. Res. Commun. 293:338-343, 2002.12.Pandak WM, Ren S, Marques DM, Gil G, Redford K, Hall E, Heuman D, Hylemon PB. Transport ofcholesterol into mitochondria is rate limiting for bile acid synthesis via the alternative pathway in primary rathepatocytes. J. Biol. Chem. 277:48158-48164, 2002.13.Ren S, Marques D, Redford K, Hylemon PB, Gil, G, Vlahcevic ZR, Pandak WM. Regulation of oxysterol7α-hydroxylase (CYP7B1) in the rat. Metabolism 52:636-642, 2003.14.Williams K, Rao YP, Natarajan R, Pandak WM, Hylemon PB. Indinavir alters sterol and fatty acidhomeostatic mechanisms in primary rat hepatocytes by increasing levels of activated sterol regulatory elementbinding proteins and decreasing cholesterol 7α-hydroxylase mRNA levels. Biochemical Pharmacology67:255-267, 2004.15.Ren S, Hylemon PB, Marques D, Gurley EC, 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 andmouse. Hepatology 40:910-7, 2004.16.Ren S, Hylemon PB, Marques D, Hall E, Redford K, Gil G, Pandak WM. Effect of increasing theexpression of cholesterol transporters (StAR, MLN65, and SCP-2) on bile acid synthesis. J Lipid Research45:2123-31, 2004.17.del Castillo-Olivares A, Campos JA, Pandak WM, Gil G. The role of alpha-1fetoprotein transcriptionfactor/LRH-1 in bile acid biosynthesis: a known nuclear receptor activator that can act as a suppressor of bileacid biosynthesis. J Biol Chemistry 279:16813-21, 2004.PHS 398/2590 (Rev. 09/04) Page Continuation Format Page
  3. 3. Principal Investigator/Program Director (Last, First, Middle):18.Ren S, Hylemon PB, Marques D, Gurley E, Bodham P, Hall E, Redford K, Gil G, and Pandak WM.Overexpression of the Mitochondrial Cholesterol Transport Protein, StAR, Increases In Vivo Rates of Bile AcidSynthesis in the Rat and Mouse. Hepatology. 40:910-917, 2004.19.Ren, S., Hylemon, P.B., Marques, D., Hall, Redford, K., Gil, G., and Pandak, W.M. Effect of Increasingthe Expression of Cholesterol Transporters (StAR, MLN64, and SCP-2) on Bile Acid Synthesis. J. Lipid Res.2004 Nov;45(11):2123-31. Epub 2004 Sep 01.20.Hall EA, Ren S, Hylemon PB, Rodriguez-Agudo D, Redford K, Marques D, Kang D, Gil G, and PandakWM. Detection of the Steroidogenic Acute Regulatory Protein, StAR, in Human Liver Cells. Biochim BiophysActa. 2005 Apr 15;1733(2-3):111-9. Epub 2005 Mar 2.21.Rodriguez-Agudo D, Ren S, Hylemon PB, Redford K, Natarajan R, del Casillo A, Gil G, and Pandak WM.Human StarD5, a cytosolic Star-related Lipid Binding Protein. Journal of Lipid Research. 2005Aug;46(8):1615-23. Epub 2005 May 16.22.Sargramostim for Active Crohn’s Disease. Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF,Gilbert MJ, for the Sargramostim (Leukine) in Crohn’s Disease Study Group. Member WM Pandak. NewEngland Journal of Medicine. 2005. May 26;352(21):2193-201.23.Zhou H, Pandak WM, Lyall V, Natarajan R, and Hylemon PB. HIV Protease Inhibitors Activate theUnfolded Protein Response in Macrophages: Implication for Atherosclerosis and Cardiovascular Disease.Molecular Pharmacology. 2005 Sep;68(3):690-700. Epub 2005 Jul 8.24.Hall EA, Ren S, Hylemon PB, Redford K, del Castillo A, Gil G, and Pandak WM. Mitochondrial CholesterolTransport: A Possible Target in the Management of Hyperlipidemia. Lipids 2005. Dec;40:1237-1244. Paper no.L9848.25.Zhou H, Pandak WM, Hylemon PB. Cellular Mechanisms of Lipodystrophy by HIV Protease Inhibitors.Future Lipidology 2006. 1(2): 163-172. Online press.26.Ren S, Hylemon PB, Zhang ZP, Rodriguez-Agudo D, Hall EA, Marques D, Zhou H, Gil G, and PandakWM. Indentification of a Novel Sulfonated Oxysterol, 5-Cholesten-3β,25-diol 3-sulfonate in hepatocyte nucleiand mitochondria. Journal of Lipid Research. published February 27, 2006, doi:10.1194/jlr.M600019-JLR200Epub 2006 Feb.27.Rodriguez-Agudo D, Ren S, Hylemon PB, Medina MA, Montañez R, Redford K, Gil G, and Pandak WM.Localization of StarD5 cholesterol binding protein. Journal of Lipid Research. 2006. 47:1168-1175. (publishedMarch, 2006, doi:10.1194/jlr.M600019-JLR200Epub 2006 March).28.Li X, Hylemon PB, Pandak WM, and Ren S. Enzyme activity assay for sterol 27-hydroxylase (CYP27A1)in mitochondria. Journal of Lipid Research. 2006 Apr 3; [Epub ahead of print]PMID: 16585782 [PubMed - as supplied by publisher].29.Van Assche G, Sandborn WJ, Feagan BG, Salzberg B, Silvers D, Monroe P, Pandak WM, Anderson FH,Valentine JF, Wild GE, Geenen DJ, Sprague R, Targan SR, Rutgeerts PJ, Vexler V, Young D, Shames RS.Daclizumab, a humanized monoclonal antibody to the interleukin-2 receptor (CD25), for the treatment ofmoderately to severely active ulcerative colitis: a randomised, double-blind, placebo-controlled, dose-rangingtrial. Gut. 2006 Apr 7; [Epub ahead of print]30.Zhou H, Gurley EC, Jarujaron S, Ding H, Fang Y, Xu Z, Pandak WM, and Hylemon PB. HIV ProteaseInhibitors Activate the Unfolded Protein Response and Disrupt Lipid Metabolism in Primary Hepatocytes.American Journal of Physiology Gastrointestinal Liver Physiology. 2006 291: (In press).31.Shunlin R, Hylemon PB, Li X, Zhang Z-P, Rodriguez-Agudo D, Zhou H, Gil G, Erickson S, and PandakWM. Discovery of a Novel Oxysterol, 5-Cholesten-3beta, 25-Diol 3-Sulfonate, in Nuclei and MitochondriaFollowing Overexpression of the Gene Encoding StarD1. XIX International Bile Acid Meeting. In: Bile Acids:Biological Actions and Clinical Relevance. Falk Symposia #155, Beuers, Keppler, Leuschner, Stiehl, andTrauner (eds): Kluwer Academic Publishers, Kluwer Academic Publishers, 2006 (In press).32.Hylemon PB, Fang Y, Studer E, Pandak WM, and Dent P. Activation of a G-protein Coupled Receptor byConjugated Bile Acids in Primary Hepatocytes and Liver: Effects on Glucose Metabolism. XIX International BileAcid Meeting. In: Bile Acids: Biological Actions and Clinical Relevance. Falk Symposia #155, Beuers, Keppler,Leuschner, Stiehl, and Trauner (eds): Kluwer Academic Publishers, Kluwer Academic Publishers, 2006 (Inpress).PHS 398/2590 (Rev. 09/04) Page Continuation Format Page
  4. 4. Principal Investigator/Program Director (Last, First, Middle):C. RESEARCH SUPPORT (Ongoing Research Support)5 P01 DK38030-18 Hylemon (Program Director) 09/30/02-08/31/07NIH/NIDDKLiver/Intestinal Metabolism of Bile Acids/Cholesterol (Sub-project 2 - “Molecular Basis of CoordinateRegulation of Hepatic Cholesterol and Bile Acid Homeostasis”) The overall goal of this Program Project is aimed at a more detailed understanding of how the bodyregulates bile acid and cholesterol homeostasis, liver/intestinal physiology and determining if secondary bileacids are involved in the risk of cholesterol gallstone disease.Role: P.I. of Sub-project 2VA Merit Review Award Pandak (P.I.) 10/01/03 - 01/01/09Veterans AdministrationLipid Transporters, Bile Acid Synthesis, and Cholesterol Homeostasis The overall objective of this application is to study the relationship between the proteins involved inintracellular cholesterol transport and bile acid metabolism. We will utilize this relationship as a toolto study the role of 27-hydroxycholesterol, a regulatory oxysterol synthesized as a bile acid precursor of the"acidic pathway," in the regulation of cholesterol homeostasis.Role: P.I.1 R01 A1057189-01 Hylemon (P.I.) 03/01/04 – 02/28/09NIH/NIAIDHIV Protease Inhibitors and Hepatic Lipid Dysregulation The overalll objective of this application is to explore the mechanism(s) by which different HIV proteaseinhibitors alter hepatic cholesterol, bile acid and fatty acid metabolism.Role: Co-P.I.PHS 398/2590 (Rev. 09/04) Page Continuation Format Page