Faculty Summaries
Warren D Kruger, PhD
Warren D. Kruger, PhD
Professor
  • Professor, Fox Chase Cancer Center
  • Adjunct Professor, Temple University School of Medicine, Dept. of Pharmacology
  • Adjunct Professor, Department of Biochemistry and Molecular Biology, Drexel University College of Medicine
Warren.Kruger@fccc.edu
Office Phone: 215-728-3030
Fax: 215-214-1623
Office: P3029C

Original Articles

  • Tang B, Testa JR, Kruger WD. Increasing the therapeutic index of 5-flourouracil and 6-thioguanine by targeting loss of MTAP in tumor cells. Cancer Biol Ther. In Press (2012).
  • Gupta S. and Kruger, WD., Cystathionine Beta-synthase deficiency causes fat loss in mice. PLOS ONE 6: e27598 (2011).
  • Mustafa A., Gupta S., Hudes G.R., Egleston B.L., Uzzo RG, Kruger WD. Serum amino acid levels as a biomarker for renal cell carcinoma. J. Urology 186:1206-12 (2011).
  • Kadariya Y, Tang B, Myers CB, Fukui J, Peterson JR, Kruger WD. Chemical genetic screening for compounds that preferentially inhibit growth of methylthioadenosine phosphorylase (MTAP)-deficent Saccharomyces cerevisiae. J. Biomol. Screen 16:44-52 (2011)
  • Singh LR, Gupta S, Honig N, Kraus JP, Kruger WD. Activation of mutant enzyme function by proteasome inhibitors and treatments that induce Hsp70. PLOS Genetics Jan;6(1):e1000807, 2010.
  • Tang B, Mustafa A, Gupta S, Melnyk S, James SJ, Kruger WD. Methionine deficient diet induces post-transcriptional down-regulation of cystathionine beta-synthase. Nutrition 26:1170-1175, 2010).
  • Singh LR, Gupta S, Honig N, Kraus JP, Kruger WD. Activation of mutant enzyme function by proteasome inhibitors and treatments that induce Hsp70. PLOS Genetics Jan;6(1):e1000807, 2010.
  • Zhou JM, Portugal GS, Kruger WD, Wang H., Gould TJ, Pratico D. Diet-Induced hyperhomocysteinemia increases amyloid-beta formation and deposition in a mouse model of Alzheimer’s disease. Curr Alzheimer Res. 2010;7:140-9.
  • Zhou JM, Kruger WD, Pratico D. The Herp protein pathway is not involved in the pro-amyloidogenic effect of hyperhomocysteinemia. J Alzheimer’s Dis. 2010;20:569-76.
  • Wei Q, Wang L, Wang Q, Kruger WD, Dunbrack RL Jr. Testing computational prediction of missense mutation phenotypes: functional characterization of 204 mutations of human cystathionine beta synthase. Proteins. 2010;78:2058-74.
  • Strakova J, Williams KT, Gupta S, Schalinske KL, Kruger WD, Rozen R, Jiracek J, Li L, Garrow TA. Dietary intake of S-(alpha-carboxybutyl)-DL-homocysteine induces hyperhomocysteinemia in rats. Nutr Res. 2010;7:492-500.
  • Kozich V, Kruger WD. and Kraus JP. Cystathionine beta-Synthase (CBS) Deficiency: Genetics Encyclopedia of Life Sciences (2010).
  • Zhang DQ, Jiang XH, Fang P, Yan Y, Song J, Gupta S, Schafer AI, Durante W, Kruger WD, Yang XF, Wang H. Hyperhomocysteinemia promotes inflammatory monocyte generation and accelerates atherosclerosis in transgenic cystathionine beta-synthase deficient mice. Circulation. 2009;120:1893-902.
  • Jakubowski H, Perla-Kajan J, Finnell RH, Cabrera RM, Wang H, Gupta S, Kruger WD, Kraus JP, Shih DM. Genetic or nutritional disorders in homocysteine or folate metabolism increase protein N-homocysteinylation in mice. FASEB J. 2009 Jun;23(6):1721-7.
  • Singh LR, Kruger WD. Functional Rescue of Mutant Human Cystathionine beta-Synthase by Manipulation of Hsp26 and Hsp70 Levels in Saccharomyces cerevisiae. J Biol Chem. 2009 Feb;284(7):4238-45.
  • Zhang DQ, Jiang XH, Pu F, Yan Y, Song J, Wang LQ, Durante W, Yang XF, Kruger WD, Wang H. Hyperhomocysteinemia Modulates Monocyte Heterogeneity And Accelerates Atherosclerosis. Circulation. 2009 Oct;118(18):S467-S467.
  • Kadariya Y, Yin B, Tang BQ, Shinton SA, Quinlivan EP, Hua X, Klein-Szanto A, Al-Saleem TI, Bassing CH, Hardy RR, Kruger WD. Mice Heterozygous for Germ-line Mutations in Methylthioadenosine Phosphorylase (MTAP) Die Prematurely of T-Cell Lymphoma. Cancer Res. 2009 Jul;69(14):5961-9.
  • Gupta S, Kuhnisch J, Mustafa A, Lhotak S, Schlachterman A, Slifker MJ, Klein-Szanto A, High KA, Austin RC, Kruger WD. Mouse models of cystathionine beta-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia. FASEB J. 2009 Mar;23(3):883-93.
  • Zhang DQ, Jiang XH, Fang P, Yan Y, Song J, Gupta S, Schafer AI, Durante W, Kruger WD, Yang XF, Wang H. Hyperhomocysteinemia Promotes Inflammatory Monocyte Generation and Accelerates Atherosclerosis in Transgenic Cystathionine beta-Synthase-Deficient Mice. Arteriosclerosis Thrombosis and Vascular Biology. 2009 Jul;29(7):E109-E109.
  • Singh LR, Kruger WD. Functional rescue of mutant human cystathionine beta-synthase by manipulation of Hsp26 and Hsp70 levels in Saccharomyces cerevisiae. J Biol Chem. 2009 Feb 13;284(7):4238-45.
  • Gupta S, Wang L, Hua X, Krijt J, Kozich V, Kruger WD. Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice. Hum Mutat. 2008 Aug;29(8):1048-54.
  • Majtan T, Singh LR, Wang LQ, Kruger WD, Kraus JP. Active Cystathionine beta-Synthase Can Be Expressed in Heme-free Systems in the Presence of Metal-substituted Porphyrins or a Chemical Chaperone. J Biol Chem. 2008 Dec;283(50):34588-95.
  • Roy M, Leclerc D, Wu Q, Gupta S, Kruger WD, Rozen R. Valproic acid increases expression of methylenetetrahydrofolate reductase (MTHFR) and induces lower teratogenicity in MTHFR deficiency. J Cell Biochem. 2008 Oct;105(2):467-76.
  • Dayal S, Jensen MJ, Faraci FM, Kruger WD, Lentz SR. Endothelial Dysfunction and Paradoxical Resistance to Thrombosis in a Transgenic Mouse Model of Severe Hyperhomocysteinemia. 2008;:661.
  • Gupta S, Wang LQ, Hua X, Krijt J, Kozich V, Kruger WD. Cystathionine beta-synthase p.S466L mutation causes hyperhomocysteinemia in mice. Hum Mutat. 2008 Aug;29(8):1048-54.
  • Mustafa A, Kruger WD. Suppression of tumor formation by a cyclooxygenase-2 inhibitor and a peroxisome proliferator-activated receptor gamma agonist in an in vivo mouse model of spontaneous breast cancer. Clin Cancer Res. 2008 Aug 1;14(15):4935-42.
  • van Slegtenhorst M, Khabibullin D, Hartman TR, Nicolas E, Kruger WD, Henske EP. The Birt-Hogg-Dube and tuberous sclerosis complex homologs have opposing roles in amino acid homeostasis in Schizosaccharomyces pombe. J Biol Chem. 2007 Aug 24;282(34):24583-90.
  • Singh LR, Chen X, Koz ich V, Kruger WD. Chemical chaperone rescue of mutant human cystathionine beta-synthase. Mol Genet Metab. 2007 Aug;91(4):335-42.
  • Park ES, Oh HJ, Kruger WD, Jung SC, Lee JS. Recombinant adeno-associated virus mediated gene transfer in a mouse model for homocystinuria. Exp Mol Med. 2006 Dec;38(6):652-61.
  • Pei JM, Kruger WD, Testa JR. High-resolution analysis of 9p loss in human cancer cells using single nucleotide polymorphism-based mapping arrays. Cancer Genet Cytogenet. 2006 Oct;170(1):65-8.
  • Chen X, Wang L, Fazlieva R, Kruger WD. Contrasting behaviors of mutant cystathionine beta-synthase enzymes associated with pyridoxine response. Hum Mutat. 2006 Apr 17;27(5):474-82.
  • Tang BQ, Kadariya Y, Murphy ME, Kruger WD. The methionine salvage pathway compound 4-methylthio-2oxobutanate causes apoptosis independent of down-regulation of ornithine decarboxylase. Biochem Pharmacol. 2006 Sep;72(7):806-15.
  • Kadariya Y, Nakatani K, Nishioka J, Fujikawa T, Kruger WD, Nobori T. Regulation of human methylthioadenosine phosphorylase gene by the CBF (CCAAT binding factor)/NF-Y (nuclear factor-Y). Biochem J. 2005 Part 1 APR 1;387:175-83.
  • Wang LQ, Chen XL, Tang BQ, Hua X, Klein-Szanto A, Kruger WD. Expression of mutant human cystathionine beta-synthase rescues neonatal lethality but not homocystinuria in a mouse model. Hum Mol Genet. 2005 Aug 1;14(15):2201-8.
  • Jhee KH, Kruger WD. The role of cystathionine beta-synthase in homocysteine metabolism. Antioxidants & Redox Signaling. 2005 May-Jun;7(5-6):813-22.
  • Oh HJ, Park ES, Kruger W, Jung SC, Lee JS. Human CBS (cystathionine beta-synthase) gene transfer mediated by recombinant adeno-associated virus vector. Molecular Therapy. 2004 May;9:S69-S70.
  • Subhi AL, Tang B, Balsara BR, Altomare DA, Testa JR, Cooper HS, Hoffman JP, Meropol NJ, Kruger WD. Loss of methylthioadenosine phosphorylase and elevated ornithine decarboxylase is common in pancreatic cancer. Clin Cancer Res. 2004 Nov 1;10(21):7290-6.
  • Singh RH, Kruger WD, Wang LQ, Pasquali M, Elsas LJ. Cystathionine beta-synthase deficiency: Effects of betaine supplementation after methionine restriction in B6-nonresponsive homocystinuria. Genetics in Medicine. 2004 Mar-Apr;6(2):90-5.
  • Chen XL, Jhee KH, Kruger WD. Production of the neuromodulator H2S by cystathionine beta-synthase via the condensation of cysteine and homocysteine. J Biol Chem. 2004 Dec 10;279(50):52082-6.
  • Tang BQ, Kruger WD, Chen G, Shen FM, Lin WY, Mboup S, London WT, Evans AA. Hepatitis B viremia is associated with increased risk of hepatocellular carcinoma in chronic carriers. J Med Virol. 2004 Jan;72(1):35-40.
  • van Slegtenhorst M, Carr E, Stoyanova R, Kruger WD, Henske EP. Tsc1(+) and tsc2(+) regulate arginine uptake and metabolism in Schizosaccharomyces pombe. J Biol Chem. 2004 Mar;279(13):12706-13.
  • Wang LQ, Jhee KH, Hua X, DiBello PM, Jacobsen DW, Kruger WD. Modulation of cystathionine beta-synthase level regulates total serum homocysteine in mice. Circ Res. 2004 May;94(10):1318-24.
  • Subhi AL, Diegelman P, Porter CW, Tang BQ, Lu ZC, Markham GD, Kruger WD. Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolites. J Biol Chem. 2003 Dec;278(50):49868-73.
  • Kruger WD, Wang L, Jhee KH, Singh RH, Elsas LJ. Cystathionine beta-synthase deficiency in Georgia (USA): Correlation of clinical and biochemical phenotype with genotype. Hum Mutat. 2003 Dec;22(6):434-41.
  • Cheon MS, Bajo M, Kim SH, Claudio JO, Stewart AK, Patterson D, Kruger WD, Kondoh H, Lubec G. Protein levels of genes encoded on chromosome 21 in fetal Down syndrome brain: Challenging the gene dosage effect hypothesis (Part II). Amino Acids. 2003 Mar;24(1-2):119-25.
  • Christopher SA, Diegelman P, Porter CW, Kruger WD. Methylthioadenosine Phosphorylase, a Gene Frequently Codeleted with p16(cdkN2a/ARF), Acts as a Tumor Suppressor in a Breast Cancer Cell Line. Cancer Res. 2002 Nov 15;62(22):6639-44.
  • Christopher SA, Melnyk S, James SJ, Kruger WD. S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase. Mol Genet Metab. 2002 Apr;75(4):335-43.
  • Shan X, Dunbrack RL, Christopher SA, Kruger WD. Mutations in the regulatory domain of cystathionine beta synthase can functionally suppress patient-derived mutations in cis. Hum Mol Genet. 2001 Mar 15;10(6):635-43.
  • Nozaki T, Shigeta Y, Saito-Nakano Y, Imada M, Kruger WD. Characterization of transsulfuration and cysteine biosynthetic pathways in the protozoan hemoflagellate, Trypanosoma cruzi. Isolation and molecular characterization of cystathionine beta-synthase and serine acetyltransferase from Trypanosoma. J Biol Chem. 2001 Mar 2;276(9):6516-23.
  • Malinow MR, Duell PB, Williams MA, Kruger WD, Evans AA, Anderson PH, Block PC, Hess DL, Upson BM, Graf EE, Irvin-Jones A, Wang LQ. Short-term folic acid supplementation induces variable and paradoxical changes in plasma homocyst(e)ine concentrations. Lipids. 2001 Suppl. S;36:S27-S32.
  • Strizheva GD, Carsillo T, Kruger WD, Sullivan EJ, Ryu JH, Henske EP. The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med. 2001 Jan;163(1):253-8.
  • Guttormsen AB, Ueland PM, Kruger WD, Kim CE, Ose L, Folling I, Refsum H. Disposition of homocysteine in subjects heterozygous for homocystinuria due to cystathionine beta-synthase deficiency: relationship between genotype and phenotype. Am J Med Genet. 2001 May 1;100(3):204-13.
  • Kruger WD. The transsulfuration pathway. In: Carmel R, Jacobsen DW, editors. Homocysteine in health and disease. Cambridge, UK ; New York: Cambridge University Press; 2001. p. 153-61.
  • Steen MT, Kruger WD, Wong L, Dunbrack R, Elsas LJ. Identification of a novel mutation in cystathionine beta- synthase (CBS) among American Blacks. Am J Hum Genet. 2000 Oct;67(4):1637.
  • Malinow MR, Duell PB, Williams MA, Kruger WD, Anderson P, Gluckman RA, Block PC, Upson BM, Graf EE, Irvin-Jones A. Paradoxical response of plasma homocyst(e)ine to folic acid supplementation. FASEB J. 2000 Mar 15;14(4):A726-A726.
  • Astrinidis A, Strizheva GD, Carsillo T, Kruger W, Sullivan EJ, Ryu JH, Henske EP. Evidence of a correlation between germline mutations in the carboxy-terminus of tuberin (TSC2) and pulmonary lymphangiomyomatosis. Am J Hum Genet. 2000 Oct;67(4):2240.
  • Kruger WD. Vitamins and homocysteine metabolism. Vitam Horm. 2000;60:333-52.
  • Kruger WD, Evans AA, Wang L, Malinow MR, Duell PB, Anderson PH, Block PC, Hess DL, Graf EE, Upson B. Polymorphisms in the CBS gene associated with decreased risk of coronary artery disease and increased responsiveness to total homocysteine lowering by folic acid. Mol Genet Metab. 2000 May;70(1):53-60.
  • Kruger WD, Fowler B. Molecular biology of cystathionine b-synthase: interrelationships with homocysteine, pyridoxine, and vascular disease. In: Robinson K, editor. Homocysteine and Vascular Disease. Dordrecht, The Netherlands: Kluwer Press; 2000. p. 313-33.
  • Kruger WD, Shan X. Missense mutations in the regulatory domain of cystathionine beta-synthase can functionally suppress patient derived mutations in cis. Am J Hum Genet. 2000 Oct;67(4):1512.
  • Kruger WD, Tew KD. Pharmacogenetics and cancer. In: Kruh GD, Tew KD, editors. Basic Science of Cancer. Philadelphia, PA: Current Med. Inc.; 2000. p. 257-70.
  • Tang B, Li YN, Kruger WD. Defects in methylthioadenosine phosphorylase are associated with but not responsible for methionine-dependent tumor cell growth. Am J Hum Genet. 2000 Oct;67(4):310.
  • Shan X, Wang L, Hoffmaster R, Kruger WD. Functional characterization of human methylenetetrahydrofolate reductase in Saccharomyces cerevisiae. J Biol Chem. 1999 Nov 12;274(46):32613-8.
  • Lobo A, Naso A, Arheart K, Kruger WD, Abou-Ghazala T, Alsous F, Nahlawi M, Gupta A, Moustapha A, van Lente F, Jacobsen DW, Robinson K. Reduction of homocysteine levels in coronary artery disease by low-dose folic acid combined with vitamins B-6 and B-12. Am J Cardiol. 1999 Mar 15;83(6):821-5.
  • Kruger WD, Wang L, Evans AA, Malinow MR, Duell PB, Hess DL, Gluckman RA, Block PC, Anderson PH, Upson B. Polymorphisms in the CBS gene associated with increased risk of heart disease and decreased responsiveness to homocysteine lowering by folate. Am J Hum Genet. 1999 Oct;65(4):2403.
  • Chen P, Poddar R, Tipa EV, Dibello PM, Moravec CD, Robinson K, Green R, Kruger WD, Garrow TA, Jacobsen DW. Homocysteine metabolism in cardiovascular cells and tissues: Implications for hyperhomocysteinemia and cardiovascular disease. In: Advances in Enzyme Regulation, Vol 39. 1999. p. 93-109.
  • Shan X, Kruger WD. Correction of disease-causing CBS mutations in yeast. Nat Genet. 1998 May;19(1):91-3.
  • Malinow MR, Duell PB, Hess DL, Anderson PH, Kruger WD, Phillipson BE, Gluckman RA, Block PC, Upson BM. Reduction of plasma homocyst(e)ine levels by breakfast cereal fortified with folic acid in patients with coronary heart disease. N Engl J Med. 1998 Apr 9;338(15):1009-15.
  • Boddie AM, Steen MT, Langley SD, Cotsonis GA, Elasa LJ, Kruger WD. Folate indices are lower in genotyped carriers for cystathionine-beta-synthase (C beta S) deficiency than in non- carrier family members. FASEB J. 1998 Mar 17;12(4):2971.
  • Taoka S, Ohja S, Shan XY, Kruger WD, Banerjee R. Evidence for heme-mediated redox regulation of human cystathionine beta-synthase activity. J Biol Chem. 1998 Sep 25;273(39):25179-84.
  • Kim CE, Gallagher PM, Guttormsen AB, Refsum H, Ueland PM, Ose L, Folling I, Whitehead AS, Tsai MY, Kruger WD. Functional modeling of vitamin responsiveness in yeast: a common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria. Hum Mol Genet. 1997 Dec;6(13):2213-21.
  • Shan X, Kruger WD. Intragenic suppression of human cystathionine beta-synthase mutations. Am J Hum Genet. 1997 Oct;61(4):2420.
  • Malinow MR, Nieto FJ, Kruger WD, Duell PB, Hess DL, Gluckman RA, Block PC, Holzgang CR, Anderson PH, Seltzer D, Upson B, Lin QR. The effects of folic acid supplementation on plasma total homocysteine are modulated by multivitamin use and methylenetetrahydrofolate reductase genotypes. Arteriosclerosis Thrombosis and Vascular Biology. 1997 Jun;17(6):1157-62.
  • Wang L, Upson B, Malinow MR, Duell PB, Hess DL, Gluckman RA, Block PC, Holzgang CR, Anderson PH, Seltzer D, Kruger W. Genetic alterations in homocysteine metabolizing genes and coronary heart disease. Am J Hum Genet. 1997 Oct;61(4):2271.
  • Kruger WD, Gallagher PM, Guttormsen AB, Refsum H, Ueland PM, Whitehead AS, Tsai MY, Kim CE. Functional modeling of vitamin responsiveness in yeast: A common pyridoxine-responsive cystathionine beta-synthase mutation in homocystinuria. Am J Hum Genet. 1997 Oct;61(4):282.
  • Li YN, Gulati S, Baker PJ, Brody LC, Banerjee R, Kruger WD. Cloning, mapping and RNA analysis of the human methionine synthase gene. Hum Mol Genet. 1996 Dec;5(12):1851-8.
  • Gulati S, Baker P, Li YN, Fowler B, Kruger W, Brody LC, Banerjee R. Defects in human methionine synthase in cblG patients. Hum Mol Genet. 1996 Dec;5(12):1859-65.