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
Genetic defects in methionine and amino acid metabolism and cancer

Amino acids are the building blocks of proteins and other important biological molecules. The sulfur containing amino acid methionine is especially interesting as alterations in methionine metabolism and methionine-related pathways are found in many human diseases (Figure 1), including rare inborn errors of metabolism to common diseases such as cardiovascular disease and cancer. Currently there are three major projects in the lab. Two concern particular methionine metabolic genes, cystathionine beta-synthase (CBS) and methylthioadenosine phosphorylase (MTAP). A third project is related to understanding how alterations in amino acid metabolism contributes to renal cell carcinoma.

Description of research projects
Selected Publications
  1. Gupta S, Wang L, Kruger WD. Betaine supplementation is less effective than methionine restriction in correcting phenotypes of CBS deficient mice. J Inherit Metab Dis. 2015 Aug 1. [Epub ahead of print] (2015) PMID: 26231230
  2. Lee HO, Mustafa A, Hudes GR, Kruger WD. Hydroxychloroquine Destabilizes Phospho-S6 in Human Renal Carcinoma Cells. PLoS One. 2015 10:e0131464. doi: 10.1371/journal.pone.0131464 (2015). PMID: 26134285
  3. Tang B.Kadariya Y, Chen Y, Slifker M, Kruger WD Expression of MTAP inhibits tumor-related phenotypes in HT1080 cells via a mechanism unrelated to its enzymatic function.G3 5:35-44. doi: 10.1534/g3.114.014555. (2015). PMID: 25387827
  4. Shlomi T, Fan J, Tang B, Kruger WD, Rabinowitz JD. Quantitation of cellular metabolic fluxes of methionine. Anal Chem. 86:1583-91.  (2014) PMID: 24397525
  5. Gupta S, Melnyk SB, Kruger WD. Cystathionine β-synthase-deficient mice thrive on a low methionine diet. FASEB J. 28:781-90 (2014). PMID: 24189943
  6. Kadariya Y, Tang B, Al-Saleem T, Hayakawa K, Slifker M, Kruger WD Germline Mutations in Mtap Cooperate with Myc and Pten to Accelerate tumorigenesis in Mice
    PloS One 8: e67635. (2013) PMID: 23840755
  7. Gupta S, Wang L, Anderl J, Slifker M, Kirk C, Kruger WD Correction of an inborn error of metabolism using proteasome inhibitors.  Hum. Mutat. 34: 1085-93 (2013) PMID: 23592311
  8. 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.  13:1082-1090 (2012). PMID: 22825330
  9. Gupta S. and Kruger, WD., Cystathionine Beta-synthase deficiency causes fat loss in mice.  PLOS ONE 6: e27598 (2011). PMID: 22096601
  10. 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). PMID: 21849193 (Selected by Faculty of 1000)
  11. 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) PMID: 21131597.
  12. 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. PMID: 20066033 (Selected by Faculty of 1000)
  13. Kadariya Y, Yin B, Tang B, Shinton SA, Quinlivan EP, Hua X, Klein-Szanto A, Al-Saleem TI, Bassing CH, Hardy RR, Kruger WD.  Mice Heterozygous for germline mutations in methylthioadenosine phosphorylase (MTAP) die prematurely of T-cell lymphoma.  Cancer Res. 69: 5961-5969, 2009. PMID: 19567676
  14. Singh LR, Kruger WD.  Functional rescue of mutant human cystathionine b-synthase by manipulation of Hsp26 and Hsp70 levels in Saccharomyces cerevisiae. J. Biol. Chem.284:4238-4245, 2009. PMID: 19074437
  15. Gupta S, Kühnisch J, Mustafa A, Lhotak S, Schlachterman A, Slifker MJ, Klein-Szanto A, High KA, Austin RC, Kruger WD.  Mouse models of cystathionine b-synthase deficiency reveal significant threshold effects of hyperhomocysteinemia. FASEB J. 23:883-893, 2009. PMID: 18987302
All publications