Recent publications of lab members

  1. Sharma, V.K.*, Stark, M.*, Fridman, N., Assaraf, Y.G. and Gross, G. (2022) Doubly Stimulated Corrole for Organelle-Selective Antitumor Cytotoxicity. J Med Chem. 65(8):6100-6115. * Both authors equally contributed. PubMed
  2. Stark, M., Raz, S. and Assaraf, Y.G. (2021) Folylpoly-ɣ-glutamate synthetase association to the cytoskeleton: Implications to folate metabolon compartmentalization. Journal of Proteomics. PubMed
  3. Levin, M., Stark, M., Ofran, Y. and Assaraf, Y.G. (2021) Deciphering molecular mechanisms underlying chemoresistance in relapsed AML patients: towards precision medicine overcoming drug resistance. Cancer Cell Int. 21(1):53.  PubMed
  4. Stark, M., Silva, T.F.D., Levin, G., Machuqueiro, M. and Assaraf, Y.G. (2020) The lysosomotropic activity of hydrophobic weak base drugs is mediated via their intercalation into the lysosomal membrane. Cells. 9(5), 1082. PubMed
  5. Lehvy, A.I., Horev, G., Golan, Y., Glaser, F., Shammai, Y. and Assaraf, Y.G. (2019) Alterations in ZnT1 expression and function lead to impaired intracellular zinc homeostasis in cancer. Cell Death Discov. 5:144. PubMed
  6. Golan, Y., Alhadeff, R., Warshel, A. and Assaraf, Y.G. (2019) ZnT2 is an electroneutral proton-coupled vesicular antiporter displaying an apparent stoichiometry of two protons per zinc ion. PLoS Comput Biol.   15(3):e1006882.  PubMed
  7. Levin, M., Stark, M., Berman, B. and Assaraf, Y.G. (2019) Surmounting Cytarabine-resistance in acute myeloblastic leukemia cells and specimens with a synergistic combination of hydroxyurea and azidothymidine. Cell Death & Disease. 10(6):390.  PubMed
  8. Golan, Y., Lehvy, A., Horev, G. and Assaraf, Y.G. (2018) High proportion of transient neonatal zinc deficiency causing alleles in the general population. J Cell Mol Med. 23(2):828-840. PubMed
  9. Zhitomirsky, B., Yunaev, A., Kreiserman, R., Stark, M. Kaplan, A.and Assaraf, Y.G. (2018) Lysosomotropic drugs activate TFEB via lysosomal membrane fluidization and consequent inhibition of mTORC1 activity. Cell Death Dis. 9(12):1191. PubMed  CDD
  10. Golan, Y., Alhadeff, R., Glaser, F., Ganoth, A., Warshel, A. and Assaraf, Y.G. (2018) Demonstrating aspects of multiscale modeling by studying the permeation pathway of the human ZnT2 zinc transporter. PLoS Comput Biol. 14(11):e1006503. PubMed 
  11. Levin, M., Stark, M. and Assaraf, Y.G. (2018) The JmjN domain as a dimerization interface and a targeted inhibitor of KDM4 demethylase activity. Oncotarget. 9 (24): 16861-16882. Oncotarget    PubMed 
  12. Engelberg, S., Modrejewski, J., Walter, J.G., Livney, Y.D. and Assaraf, Y.G. (2018) Cancer cell-selective, clathrin-mediated endocytosis of aptamer-decorated nanoparticles. Oncotarget. 9(30):20993-21006.
  13. Zhitomirsky, B., Farber, H. and Assaraf, Y.G. (2018) LysoTracker and MitoTracker Red are transport substrates of P-glycoprotein: implications for anticancer drug design evading multidrug resistance. J Cell Mol Med. 22(4):2131-2141. PubMed
  14. Golan, Y.,Yerushalmi, B., Efrati, E. and Assaraf, Y.G. (2017) Identification of Genetic Diseases Using Breast Milk Cell Analysis: The Case of Transient Neonatal Zinc Deficiency (TNZD). Cell Mol Med. 3(2): 8. CMM
  15. Stark, M. and Assaraf, Y.G. (2017) Structural recognition of tubulysin B derivatives by multidrug resistance efflux transporters in human cancer cells. Oncotarget. 8(30):49973-49987. PubMed
  16. Zhitomirsky, B. and Assaraf, Y.G. (2017) Lysosomal accumulation of anticancer drugs triggers lysosomal exocytosis. Oncotarget. 8(28):45117-45132 PubMed
  17. Golan, Y., Itsumura, N., Glaser, F., Berman, B., Kambe, T. and Assaraf, Y.G. (2016) Molecular Basis of Transient Neonatal Zinc Deficiency: Novel ZnT2 Mutations Disrupting Zinc Binding and Permeation. J Biol Chem291(26):13546-59. PubMed
  18. Zhitomirsky, B. and Assaraf, Y.G. (2015) The role of cytoplasmic-to-lysosomal pH gradient in hydrophobic weak base drug sequestration in lysosomes. Cancer Cell & Microenvironment. Vol 2, No 2 doi: 10.14800/ccm.807. CCM
  19. Golan, Y., Berman, B. and Assaraf, Y.G. (2015) Heterodimerization, altered subcellular localization and function of multiple zinc transporters in viable cells using bimolecular fluorescence complementation. J Biol Chem. 290(14):9050-63  PubMed
  20. Zhitomirsky, B. and Assaraf, Y.G. (2015) Lysosomal sequestration of hydrophobic weak base chemotherapeutics triggers lysosomal biogenesis and lysosome-dependent cancer multidrug resistance. Oncotarget. 6(2):1143-56. PubMed
  21. Raz, S.,  Stark, M. and Assaraf, Y.G. (2014) The intricate role of Smads in the regulation of FPGS gene expression. Cancer Cell & Microenvironment. Vol 1, No 6 doi: 10.14800/ccm.425 CCM
  22. Raz, S.,  Stark, M. and Assaraf, Y.G. (2014) Binding of a Smad4/Ets-1 complex to a novel intragenic regulatory element in exon12 of FPGS underlies decreased gene expression and antifolate resistance in leukemia. Oncotarget.  5(19):9183-9198. PubMed
  23. Raz, S., Sheban, D., Gonen, N., Stark, M., Berman, B. and Assaraf, Y.G. (2014) Severe hypoxia induces complete antifolate resistance in carcinoma cells due to cell cycle arrest. Cell Death Dis. 5:e1067. PubMed
  24. Lasry, I., Golan, Y., Berman, B., Amram, N., Glaser, F. and Assaraf, Y.G. (2014) In situ dimerization of multiple wild type and mutant zinc transporters in live cells using bimolecular fluorescence complementation. J Biol Chem. 289(11):7275-92. PubMed
  25. Lasry, I., Seo, Y.A., Ityel, H., Shalva, N., Pode-Shakked, B., Glaser, F., Berman, B., Berezovsky, I., Goncearenco, A., Klar, A., Levy, J., Anikster, Y., Kelleher, S.L. and Assaraf, Y.G. (2012) A dominant negative heterozygous G87R mutation in the zinc transporter, ZnT-2 (SLC30A2), results in transient neonatal zinc deficiency. J Biol Chem. 287(35):29348-61. PubMed
  26. Goler-Baron, V. and Assaraf, Y.G. (2012) Overcoming multidrug resistance via photodestruction of ABCG2-rich extracellular vesicles sequestering photosensitive chemotherapeutics. Plos One. 7(4):e35487. PubMed
  27. Adar, Y., Stark, M., Bram, E.E., Nowak-Sliwinska, P., van den Bergh, H., Szewczyk, G., Sarna, T., Skladanowski, A., Griffioen, A.W. and Assaraf, Y.G. (2012) Imidazoacridinone-dependent lysosomal photodestruction: a pharmacological Trojan horse approach to eradicate multidrug-resistant cancers. Cell Death Dis. 3:e293. PubMed
  28. Goler-Baron, V., Sladkevich, I. and Assaraf, Y.G. (2012) Inhibition of the PI3K-Akt signaling pathway disrupts ABCG2-rich extracellular vesicles and overcomes multidrug resistance in breast cancer cells. Biochem Pharmacol. 83(10):1340-8. PubMed
  29. Goler-Baron, V. and Assaraf, Y.G. (2011) Structure and function of ABCG2-rich extracellular vesicles mediating multidrug resistance. Plos One. 6(1):e16007. PubMed
  30. Stark, M., Bram, E.E., Akerman, M., Mandel-Gutfreund, Y. and Assaraf, Y.G. (2011) Heterogeneous nuclear ribonucleoprotein H1/H2-dependent unsplicing of thymidine phosphorylase results in anticancer drug resistance. J Biol Chem. 286(5):3741-54. PubMed
  31. Gonen, N. and Assaraf, Y.G. (2010) The obligatory intestinal folate transporter PCFT (SLC46A1) is regulated by nuclear respiratory factor 1. J Biol Chem. 285(44):33602-13. PubMed
  32. Bram, E.E., Stark, M., Raz, S. and Assaraf, Y.G. (2009) Chemotherapeutic drug-induced ABCG2 promoter demethylation as a novel mechanism of acquired multidrug resistance. Neoplasia. 11(12):1359-70. PubMed
  33. Stark, M.*, Gonen, N.* and Assaraf, Y.G. (2009) Functional elements in the minimal promoter of the human proton-coupled folate transporter. Biochem Biophys Res Commun. 388(1):79-85. * Both authors equally contributed. PubMed
  34. Lasry, I., Berman, B., Glaser, F., Jansen, G. and Assaraf, Y.G. (2009) Hereditary folate malabsorption: a positively charged amino acid at position 113 of the proton-coupled folate transporter (PCFT/SLC46A1) is required for folic acid binding. Biochem Biophys Res Commun. 386(3):426-31. PubMed
  35. Bram, E.E., Adar, Y., Mesika, N., Sabisz, M., Skladanowski, A. and Assaraf, Y.G. (2009) Structural determinants of imidazoacridinones facilitating antitumor activity are crucial for substrate recognition by ABCG2. Mol Pharmacol. 75(5):1149-59. PubMed
  36. Ifergan, I., Goler-Baron, V. and Assaraf, Y.G. (2009) Riboflavin concentration within ABCG2-rich extracellular vesicles is a novel marker for multidrug resistance in malignant cells. Biochem Biophys Res Commun. 380: 5-10. PubMed
  37. Stark, M., Wichman, C., Avivi, I. and Assaraf, Y.G. (2009) Aberrant splicing of folylpolyglutamate synthetase as a novel mechanism of antifolate resistance in leukemia. Blood. 113(18):4362-9. PubMed
  38. Gonen, N., Bram, E.E. and Assaraf, Y.G. (2008) PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells. Biochem Biophys Res Commun. 376: 787-792. PubMed
  39. Lasry, I., Berman, B., Straussberg, R., Sofer, Y., Bessler, H., Sharkia, M., Glaser, F., Jansen, G., Drori, S. and Assaraf, Y.G. (2008) A novel loss-of-function mutation in the proton-coupled folate transporter from a patient with hereditary folate malabsorption reveals that Arg 113 is crucial for function. Blood. 112: 2055-2061. PubMed
  40. Ifergan, I., Jansen, G. and Assaraf, Y.G. (2008) The reduced folate carrier (RFC) is cytotoxic to cells under conditions of severe folate deprivation: RFC as a double-edged sword in folate homeostasis. J Biol Chem. 283(30):20687-95.
  41. Bram, E., Ifergan, I., Grimberg, M., Lemke, K., Skladanowski, A., and Assaraf, Y.G. (2007) C421 allele-specific ABCG2 gene amplification confers resistance to the antitumor triazoloacridone C-1305 in human lung cancer cells. Biochem Pharmacol. 74: 41-53.
  42. Bram, E., Ifergan, I., Shafran, A., Berman, B., Jansen, G., and Assaraf, Y.G. (2006) Mutant Gly482 and Thr482 ABCG2 mediate high-level resistance to lipophilic antifolates. Cancer Chemother Pharmacol. 58: 826-834.
  43. Kaufman, Y., Ifergan, I., Rothem, L., Jansen, G., and Assaraf, Y.G. (2006) Coexistence of multiple mechanisms of PT523 resistance in human leukemia cells harboring 3 reduced folate carrier alleles: transcriptional silencing, inactivating mutations, and allele loss. Blood. 107: 3288-3294.
  44. Stark, M., and Assaraf, Y.G. (2006) Loss of Sp1 function via inhibitory phosphorylation in antifolate-resistant human leukemia cells with down-regulation of the reduced folate carrier. Blood. 107: 708-715.
  45. Ifergan, I., Scheffer, G.L., and Assaraf, Y.G. (2005) Novel extracellular vesicles mediate an ABCG2-dependent anticancer drug sequestration and resistance. Cancer Res. 65: 10952-10958.
  46. Shafran, A., Ifergan, I., Bram, E., Jansen, G., Kathmann, I., Peters, G.J., Robey, R.W., Bates, S.E., and Assaraf, Y.G. (2005) ABCG2 harboring the Gly482 mutation confers high level resistance to various antifolates.  Cancer Res. 65: 8414-8422.
  47. Rothem, L., Berman, B., Stark, M., Jansen, G., and Assaraf, Y.G. (2005) The reduced folate carrier gene is a novel selectable marker for recombinant protein overexpression. Mol Pharmacol. 68: 616-624.
  48. Ifergan, I., Jansen, G., and Assaraf, Y.G. (2005) Cytoplasmic confinement of breast cancer resistance protein (BCRP/ABCG2) as a novel mechanism of adapation to short-term folate deprivation. Mol. Pharmacol. 67: 1349-1359.
  49. Rothem, L.*, Stark, M.*, and Assaraf, Y.G. (2004) Impaired CREB-1 phosphorylation in antifolate-resistant cell lines with down regulation of the reduced folate carrier gene. Mol. Pharmacol. 66: 1536-1543. * Both authors equally contributed.
  50. Ifergan, I., Shafran, A., Jansen, G., Hooijberg, J.H., Scheffer, G.L., and Assaraf, Y.G. (2004) Folate deprivation results in the loss of breast cancer resistance protein (ABCG2) expression: a role for BCRP in cellular folate homeostasis.  J. Biol. Chem. 279: 25527-25534.
  51. Kaufman, Y., Drori, S., Cole, P.D., Kamen, B.A., Sirota, J., Ifergan, I., Rechavi, G., Toren, A., Weyl Ben-Arush, M., Elhasid, R., Sahar, D., Kaspers, G.J.L., Matherly, L.H., Jansen, G.,  and Assaraf, Y.G. (2004) Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia. Cancer 100: 773-782.
  52. Rothem, L.*, Stark, M.*, Kaufman, Y., Mayo, L., and Assaraf, Y.G. (2004) Reduced folate carrier gene silencing in multiple antifolate-resistant tumor cell lines is due to a simultaneous loss of function of multiple transcription factors but not promoter methylation. J. Biol. Chem. 279: 374-384. * Both authors equally contributed.
  53. Ifergan, I., Meller, I., Issakov, J., and  Assaraf, Y.G.  (2003) Reduced folate carrier protein expression in osteosarcoma: implications for the prediction of tumor chemosensitivity. Cancer 98: 1958-1966.
  54. Stark, M., Rothem, L., Scheffer, G.L., Jansen, G., Goldman, I.D., and Assaraf, Y.G. (2003) Antifolate resistance associated with loss of MRP1 expression and function in Chinese hamster ovary cells with markedly impaired export of folate and cholate. Mol. Pharmacol. 64: 220-227.
  55. Rothem, L., Aronheim, A., and Assaraf, Y.G. (2003) Alterations in the expression of transcription factors and the reduced folate carrier as a novel mechanism of antifolate resistance in human leukemia cells. J. Biol. Chem. 278: 8935-8941.
  56. Liani, E., Rothem, L., Bunni, M.A., Smith, C.A., Jansen, G., and Assaraf, Y.G. (2003) Loss of folylpoly-γ-glutamate synthetase activity is a dominant mechanism of resistance to polyglutamylation-dependent novel antifolates in multiple human leukemia sublines. Int. J. Cancer 103: 587-599.