Dan Zilberstein

Dan Zilberstein

Education/ Resume:

1983   Ph.D. in Microbiology and Biochemistry, Hebrew University of Jerusalem Israel.

1977   M.Sc. in Environmental Sciences with distinction, Hebrew University of Jerusalem.

1975   B.Sc. in Biology, Hebrew University of Jerusalem, Israel.

Research interest
  • Assessment of the molecular mechanism of Leishmania development inside its host
  • The arginine sensing pathway in Leishmania and assessment of its role in virulence and host-pathogen interaction
Key Publications

Leishmania intracellular development

Barak, E., Amin-Spector, S., Gerliak, E., Goyard, S., Holland, N. and Zilberstein, D. Differentiation of Leishmania donovani in host-free system: analysis of signal perception and response. Mol. Biochem. Parasitol. 141, 99-108, (2005). PubMed PMID: 15811531.

Rosenzweig, D., Smith, D., Opperdoes, F.R., Stern, S., Olafson, R.W. and Zilberstein, D. Retooling Leishmania metabolism: from sandfly gut to human macrophage. The FASEB Journal 22, 590-602, (2008). PubMed PMID: 17884972.

Lahav, T., Sivam, D, Volpin, H., Holland, N., Anderson-Green, A., Zilberstein, D. and Myler, P.J.§ Multiple levels of gene regulation mediate differentiation of the intracellular pathogen Leishmania donovani. FASEB J. 25, 515-525, (2011). PubMed PMID: 20952481.

Tsigankov, P., Gherardini, F.P., Helmer-Citterich, M., Späth, G.F., Myler, P.J., Zilberstein, D. Regulation dynamics of Leishmania differentiation: deconvoluting signals and identifying phosphorylation trends. Mol. & Cell. Prot., 13, 1769-1786 (2014). PubMed PMID: 24741111.

Bachmaier, S., Witztum, R., Tsigankov, P., Koren, R., Boshart, M., Zilberstein, D. Protein kinase A signaling during bidirectional axenic differentiation of Leishmania, Int J Parasitol, 46, 75-82 (2016). PubMed PMID: 26460237.

Liburkin-Dan, T., Schlisselberg, D., Fischer-Weinberger, R., Pescher, P., Inbar, E., Rentsch, D., Späth, G.F., Myler, P.J. and Zilberstein, D. Stage-specific expression of the proline-alanine transporter in the human pathogen Leishmania. Mol. Biochem. Parasitol. 222, 1-5 (2018). PubMed PMID: 29655799.

Zilberstein, D. and Nitzan Koren, R. Host-Free Systems for Differentiation of Axenic Leishmania. Meth. Mol. Biol 1971: 1-8 (2019). PubMed PMID: 30980296.

Zilberstein, D. Lysosome Sensing Is a Key Mechanism in Leishmania Intracellular Development. Front Microbiol 12, 667807 (2021). PubMed PMID: 34025623.

Fischer-Weinberger, R., Bachmaier, S., Ober, V., Githur, G.B., Dandugudumula, R., Phan, I.A., Almoznino, M., Polatoglou, E., Tsigankov, P., Nitzan Koren, R., Myler, P.J., Boshart, M. and Zilberstein, D. A divergent protein kinase A regulatory subunit essential for morphogenesis of the human pathogen Leishmania. PLoS Pathogens, 20: e1012073 (2024). PubMed PMID: 38551993.

 

The arginine sensing pathway in Leishmania

Darlyuk, I., Goldman A., Roberts, S.C., Ullman, B., Rentschm D. and Zilberstein, D. Arginine homeostasis and transport in the human pathogen Leishmania donovani. J. Biol. Chemistry, J. Biol. Chem. 284, 19800-19807, (2009).

Goldman-Pinkovich, A., Balno, C., Strasser, R., Zeituni-Molad, M., Bendelak, K., Rentsch, D.,  Ephros, M., Wiese, M., Jardim, A., Myler, P.J., Zilberstein, D. An arginine deprivation response pathway is induced in Leishmania during macrophage invasion., PLoS Path, 14, e1005494 (2016).

Pawar, H., Puri, M., Fischer-Weinberger, R., Madhubala, R. and Zilberstein, D. The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania. PLoS NTD, 13: e0007304 (2019).

Goldman-Pinkovich, A., Kannan, S., Nitzan-Koren, R., Puri, M., Bar-Avraham, Y., McDonald, J.A., Sur, A., Zhang, W.-W., Matlashewski, G., Madhubala, R., Myler, P.J. and Zilberstein, D. Sensing Host Arginine Is Essential for Leishmania Parasites’ Intracellular Development. mBio 11: e02023-20 (2020).

Zilberstein, D. and Myler, P.J. Arginine sensing in intracellular parasitism of Leishmania. Curr. Opinion in Microbiol. 64, 41-46 (2021). PubMed PMID: 34592588.

Amino acid transporters (AAPs)

Shaked-Mishan, P., Suter-Grotemeyer, M., Yoel-Almagor, T., Holland, N., Zilberstein, D. and Rentsch, D. Novel high affinity arginine transporter from the human parasitic protozoan Leishmania donovani. Molecular Microbiology 60, 30-38, (2006). PubMed PMID: 16556218.

Inbar, E., Schlisselberg, D., Suter Grotemeyer, M., Rentsch, D. and Zilberstein, D. A versatile proline-alanine transporter in the unicellular pathogen Leishmania donovani regulates amino acid homeostasis and osmotic stress responses. Biochem. J. 449, 555-566, (2013). PubMed PMID: 22994895.

Schlisselberg, D., Mazarib, E., Inbar, E., Rentsch, D., Myler, P. J., Zilberstein, D. Size does matter: 18 amino acids at the N-terminal tip of a neutral amino acid transporter (LdAAP24) in Leishmania determine substrate specificity. Scientific Reports, 5, 16289-16298 (2015). PubMed PMID: 26549185.

Liburkin-Dan, T., Schlisselberg, D., Fischer-Weinberger, R., Pescher, P., Inbar, E., Rentsch, D., Späth, G.F., Myler, P.J. and Zilberstein, D. Stage-specific expression of the proline-alanine transporter in the human pathogen Leishmania. Mol. Biochem. Parasitol. 222, 1-5 (2018). PubMed PMID: 29655799.

Antimony mode of action

Shaked-Mishan, P., Ulrich, N., Ephros. M. and Zilberstein, D. Novel intracellular SbV reducing activity correlates with antimony susceptibility in Leishmania donovani. J. Biol. Chem. 276, 3971-3976, (2001). PubMed PMID: 3365.

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Recent Publications

Fischer-Weinberger, R., Bachmaier, S., Ober, V., Githur, G.B., Dandugudumula, R., Phan, I.A., Almoznino, M., Polatoglou, E., Tsigankov, P., Nitzan Koren, R., Myler, P.J., Boshart, M. and Zilberstein, D. A divergent protein kinase A regulatory subunit essential for morphogenesis of the human pathogen Leishmania. PLoS Pathogens, 20: e1012073 (2024). PubMed PMID: 38551993.

Vargas, D.A., Gregory, D.J., Koren, R.N., Zilberstein, D., Belew, A.T., El-Sayed, N.M., Gómez, M.A. Macrophage metallothioneins participate in the antileishmanial activity of antimonials. Front. Parasitol. 2: 1242727 (2023). PubMed PMID: 38239429.

Dandugudumula R, Fischer-Weinberger R, Zilberstein D. Morphogenesis Dynamics in Leishmania Differentiation. Pathoggens, 11: 952 (2022). PubMed PMID: 36145385

Zilberstein, D. and Myler, P.J. Arginine sensing in intracellular parasitism of Leishmania. Curr. Opinion in Microbiol. 64, 41-46 (2021). PubMed PMID: 34592588.

Zilberstein, D. Lysosome Sensing Is a Key Mechanism in Leishmania Intracellular Development. Front Microbiol 12, 667807 (2021). PubMed PMID: 34025623.

Goldman-Pinkovich, A., Kannan, S., Nitzan-Koren, R., Puri, M., Bar-Avraham, Y., McDonald, J.A., Sur, A., Zhang, W.-W., Matlashewski, G., Madhubala, R., Myler, P.J. and Zilberstein, D. Sensing Host Arginine Is Essential for Leishmania Parasites’ Intracellular Development. mBio 11: e02023-20 (2020).

Zilberstein, D. and Nitzan Koren, R. Host-Free Systems for Differentiation of Axenic Leishmania. Meth. Mol. Biol 1971: 1-8 (2019). PubMed PMID: 30980296.

Pawar, H., Puri, M., Fischer-Weinberger, R., Madhubala, R. and Zilberstein, D. The arginine sensing and transport binding sites are distinct in the human pathogen Leishmania. PLoS NTD, 13: e0007304 (2019). PubMed PMID: 31017889

Landfear, S.M. and Zilberstein, D. Sensing What’s Out There – Kinetoplastid Parasites. Trends in Parasitol. Trends Parasitol., 35: 274-277 (2019). PubMed PMID: 30655057.

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