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Pablo Kizelsztein, Postdoctoral Associate

Postdoctoral Studies

  • My project was the establishment of animal models of neurodegenerative diseases (EAE-Multiple Sclerosis) and the production of liposomes containing antioxidants in order to treat these pathological situations. During my Post Doc I gained experience in the estasblishment of in vivo models (EAE), preparation and characterization of liposomes as well as pharmacokinetic and biodistributions studies.

  • Part of the results were published in a patent (FORMULATIONS COMPRISING AN AMPHIPATHIC WEAK BASE FOR TREATMENT OF NEURODEGENERATIVE CONDITIONS) and also papers are in preparation.

Industry Experience

  • As a project manager in QBI, I was in charge of the development of a novel in vitro neuronal system to express the candidate genes found to be involved in stroke.
    The development of the P19 embryonic carcinoma cell line included:

    • Establishment of growth conditions including medium and serum optimization of the undifferentiated and differentiated cell line.
    • Characterization of the P19 neuronal system by western blot in order to determine the percentage of neurons and glia in the cultures.
    • Establishment of a cell proliferation assay (Alamar blue) for differentiated neurons that can be adapted to HTS (high throughpout screening) in the company.
    • Establishment of an inducible system in P19 neurons in order to express in a controlled manner our cytotoxic genes.
    • Establishment of the RNAi method in P19 and other cell lines in order to determine loss of function of our candidate genes in the respective cell lines.
    • Development of a cytotoxic assay in primary neuronal cell cultures and P19 differentiated neurons in order to test in vitro toxicity of a novel lead candidate.
    • Establishment, planning and management of a preliminary in vivo toxicity study of a novel lead compound administered to mice.

Ph. D. – Weizmann Institute of Science

  • The topic of my thesis was the mechanism of activation and desensitization of the AMPA glutamate receptors.

  • Ionotropic glutamate receptors (iGluRs) mediate excitatory synaptic transmission in vertebrates and invertebrates through ligand-induced opening of membrane-embedded receptor channels. These receptors play a crucial role in the development and function of the nervous system, are involved in memory and learning, and are implicated in neurological dysfunctions such as Alzheimer’s, Parkinson’s and Huntington’s disease, schizophrenia, epilepsy, Rasmmusen’s encephalitis and stroke.

  • My Ph. D. work has been devoted to studies aiming at an understanding of the molecular mechanisms of activation and desensitization of the AMPA receptor GluR1 and the dependence of this processes on the nature of the agonist. The understanding of this mechanism is of extreme importance as it mat contribute to the development of new and better glutamatergic ligands that will affect the pathological conditions in which the ionotropic glutamate receptors are involved.

  • During my Ph.D. studies I gained background and experience in biochemistry, molecular and cell biology, electrophysiology and pharmacology. Prior to my doctoral studies I completed a M.Sc. at the Department of Human Microbiology in the Sackler School of Medicine in Tel Aviv. My thesis topic was the purification of a small GTP binding protein involved in the activation of the NADPH oxidase enzyme complex of the macrophages. Here I gained experience in HPLC purification of proteins, SDS-PAGE and in preparation of polyclonal antibodies.

Publications

  1. Pablo Kizelsztein, and Ilya Raskin. Method of Treating Demyelinating CNS Diseases. US patent application 20100104675, 2010.

  2. Kizelsztein, P., Govorko, D., Komarnytsky, S., Evans, E., Wang, Zh., Cefalu, W. T., and Raskin, I. 20-Hydroxyecdysone decreases weight and hyperglycemia in a diet-induced obesity mice model. American Journal of Physiology – Endocrinology and Metabolism, Vol. 296, No. 3, pp. E433-E439, 2009.

  3. Veronica Wasserman*, Pablo Kizelsztein*, Olga Garbuzenko, Rony Kohen, Haim Ovadia, Rinat Tabakman and Yechezkel Barenholz. The antioxidant Tempamine: In Vitro Antitumor and Neuroprotective Effects and Optimization of Liposomal Encapsulation and Release. Langmuir, 23(4): 1937-1947, 2007.
    • * – Equal contribution authors.

  4. Pablo Kizelsztein, Haim Ovadia, Olga Garbuzenko, Alexander Sigal and Yechezquel Barenholz. Tempamine: An amphipathic weak base encapsulated in stable stabilized liposome crosses the blood brain barrier and ameliorates experimental autoimmune encephalomyelitis. In preparation.

  5. Strutz, N., Villmann, C., Breitinger, H. G., Werner, M., Wenthold, R. J., Kizelsztein, P., Teichberg, V. I., and Hollmann, M. Kainate binding proteins (KBPs) are rendered functional ion channels upon transplantation of two short pore-flanking domains from a kainate receptor (2002). J. Biol. Chem. 277 (50) 48035-42

  6. Strutz, N., Villmann, C., Thalhammer, A., Kizelsztein, P., Eisenstein, M., Teichberg, V. I. and Hollmann, M. Localization of Domains and Amino Acids Involved in GluR7 Ion Channel Function (2001). J. Neurosci. 21 (2), 401-11

  7. Kizelsztein, P., Eisenstein, M., Strutz, R., Hollmann, M. and Teichberg, V. I. Mutant cycle analysis of the active and desensitized states of an AMPA receptor induced by Willardiines (2000). Biochemistry 39 (42), 12819-12827.

  8. Kizelsztein, P., Eisenstein, M., Strutz, R., Hollmann, M. and Teichberg, V.I. Analysis at atomic resololution of the activated and desensitized state of an AMPA receptor induced by Willardiines (1999). Neurosci. Letters 54, S24 (abstract).

  9. Everts, I., Petroski, R., Kizelsztein, P., Teichberg, V. I., Heinemann, S. F. and Hollmann, M. (1999). Lectin-induced inhibition of desensitization of the kainate receptor GluR6 depends on the activation state and can be mediated by a single native or ectopic N-linked carbohydrate side chain. J. Neurosci. 19 (3), 916-27

  10. Kizelsztein, P., and Teichberg, V. I. (1998). Binding site docking of willardiines in the activation and desensitization of the GluR1 subtype of AMPA receptors. Neurosci. Letters 51, S22 (abstract).

Participation at professionals meetings:

  • January 2006:
    • Best student abstract award selected for oral presentation in the
      Annual meeting of the Israel Society for Free Radical Research at Ben-Gurion University of the Negev. “Treatment of neurodegenerative diseases by antioxidant loaded sterically stabilized liposomes”.

  • October 2004:
    • Poster presentation in a workshop entitled “Brain uptake and utilization of fatty acids, lipids and lipoproteins” (applications to neurological disorders), Bethesda – Maryland.

  • September 2004:
    • Poster presentation in the 5th Annual meeting of the Israeli chapter of controlled release society (ICRS).

  • March 2001:
    • Participation in the American College of Cardiology (ACC 50) Annual Scientific Session Orlando, Florida.

  • December 2000:
    • Poster presentation at the Israeli Society for Neuroscience meeting in Eilat, Israel.
  • December 1998:
    • Participant at the annual meeting of the Israeli Society for Neuroscience.
  • November 1998:
    • Poster presentation in a workshop entitled “Structure and Function of Ion Channels”, in Madrid, Spain.

Technical Skills

  • Receptor binding assays, protein purification, enzyme assays, HPLC, SDS-PAGE, Western blotting, preparation of polyclonal antibodies, expression of genes in mammalian cells in culture, neuronal cell culture, Xenopus oocyte analysis, electrophysiology, two electrode voltage clamp measurements, recombinant DNA techniques, site-directed mutagenesis and protein expression in E. coli, bioinformatics and biomedical analysis. In vivo toxicological studies, pharmacokinetic and biodistribution in animal studies.

Computer Skills

  • Microsoft Office applications (Word, Excel, PowerPoint), Photoshop, Canvas, PS8 project management software, SigmaPlot, Cricketgraph, Prisma Graphpad software. Macintosh and PC proficient.