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Levkowitz, Gil
Email: gil.levkowitz@weizmann.ac.il
URL: http://www.weizmann.ac.il/mcb/GLevkowitz/
Affiliation: Levkowitz Lab
Address: The Weizmann Institute of Science Department of Molecular Cell Biology 234 Herzl St. Rehovot, 76100 Israel
Country: Israel
Phone: 972-8-934-6077
Fax: 972-8-934-4125
ORCID ID: 0000-0002-3896-1881


BIOGRAPHY AND RESEARCH INTERESTS
Gil Levkowitz received his BSc. and MSc. from Tel Aviv University in Israel. He conducted his Ph.D. research in Prof. Yosef Yarden’s laboratory at the Weizmann Institute of Science focusing on epidermal growth factor receptor (EGFR) signaling, and earned his Ph.D. degree at 2000. He was a Post-Doctoral Fellow (2000-2002) in Arnon Rosenthal’s laboratory at Genentech Inc., (South San Francisco, USA) where he studied the embryonic development of the dopamine- secreting [termed ‘dopaminergic’] neuronal cell type, which is associated with Parkinson’s disease as well as other neurological disorders. He then spent approximately two years (2002-2003) as a project team leader at Rinat-Neuroscience Corp. in Palo Alto. USA (now Rinat-Pfizer Inc.), conducting research and pre-clinical development of drugs for Alzheimer’s and Parkinson’s diseases. Since returning to Israel he has been a Senior Scientist and then an Associate Professor at the Weizmann Institute. His lab is using zebrafish to study genetic pathways controlling hypothalamic neuronal circuits that have been associated with neurological conditions such as depression, chronic stress, autism and obesity.


PUBLICATIONS
Ribeiro, D., Nunes, A.R., Teles, M., Anbalagan, S., Blechman, J., Levkowitz, G., Oliveira, R.F. (2020) Genetic variation in the social environment affects behavioral phenotypes of oxytocin receptor mutants in zebrafish. eLIFE. 9:
Biran, J., Gliksberg, M., Shirat, I., Swaminathan, A., Levitas-Djerbi, T., Appelbaum, L., Levkowitz, G. (2020) Splice-specific deficiency of the PTSD-associated gene PAC1 leads to a paradoxical age-dependent stress behavior. Scientific Reports. 10:9559
Nunes, A.R., Carreira, L., Anbalagan, S., Blechman, J., Levkowitz, G., Oliveira, R.F. (2020) Perceptual mechanisms of social affiliation in zebrafish. Scientific Reports. 10:3642
Ribeiro, D., Nunes, A.R., Gligsberg, M., Anbalagan, S., Levkowitz, G., Oliveira, R.F. (2020) Oxytocin receptor signaling modulates novelty recognition but not social preference in zebrafish. Journal of neuroendocrinology. 32(4):e12834
Gordon, L., Blechman, J., Shimoni, E., Gur, D., Anand-Apte, B., Levkowitz, G. (2019) Fenestrae-associated protein Plvap regulates the rate of blood-borne proteins passage into the hypophysis. Development (Cambridge, England). 146(23):
Anbalagan, S., Blechman, J., Gliksberg, M., Gordon, L., Rotkopf, R., Dadosh, T., Shimoni, E., Levkowitz, G. (2019) Robo2 regulates synaptic oxytocin content by affecting actin dynamics. eLIFE. 8:
Denichenko, P., Mogilevsky, M., Cléry, A., Welte, T., Biran, J., Shimshon, O., Barnabas, G.D., Danan-Gotthold, M., Kumar, S., Yavin, E., Levanon, E.Y., Allain, F.H., Geiger, T., Levkowitz, G., Karni, R. (2019) Specific inhibition of splicing factor activity by decoy RNA oligonucleotides. Nature communications. 10:1590
Anbalagan, S., Gordon, L., Blechman, J., Matsuoka, R.L., Rajamannar, P., Wircer, E., Biran, J., Reuveny, A., Leshkowitz, D., Stainier, D.Y.R., Levkowitz, G. (2018) Pituicyte Cues Regulate the Development of Permeable Neuro-Vascular Interfaces. Developmental Cell. 47(6):711-726.e5
Blechman, J., Anbalagan, S., Matthews, G.G., Levkowitz, G. (2018) Genome Editing Reveals Idiosyncrasy of CNGA2 Ion Channel-Directed Antibody Immunoreactivity Toward Oxytocin. Frontiers in cell and developmental biology. 6:117
Gur, D., Nicolas, J.D., Brumfeld, V., Bar-Elli, O., Oron, D., Levkowitz, G. (2018) The Dual Functional Reflecting Iris of the Zebrafish. Advanced science (Weinheim, Baden-Wurttemberg, Germany). 5:1800338
Wircer, E., Blechman, J., Borodovsky, N., Tsoory, M., Nunes, A.R., Oliveira, R.F., Levkowitz, G. (2017) Homeodomain protein Otp affects developmental neuropeptide switching in oxytocin neurons associated with a long-term effect on social behavior. eLIFE. 6
Blechman, J., Levkowitz, G., Gothilf, Y. (2017) The not-so-long history of zebrafish research in Israel. The International journal of developmental biology. 61:149-157
Biran, J., Levkowitz, G. (2016) Zebrafish Reel in Phenotypic Suppressors of Autism. Neuron. 89:673-675
Biran, J., Tahor, M., Wircer, E., Levkowitz, G. (2015) Role of developmental factors in hypothalamic function. Frontiers in Neuroanatomy. 9:47
Blechman, J., and Levkowitz, G. (2013) Alternative Splicing of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1: Mechanisms of Fine Tuning of Brain Activity. Frontiers in neuroscience. 4:55
Gutnick, A., and Levkowitz, G. (2012) The neurohypophysis: fishing for new insights. Journal of neuroendocrinology. 24(6):973-974
Amir-Zilberstein, L., Blechman, J., Sztainberg, Y., Norton, W.H., Reuveny, A., Borodovsky, N., Tahor, M., Bonkowsky, J.L., Bally-Cuif, L., Chen, A., and Levkowitz, G. (2012) Homeodomain protein otp and activity-dependent splicing modulate neuronal adaptation to stress. Neuron. 72(2):279-291
Blechman, J., Amir-Zilberstein, L., Gutnick, A., Ben-Dor, S., and Levkowitz, G. (2011) The Metabolic Regulator PGC-1α Directly Controls the Expression of the Hypothalamic Neuropeptide Oxytocin. The Journal of neuroscience : the official journal of the Society for Neuroscience. 31(42):14835-14840
Gutnick, A., Blechman, J., Kaslin, J., Herwig, L., Belting, H.G., Affolter, M., Bonkowsky, J.L., and Levkowitz, G. (2011) The hypothalamic neuropeptide oxytocin is required for formation of the neurovascular interface of the pituitary. Developmental Cell. 21(4):642-654
Machluf, Y., Gutnick, A., and Levkowitz, G. (2011) Development of the zebrafish hypothalamus. Annals of the New York Academy of Sciences. 1220(1):93-105
Machluf, Y., and Levkowitz, G. (2011) Visualization of mRNA Expression in the Zebrafish Embryo. Methods in molecular biology (Clifton, N.J.). 714:83-102
Russek-Blum, N., Nabel-Rosen, H., and Levkowitz, G. (2010) Two-photon-based photoactivation in live zebrafish embryos. Journal of visualized experiments : JoVE. (46)
Palevitch, O., Abraham, E., Borodovsky, N., Levkowitz, G., Zohar, Y., and Gothilf, Y. (2010) Cxcl12a-Cxcr4b signaling is important for proper development of the forebrain GnRH system in zebrafish. General and comparative endocrinology. 165(2):262-268
Russek-Blum, N., Nabel-Rosen, H., and Levkowitz, G. (2009) High resolution fate map of the zebrafish diencephalon. Developmental dynamics : an official publication of the American Association of Anatomists. 238(7):1827-1835
Borodovsky, N., Ponomaryov, T., Frenkel, S., and Levkowitz, G. (2009) Neural protein Olig2 acts upstream of the transcriptional regulator sim1 to specify diencephalic dopaminergic neurons. Developmental dynamics : an official publication of the American Association of Anatomists. 238(4):826-834
Palevitch, O., Abraham, E., Borodovsky, N., Levkowitz, G., Zohar, Y., and Gothilf, Y. (2009) Nasal embryonic LHRH factor plays a role in the developmental migration and projection of gonadotropin-releasing hormone 3 neurons in zebrafish. Developmental dynamics : an official publication of the American Association of Anatomists. 238(1):66-75
Russek-Blum, N., Gutnick, A., Nabel-Rosen, H., Blechman, J., Staudt, N., Dorsky, R.I., Houart, C., and Levkowitz, G. (2008) Dopaminergic neuronal cluster size is determined during early forebrain patterning. Development (Cambridge, England). 135(20):3401-3413
Blechman, J., Borodovsky, N., Eisenberg, M., Nabel-Rosen, H., Grimm, J., and Levkowitz, G. (2007) Specification of hypothalamic neurons by dual regulation of the homeodomain protein Orthopedia. Development (Cambridge, England). 134(24):4417-4426
Levkowitz, G., Zeller, J., Sirotkin, H.I., French, D., Schilbach, S., Hashimoto, H., Hibi, M., Talbot, W.S., and Rosenthal, A. (2003) Zinc finger protein too few controls the development of monoaminergic neurons. Nature Neuroscience. 6(1):28-33

NON-ZEBRAFISH PUBLICATIONS
Peer Reviewed Articles:

Chen, Q., Leshkowitz, D. Blechman, J. and G. Levkowitz. 2020. Single-cell molecular and cellular architecture of neurohypophyseal cell types in the adult mouse. eNeuro 7(1): ENEURO.0345-19.2019. https://doi.org/10.1523/ENEURO.0345-19.2019.

Wilcock, D. M., A. Rojiani, A. Rosenthal, G. Levkowitz, S. Subbarao, J. Alamed, D. Wilson, N. Wilson. M. J. Freeman, M. N. Gordon, D. Morgan. 2004, Passive amyloid immunotherapy clears amyloid and transiently activates microglia in a transgenic mouse model of amyloid deposition. 2004. Journal of Neuroscience 24: 6144-6151.

Levkowitz, G., S. Oved, L.N. Klapper, D. Harari,, S. Lavi, M. Sela and Y. Yarden. 2000. c-Cbl is a suppressor of the neu oncogene. Journal of Biological Chemistry 275: 35532-35539.

Levkowitz, G., H. Waterman, S. A. Ettenberg, M. Katz, A. Y. Tysgankov, I. Alroy, S. Lavi, Iwai, K., Y. Reiss, Ciechanover A. and Y. Yarden. 1999. Ubiquitin ligase activity and tyrosine phosphorylation underlie suppression of growth factor signaling by c-Cbl/Sli-1 Molecular Cell 4: 1029-1040.

Watermann, H., G. Levkowitz, I. Alroy and Y. Yarden. 1999. The RING finger of c-Cbl mediates desensitization of the EGF-receptor. J. Biol. Chem. 274: 22151-22154.

Levkowitz, G., H. Waterman, E. Zamir, Z. Kam, S. Oved, W. Y. Langdon, L. Beguinot, B. Geiger and Y. Yarden. 1998. c-Cbl/Sli-1 regulates endocytic sorting and ubiquitination of the epidermal growth factor receptor. Genes & Development 12: 3663-3674.

Tzahar, E., J. D. Moyer, H. Waterman, E. G.Barbacci, J. Bao, G. Levkowitz, M. Shelly, S. Strano, R. Pinkas-Kramarski, J. H.Pierce, G. C. Andrews and Y. Yarden. 1998. Pathogenic poxviruses reveal viral strategies to exploit the ErbB signaling network. EMBO Journal 17: 5948-5963.

Pinkas-Kramarski, R., R. Eilam, I. Alroy, G. Levkowitz, P. Lonai and Y. Yarden. 1997. Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation. Oncogene 15: 2803-2815.

Tzahar, E., R. Pinkas-Kramarski, , J. B. Moyer, L N. Klapper, I. Alroy, G. Levkowitz, M. Shelly, S. Henis, M. Eisenstein, B. J. Radzkin, M. Sela, G. C. Andrews and Y. Yarden. 1997. Bivalency of EGF-like ligands drives the ErbB signaling network. EMBO Journal 16: 4938-4950.

Tzahar, E., H. Waterman, X. Chen, G. Levkowitz, D. Karunagaran, S. Lavi, J. B. Ratzkin, and Y. Yarden. 1996. A hierarchical network of inter- receptor interactions determines signal transduction by Neu Differentiation factor and Epidermal Growth factor. Molecular and Cellular Biology 16: 5276-5287.

Pinkas-Kramarski, R., L. Soussan, H. Waterman, G. Levkowitz, I. Alroy, L. Klapper, S. Lavi, J. B. Ratzkin, M. Sela and Y. Yarden. 1996. Diversification of neu differentiation factor and epidermal growth factor signaling by combinatorial receptor interactions. EMBO Journal 15: 2452-2467.

Chen, X., G. Levkowitz, E. Tzahar, D. Karunagaran, S. Lavi, N. Ben-Baruch, O. Leithner, J. B. Ratzkin, S. S. Bacus and Y. Yarden. 1996. An Immunological approach reveals biological differences between the two NDF receptors, ErbB-3 and ErbB-4. Journal of Biological Chemistry 271: 7620-7629.

Levkowitz, G., L. N. Klapper, E. Tzahar, A. Freywald, M. Sela and Y. Yarden. 1996. Coupling of the c-Cbl proto-oncogene product to ErbB-1/EGF-receptor but not other ErbB proteins. Oncogene 12: 1117-1125.

Dong, Z., A. Brennan, N. Liu, Y. Yarden, G. Levkowitz, R. Mirsky and K. R. Jessen. 1995. Neu differentiation factor is a neuron-glia signal and regulates survival, proliferation, and maturation of rat schwann cell precursors. Neuron 15: 585-596.

Tzahar, E., G. Levkowitz, D. Karunagaran, L. Yi, E. Peles, S. Lavi, D. Chang, N. Liu, A. Yayon, D. Wen and Y. Yarden. 1994. ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all NDF/Heregulin isoforms. Journal of Biological Chemistry 269: 25226-25233.

Berko-Flint, Y., G. Levkowitz and L. Vardimon. 1994. Involvement of c-Jun in the control of glucocorticoid receptor transcriptional activity during development of chicken retinal tissue. EMBO Journal 13: 646-54.

Reviews and Editorials:

Wagner S., Grinevich V. and G. Levkowitz (2020). Advances in Neurohypophysial Hormones Research. Journal of Neuroendocrinology doi.org/10.1111/jne.12853.

Robinson K.J., Bosch O.J., Levkowitz G., Busch K.E., Jarman A. and M.Ludwig. 2019. Social creatures: model animal systems for studying the neuroendocrine mechanisms of social behaviour. Journal of Neuroendocrinology 12:e12807 doi: 10.1111/JNE.12807.

Gliksberg M. and G. Levkowitz. 2017. Smells Familiar: Pheromone-induced neurotransmitter switching mediates social discrimination. Neuron 95:1229-1231. http://dx.doi.org/10.1016/j.neuron.2017.08.044

Blechman J. and G. Levkowitz. 2013. Alternative Splicing of the Pituitary Adenylate Cyclase-Activating Polypeptide Receptor PAC1: Mechanisms of Fine Tuning of Brain Activity. Frontiers in Endocrinology. 4:55. doi:10.3389/fendo.2013.00055.

Gutnick A. and G. Levkowitz. 2012. The neurohypophysis – fishing for new insights. Journal of Neuroendocrinology 24(6):973-974.

Book Chapters:

Biran, J., Wircer, E., Blechman, J. and G. Levkowitz. (2018) Development and function of the zebrafish neuroendocrine system. In Model animals in neuroendocrinology: From worm to mouse to man, M. Ludwig and G. Levkowitz, eds. (Wiley-Blackwell). pp. 101-131. DOI:10.1002/9781119391128.ch5

Edited book: Ludwig M, Levkowitz G. eds. (2018) Model Animals in Neuroendocrinology: From Worm to Mouse to Man. Hoboken, NJ: Wiley Blackwell. ISBN: 978-1-119-39094-7.

Wircer, E., Ben-Dor, S. and G. Levkowitz. 2016. In: Non-mammalian models for neurohypophysial peptides. In Molecular Neuroendocrinology: From Genome to Physiology, D. Murphy and H. Gainer, eds. (Wiley-Blackwell), pp. 301–328. DOI: 10.1002/9781118760369.ch14

Levkowitz, G. and Y. Yarden. 2002. Erbb. In: Wiley Encyclopedia of Molecular Medicine, by John Wiley & Sons, Inc. 5 Vol. Set: 1197-1200.