Prof. Carmit Levy

Associate Professor, Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine

microRNA and DICER in Differentiation and Malignant Transformation of Melanocytes

Our scientific interests involve the role of microRNAs in development, differentiation and malignant transformation. Focusing our studies on melanocytes will provide the foundation for developing novel approaches in the prevention, diagnosis, and treatment of skin cancer in general and melanoma in particular. In addition, we are intrigued by the possibility of using these systems as a model for exploring basic microRNA biogenesis beyond the cell specific context.

Publications

Golan, T., and Levy, C. (2019) Negative Regulatory Loop between Microphthalmia-Associated Transcription Factor (MITF) and Notch Signaling. Int J Mol Sci 20

Malcov-Brog, H., Alpert, A., Golan, T., Parikh, S., Nordlinger, A., Netti, F., Sheinboim, D., Dror, I., Thomas, L., Cosson, C., Gonen, P., Stanevsky, Y., Brenner, R., Perluk, T., Frand, J., Elgavish, S., Nevo, Y., Rahat, D., Tabach, Y., Khaled, M., Shen-Orr, S. S., and Levy, C. (2018) UV-Protection Timer Controls Linkage between Stress and Pigmentation Skin Protection Systems. Mol Cell 72, 444-456 e447

Nordlinger, A., Dror, S., Elkahloun, A., Del Rio, J., Stubbs, E., Golan, T., Malcov, H., Pricket, T. D., Cronin, J. C., Parikh, S., Labes, S., Thomas, L., Yankovitz, G., Tabach, Y., Levy, C., Samuels, Y., and Khaled, M. (2018) Mutated MITF-E87R in Melanoma Enhances Tumor Progression via S100A4. J Invest Dermatol 138, 2216-2223

Amar, D., Vizel, A., Levy, C., and Shamir, R. (2018) ADEPTUS: a discovery tool for disease prediction, enrichment and network analysis based on profiles from many diseases. Bioinformatics 34, 1959-1961

Sheinboim, D., Maza, I., Dror, I., Parikh, S., Krupalnik, V., Bell, R. E., Zviran, A., Suita, Y., Hakim, O., Mandel-Gutfreund, Y., Khaled, M., Hanna, J. H., and Levy, C. (2017) OCT4 impedes cell fate redirection by the melanocyte lineage master regulator MITF in mouse ESCs. Nat Commun 8, 1022

Dror, S., Sander, L., Schwartz, H., Sheinboim, D., Barzilai, A., Dishon, Y., Apcher, S., Golan, T., Greenberger, S., Barshack, I., Malcov, H., Zilberberg, A., Levin, L., Nessling, M., Friedmann, Y., Igras, V., Barzilay, O., Vaknine, H., Brenner, R., Zinger, A., Schroeder, A., Gonen, P., Khaled, M., Erez, N., Hoheisel, J. D., and Levy, C. (2016) Melanoma miRNA trafficking controls tumour primary niche formation. Nat Cell Biol 18, 1006-1017

Levin, L., Srour, S., Gartner, J., Kapitansky, O., Qutob, N., Dror, S., Golan, T., Dayan, R., Brener, R., Ziv, T., Khaled, M., Schueler-Furman, O., Samuels, Y., and Levy, C. (2016) Parkin Somatic Mutations Link Melanoma and Parkinson's Disease. J Genet Genomics 43, 369-379

Golan, T., Messer, A. R., Amitai-Lange, A., Melamed, Z., Ohana, R., Bell, R. E., Kapitansky, O., Lerman, G., Greenberger, S., Khaled, M., Amar, N., Albrengues, J., Gaggioli, C., Gonen, P., Tabach, Y., Sprinzak, D., Shalom-Feuerstein, R., and Levy, C. (2015) Interactions of Melanoma Cells with Distal Keratinocytes Trigger Metastasis via Notch Signaling Inhibition of MITF. Mol Cell 59, 664-676

Bell, R. E., Golan, T., Sheinboim, D., Malcov, H., Amar, D., Salamon, A., Liron, T., Gelfman, S., Gabet, Y., Shamir, R., and Levy, C. (2016) Enhancer methylation dynamics contribute to cancer plasticity and patient mortality. Genome Res 26, 601-611

Dror, I., Golan, T., Levy, C., Rohs, R., and Mandel-Gutfreund, Y. (2015) A widespread role of the motif environment in transcription factor binding across diverse protein families. Genome Res 25, 1268-1280

Melamed, Z., Levy, A., Ashwal-Fluss, R., Lev-Maor, G., Mekahel, K., Atias, N., Gilad, S., Sharan, R., Levy, C., Kadener, S., and Ast, G. (2013) Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions. Mol Cell 50, 869-881

Bell RE, Khaled M, Netanely D, Schubert S, Golan T, Buxbaum A, Janas MM, Postolsky B, Shamir R, Levy C*. Transcription factor/microRNA axis blocks melanoma adhesion program by miR-211 targeting NUAK1. J Invest Dermatol, 134:441-512013. 2014.

Tabach Y, Golan T, Hernández-Hernández A, Messer AR, Fukuda T, Kouznetsova A, Liu J-G, Lilienthal I, Levy C*, Ruvkun G*. Human disease locus discovery and mapping to molecular pathways through phylogenetic profiling. Mol Syst Biol, 9:692. 2013.

Shaham O, Gueta K, Mor E, Oren-Giladi P, Grinberg D, Xie Q, Cvekl A, Shomron N, Davis N, Keydar- Prizant M, Raviv S, Pasmanik-Chor M, Bell R, Levy C, Avellino R, Banfi S, Conte I, Ashery-Padan R. Pax6 regulates gene expression in the vertebrate lens through miR-204. PLoS Genet, 9:e1003357. 2013.

Melamed Z, Levy A, Ashwal-Fluss R, Lev-Maor G, Mekahel K, Atias N, Gilad S, Sharan R, Levy C, Kadener S*, Ast G*. Alternative splicing regulates biogenesis of miRNAs located across exon-intron junctions. Mol Cell 50: 869-881, 2013.

Feige E, Yokoyama S, Levy C, Khaled M, Igras V, Richard J. Lin, Lee S, Widlund HR, Scott R. Granter, Andrew L. Kung, Fisher DE. Hypoxia-induced transcriptional repression of the melanoma oncogene MITF by the HIF1-DEC1 axis. Proc Natl Acad Sci USA 108:E924-933, 2011.

Janas MM, Khaled M, Schubert S, Bernstein JG, Golan D, Veguilla RA, Fisher DE, Shomron N, Levy C*, Novina CD*. Feed forward microprocessor and splicing at microRNA intron PLoS Genet. 7:e1002330, 2011.

Levy C, Mehdi Khaled, Dimitrios Iliopoulos, Maja Janas, Steffen Schubert, Sophie Pinner, Po-Hao Chen, Shuqiang Li, Anne Fletcher, Satoru Yokoyama, Kenneth L. Scott, Levi A. Garraway, Jun S. Song, Scott R. Granter, Shannon J. Turley, David E. Fisher, and Carl D. Novina, Intronic miR-211 assumes the tumor suppressive function of its host gene in melanoma. Mol Cell 40:841-849, 2010. (ranked “must read” on F1000 list; covered in News and Views of Pigm Cell Melan Res)

Khaled M, Levy C and Fisher D.E, Control of melanocyte differentiation by a MITF-PDE4d3 homeostatic circuit. Genes & Dev 24:2276-2281, 2010. (covered in News and Views of Pigm Cell Melan Res).

Levy C, Khaled M, Robinson K.C, Veguilla R.A, Chen PH, Yokoyama S, Makino E, Jun Lu, Larue L, Beermann F, Chin L, Bosenberg M, Song J.S, and Fisher D.E, Lineage specific transcriptional regulation of DICER by MITF in melanocytes, Cell 141:994-1005, 2010. (covered in News and Views of Pigm Cell Melan Res).

Levy C, Golan D, Friedman B and Shomron N. Biased hosting of intronic microRNA genes. Bioinformatics. 26:992-995, 2010.

Reviews

Bell RE, Levy C. The 3 M’s: Melanoma, MITF and microRNA. Pigment Cell Melanoma Res 24:1088-1106, 2011.

Shomron N and Levy C. MicroRNA-Biogenesis and Pre-mRNA Splicing Crosstalk. J Biomed Biotech. 2009:594678, 2009.

Levy C, and Fisher D.E, Dual role of lineage restricted transcription factors. Transcription 2:19-22, 2011.

Awards