Ph.D.: Weizmann Institute of Science, Israel
Post-doctorate: Stanford University, USA
Position: Senior Lecturer
Department of Microbiology, Immunology and Genetics
Faculty of Health Sciences
Lysine methylation signaling and epigenetics
The goal of our research is to understand how intercellular signaling networks regulate oncogenic and cell differentiation processes through epigenetic mechanisms and how dysregulation of these pathways leads to disease.
Our work centers on the biology of protein lysine methylation, a post-translational modification that plays a key role in directing cellular and epigenetic programs. Lysine methylation catalyzed by protein lysine methyltransferases (PKMTs) is severely dysregulated in numerous diseases. Given the reversible nature of this chemical modification, targeting lysine methylation holds significant therapeutic promise.
Despite the key role lysine methylation serves in modulating a wide range of signaling pathways, the catalytic activity and substrate specificity of the majority of PKMT enzymes remains unknown. Furthermore, relatively few protein lysine methylation substrates have been identified and functionally characterized.
In our laboratory, we are utilizing a multi-disciplinary biochemical, molecular, cellu¬lar, proteomic and genomic approaches to address fundamental questions at the intersection between chromatin biology and cell signaling. We aim to elucidate the molecular mechanisms, physiological and pathological functions of PKMTs and lysine methylation biology.
1. To identify new methylation events of histone and non-histone proteins and to define the molecular mechanisms by which these methyl marks are generated and transduced and to unravel the biological functions of such methylation events.
2. To define the role of lysine methylation in the modulation of a variety of biological processes and disease models, with a focus on oncogenic and cell differentiation processes.
3. To further develop peptide and protein microarrays technologies focusing on protein lysine methylation.
4. To develop anti-cancer peptide inhibitors to target the enzymatic activity of protein-lysine methyltransferases.
Levy D., Adamovich Y., Reuven N. and Shaul Y. (2008). Yap1 phosphorylation by c-Abl is a critical step in selective activation of pro-apoptotic genes in response to DNA damage. Molecular Cell 29(3):350-361.
Levy D. and Gozani O. (2010). Decoding chromatin goes high tech. Cell 142(6):844-846.
Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson U., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung C., Chua K.F., Utz P.J., Shi X., Prinjha R.K., Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X. and Gozani O. (2011). SETD6 lysine methylation of RelA couples GLP activity at chromatin to tonic repression of NF-kB signaling. Nature Immunology 12(1):29-36.
Chang Y., Levy D., Horton J.R., Peng J., Zhang X., Gozani O. and Cheng X. (2011). Structural basis of SETD6-mediated regulation of the NF-kB network via methyl-lysine signaling. Nucleic Acids Res. 39(15): 6380-6389.
Levy D., Liu C.L., Yang Z., Newman A.M., Alizadeh A.A., Utz P.J.# and Gozani O.# (2011). A proteomic approach for the identification of novel lysine methyltransferase substrates. Epigenetics & Chromatin 4(1):19. #Correspondence authors
Price J.V, Tangsombatvisit S., Xu G., Yu J., Levy D., Baechler E.C., Gozani O., Varma M., Utz P.J. and Liu C.L. (2012). On silico peptide microarrays for high resolution mapping of antibody epitopes and diverse protein-protein interactions. Nature Medicine 18:1434-1440.