עברית

Prof. Michael Blank

Associate Professor פרופ' חבר
Telephone
072-2644926/7/8
Email
blankmic@gmail.com
Bar-Ilan Email
michael.blank@biu.ac.il
Fields of Interest

Regulation of the chromatin structure and genome stability mediated by the E3 ubiquitin ligase.

Research field
Molecular & Cellular Cancer Biology
CV

Prof. Michael Blank is an associate professor who studies Molecular & Cellular Cancer Biology.

Research

E3 ubiquitin ligases and Cancer

Cancer is a multifaceted disease in which dysregulated gene-expression and other aberrant activities are crucial for neoplastic initiation and progression. One of the major mechanisms that regulates gene function is protein ubiquitination. This modification can impose diverse effects on proteins, ranging from proteolysis to modulation of protein structure, localization and function. Central to this evolutionary conserved pathway are the E3 ubiquitin ligases (E3s), which confer specificity to ubiquitination. Many E3s are encoded by tumor suppressors or oncogenes and make pivotal contribution to the pathogenesis of many cancers. Among the different types of E3s, HECT-type E3 ligases have been significantly less explored. Consequently, our knowledge of their substrates, biological functions and mechanisms of regulation in cancer is quite limited.

Our primary research objective is to delineate the spectrum of biological activities of a HECT-type E3 ligase Smurf2. Recently, we identified Smurf2 as a novel tumor suppressor gene (Blank M et al., Nature Medicine 2012). Our continued interest focuses on understanding the role that Smurf2 plays in the regulation of gene expression and cell growth, DNA damage response and repair, chromatin biology (epigenetics) and genomic integrity — intimately connected processes that are frequently compromised in cancer cells. Using a multidisciplinary approach spanning these areas, we are determined to shed light on the multifaceted role that HECT-type E3 ligases in general and Smurf2 in particular, play in cancer biology. We also will gain insight into the regulatory mechanisms governing Smurf2 biodistribution and functional activities.

Another research goal is to investigate the involvement of other HECT type E3 ligases in tumorigenesis, initially focusing on the NEDD4 protein family, members of which have the same domain organization as Smurf2, and potentially share intracellular substrates and pathways. By extensively studying Smurf2 and its homologues, we hope to learn how these molecules participate in normal and aberrant cellular processes. We believe such knowledge will provide novel targets for therapeutic intervention in cancer treatment.

 

Publications

Research Publications:

  1. Kayyal-Tarabeia I, Michael Y, Lensky IM, Levy I, Blank M, Agay-Shay K. Residential greenness and lower breast and prostate cancer incidence: Evidence from a retrospective cohort study of 977,644 participants from Israel. Sci Total Environ. 918: 170631, 2024.
  2. Kayyal-Tarabeia I, Blank M, Zick A, Agay-Shay K. Residence near industrial complex and cancer incidence: A registry-based cohort of 1,022,637 participants with a follow-up of 21 years, Israel. Environ Res. 216(Pt 1): 114471, 2023.
  3. Kayyal-Tarabeia I, Michael Y, Lensky I, Blank M, Agay-Shay K. Residential greenness and site-specific cancer: A registry-based cohort of 144,427 participants with a 21-years of follow-up, Tel-Aviv district, Israel. Environ Res. 212(Pt C): 113460, 2022.
  4. Koganti P, Kadali VN, Manikoth Ayyathan D, Emanuelli A, Paolini B, Levy-Cohen G, Blank M. The E3 ubiquitin ligase SMURF2 stabilizes RNA editase ADAR1p110 and promotes its adenosine-to-inosine (A-to-I) editing function. Cell Mol Life Sci. 79(5): 237, 1-19, 2022.
  5. Shah PA, Boutros-Suleiman A, Emanuelli A, Paolini B, Levy-Cohen G, Blank M. The Emerging Role of E3 Ubiquitin Ligase SMURF2 in the Regulation of Transcriptional Co-Repressor KAP1 in Untransformed and Cancer Cells and Tissues. Cancers. 14 (7): 1607, 1-20, 2022.
  6. Ilić N, Tao Y, Boutros-Suleiman S, Kadali VN, Emanuelli A, Levy-Cohen G, Blank M. SMURF2-mediated ubiquitin signaling plays an essential role in PARP1 PARylating activity, molecular interactions and functions in mammalian cells. FASEB J. 35: e21436, 1-20, 2021.
  7. Manikoth Ayyathan D, Levy-Cohen G, Shubely M, Boutros-Suleiman S, Lepechkin-Zilbermintz V, Shokhen M, Albeck A, Gruzman A, Blank M. Development and characterization of SMURF2-targeting modifiers. J Enzyme Inhib Med Chem. 36(1): 401-409, 2021.
  8. Manikoth Ayyathan D, Koganti P, Marcu-Malina V, Litmanovitch T, Trakhtenbrot L, Emanuelli A, Apel-Sarid L, Blank M. SMURF2 prevents detrimental changes to chromatin, protecting human dermal fibroblasts from chromosomal instability and tumorigenesis. Oncogene. 39: 3396-3410, 2020.
  9. Blank M. Targeted Regulation of Nuclear lamins by Ubiquitin and Ubiquitin-Like Modifiers. Cells. 9 (6): 1340, 1-13, 2020.
  10. Emanuelli A, Manikoth Ayyathan D, Koganti P, Shah PA, Apel-Sarid L, Paolini B, Detroja R, Frenkel-Morgenstern M, Blank M. Altered expression and localization of tumor suppressive E3 ubiquitin ligase SMURF2 in human prostate and breast cancer. Cancers. 11(4): 556, 1-16, 2019.
  11. Koganti P, Levy-Cohen G, Blank M. Smurfs in Protein Homeostasis, Signaling, and Cancer. Front Oncology. 8: 295, 1-11, 2018.
  12. Borroni AP, Emanuelli A, Shah PA, Ilić N, Apel-Sarid L, Paolini B, Manikoth Ayyathan D, Koganti P, Levy-Cohen G, Blank M. Smurf2 regulates stability and the autophagic-lysosomal turnover of lamin A and its disease-associated from progerin. Aging Cell. 17(2): e12732, 1-12, 2018.
  13. Zou X, Blank M. Targeting p38 MAP kinase signaling in cancer through posttranslational modifications. Cancer Lett. 384: 19-26, 2017.
  14. Hausmann M, Ilić N, Pilarczyk G, Logeswaran A, Lee JH, Borroni AP, Krufczik M, Theda F, Waltrich N, Bestvater F, Hildenbrand G, Cremer C, Blank M. Challenges for superresolution localization microscopy and biomolecular fluorescent nano-probing in cancer research. Int J Mol Sci. 18(10): 2066, 1-21, 2017.
  15. Emanuelli A, Borroni AP, Apel-Sarid L, Shah PA, Manikoth Ayyathan D, Koganti P, Levy-Cohen G, Blank M. Smurf2-mediated stabilization of DNA topoisomerase IIα controls genomic integrity. Cancer Res. 77(16): 4217-4227, 2017.
  16. Manikoth Ayyathan D, Ilic N, Gil-Henn H, Blank M. Generation of SMURF2 knockout human cells using the CRISPR/Cas9 system. Analytical Biochem. 531: 56-59, 2017.
  17. Zou X, Levy-Cohen G, Blank M. Molecular functions of NEDD4 E3 ubiquitin ligases in cancer. Biochim Biophys Acta. 1856: 91-106, 2015.
  18. Levy-Cohen G, Blank M. Functional analysis of protein ubiquitination. Analytical Biochem. 484: 37-39, 2015.
  19. Meir M, Galanty Y, Kashani L, Blank M, Fernández-Ávila MJ, Andres Cruz-Garcia A, Star A, Shochot L, Thomas Y, Garrett LJ, Chamovitz D, Bodine DM, Kurz T, Huertas P, Ziv Y, Shiloh Y. The COP9 signalosome is vital for timely repair of DNA double-strand breaks. Nucleic Acids Res. 43(9): 4517-4530, 2015. 
  20. Zhao X, Parpart S, Takai A, Roessler S, Budhu A, Yu Z, Blank M, Zhang YE, Jia HL,Ye QH, Qin LX, Tang ZY, Thorgeirsson SS, Wang XW. Integrative genomics identifies YY1AP1 as an oncogenic driver in EpCAM+ AFP+hepatocellular Carcinoma. Oncogene. 34(39): 5095-5104, 2015.
  21. Blank M, Tang Y, Yamashita M, Burkett SS, Cheng S, Zhang YE. A tumor suppressor function of Smurf2 associated with controlling chromatin landscape and genome stability through RNF20. Nature Med. 18(2): 227-234, 2012.
  22. Lavie G, Barliya T, Mandel M, Blank M, Ron Y, Orenstein A, Livnat T, Friedman N, Weiner L, Sheves M, Weinberger D. "Competitive quenching": a mechanism by which perihydroxylated perylenequinone photosensitizers can prevent adverse phototoxic damage caused by verteporfin during photodynamic therapy. Photochem Photobiol. 83(5): 1270-1277, 2007.
  23. Blank M, Shiloh Y. Programs for cell death: apoptosis is only one way to go. Cell Cycle. 6: 686-695, 2007.
  24. Burov SV, Iablokova TV, Dorosh M, Shkarubskaia ZP, Blank M, Epshtein N, Fridkin M. Luliberin analogues exhibiting a cytotoxic effect on tumor cells in vitro. Bioorg Khim. 32: 449-466, 2006.
  25. Blank M, Lerenthal Y, Mittelman L, Shiloh Y. Condensin I recruitment and uneven chromatin condensation precede mitotic cell death in response to DNA damage. J Cell Biol. 174: 195-206, 2006.
  26. Hazan S, Lavie G, Blank M, Mandel M, Grunbaum A, Meruelo D, Solomon A. Anti-angiogenic activities of hypericin in vivo: Potential for ophthalmologic applications. Angiogenesis. 8: 35-42, 2005.
  27. Weinberger D, Ron Y, Lusky M, Gaaton D, Orenstein A, Blank M, Mandel M, Livnat T, Barliya T, Lavie G. Competitive quenching: a possible novel approach in protecting RPE cells from damage during PDT. Curr Eye Res. 30: 269-277, 2005.
  28. Blank M, Lavie G, Mandel M, Hazan S, Orenstein A, Keisari Y. Antimetastatic activity of the photodynamic agent hypericin in the dark. Int J Cancer. 111: 596-603, 2004.
  29. Blank M, Mandel M, Keisari Y, Meruelo D, Lavie G. Enhanced Hsp90 ubiquitinylation as a potential mechanism for mitotic cell death in cancer cells induced with hypericin.  Cancer Res. 63: 8241-8247, 2003.
  30. Blank M, Kostenich G, Kimel S, Lavie G, Keisari Y, Orenstein A. Wavelength Dependent Properties of Photodynamic Therapy Using Hypericin in vitro and in an Animal Model. Photochem Photobiol. 76: 335-340, 2002.
  31. Blank M, Mandel M, Hazan S, Keisari Y, Lavie G. Anti-cancer activities of hypericin in the dark. Photochem Photobiol. 74: 120-125, 2001.
  32. Blank M, Lavie G, Mandel M, Keisari Y. Effects of photodynamic therapy with hypericin in mice bearing highly invasive solid tumors. Oncol Res. 12: 409-418, 2001.

Last Updated Date : 21/02/2024