M. Cohen-Armon - Education and expertise

Associate Professor at the Sackler School of Medicine and Sagol School of Neuroscience at the Tel-Aviv University. The general focus of my research is on signal transduction mechanisms transforming signals in the cell membrane into chromatin remodeling and gene expression.

I received my education in the Technion,( IIT, Israel Institute of Technology, Haifa):B.Sc. in Chemistry (cum laude) and D.Sc. in Biophysics and Electrophysiology (Voltage dependent Sodium Channels). My postdoc training was on Muscarinic Receptors in the brain, in the lab of Prof. M. Sokolovsky, Neurobiochemistry Dept., Life Sciences, Tel-Aviv University.

On 2001 I was a Visiting Researcher in Columbia University NY as a recipient of Human Frontiers fellowship (HFSP) on molecular mechanisms underlying long-term memory, in the lab of Prof. James Schwartz, I author articles in leading journals, editor and reviewer in several scientific journals, and the inventor of granted patents.

INVENTOR OF PATENTS,

“Breast cancer therapy”: Submitted by Ramot – Tel Aviv University. WO2009/047752 Granted on May 22, 2013, EP2207548B1 (UK, Germany,  France).

"Cancer therapy" granted on April 20, 2014 US 8,729,080 B2

Continuation in part submitted, Pub. No. : US 2014/0303201 A1,  granted Nov 2016 US 9,486,449 B2.

"Treatment of addiction" US patent application 13/761,761 granted Oct 17, 2014 US 08889707B1

MEMBERSHIP IN PROFESSIONAL SOCIETIES

Member, American Chemistry Association, Society of Neuroscience, Society of Biochemistry and Molecular Biology The Israel Society for Neuroscience, The Israeli Society for Biochemistry and Molecular Biology, HFSP- Human Frontiers

RESEARCH TOPICS

Signal transduction mechanisms required for long-term memory formation during learning. The general focus of our research is on signal transduction mechanisms inducing modifications of chromatin-bound proteins, mainly PARP (polyADP-ribose polymerase) proteins. Recently we discovered a new signaling mechanism governed by synergistic activity of phosphorylated Erk and PARP1. This mechanism underlies the long-lasting activity of phosphorylated Erk in the nucleus, and causes chromatin remodeling implicated in synaptic plasticity, Ca-signaling and epigenetic processes. We found that this mechanism underlies the dependence of LTP and long-term memory formation in a variety of animal models on PARP1 activation. This project was funded by ISF grants, Israel Ministry of Health and Neurobiology Funds.

PARP1 activation mediates addiction.Recently we found that the application of PARP1 inhibitors prevents persistent compulsive behaviors as addiction and post-traumatic stress disorders (PTSD). We are currently engaged in collaborative projects on cocaine addiction and alcohol abuse. This project was granted by NIH.

Cancer targeting therapy. Recently we found a novel mechanism eradicating human cancer cells. In this mechanism  quiescent and proliferating normal cells are protected from cell death. However, human cancer cells are efficiently eradicated during abnormal mitosis . Cancer cells resistant to currently used chemotherapy were eradicated . This molecule interferes with multi-centrosomes bi-polar clustering and spindle formation, causing cell-cycle arrest and Mitotic Catastrophe cell death. Thus, the higher is cancer cell proliferating, the more efficient it is eradicated. This exclusive cytotoxic activity  in cancer cells is now under investigation, in an attempt to offer a new cancer-targeting therapy suitable for a wide range of human cancers.  This project was funded by the ICRF, RAMOT-Tel-Aviv University joint with Sheba Medical Center and by Research grants of Novartis.  

ACADEMIC EDITOR:

PLOS ONE ; Am. J. Alzheimer's Disease & Other Dementias ;Signal Transduction Insights.

INVENTOR in PATENTS,
“Breast cancer therapy”: Submitted by Ramot – Tel Aviv University. WO2009/047752 Granted on May 22, 2013, EP2207548B1 (UK, Germany and France).
"Cancer therapy" granted on April 20, 2014 US 8,729,080 B2
Continuation in part submitted, Pub. No. : US 2014/0303201 A1, Pub. Date: Oct. 9, 2014. Granted Aug 2016.
"Treatment of addiction" US patent application 13/761,761 granted Oct 17, 2014 US 08889707B1

MEMBERSHIP IN PROFESSIONAL SOCIETIES
Member, American Chemistry Association, Society of Neuroscience, Society of Biochemistry and Molecular Biology The Israel Society for Neuroscience, The Israeli Society for Biochemistry and Molecular Biology, HFSP- Human Frontiers

 COLLABORATIONS

Prof. Alexander Burkle, Konstanz University, Konstanz, Germany: Signals activating the
nuclear protein PARP-1, physiological and pathological aspects (Kurt Lion
Foundation)
Dr. Segev Barak, Tel-Aviv University. The role of polyADP-ribosylation in alcohol addiction
Dr. Alexander Biro, Nephrology, Wolfson Medical Center: The role of polyADP-ribosylation in
Nephropathy
Dr. Bar-Shira Maymon Batia, Tel-Aviv Medical Center: The role of polyADP-ribosylation in
Fertility
Prof. Joav Chapman, Head Dept. of Neurology, Sheba Medical Center. Role of PARP-1
antibodies in Lupus disease.
Dr. Francoise Dantzer, Biotechnological Institute, Strasbourg, France: Activation of
PARP-1 by ERK
Dr. Gilbert de Murcia, Biotechnological Institute, Strasbourg, France: Activation of
PARP-1 by ERK
Prof Haim Garty, Weizmann Institute of Science The mutual effects of voltage dependent Na
Channels, G-proteins and the muscarinic receptors
Prof. Illana Gozes, Tel-Aviv University: PolyADP-ribosylation mediaties memory
formation in trained mice
Dr. Nava Moran, Faculty of Agriculture, Hebrew University: PolyADP-ribosylation in
circadian clocks in plants.
Prof. Esther Priel, Ben-Gurion University: PolyADP-ribosylation of topoisomerases,
Prof. Asher Shainberg, Bar-Ilan University: Involvement of polyADP-ribosylation in
pathological events of cardiomyocytes.
Prof. Nava Zisapel, Tel-Aviv University. The role of polyADP-ribosylation in memory
formation.
Prof. Jimmy H. Schwartz, Columbia University, NY: My former collaborator on the
role of polyADP-ribosylation in memory formation
Prof. Rony Seger, Weizmann Institute of Science: Activation of PARP-1 by MAP
kinases.
Prof Susan Smith, NYU, Tankyrase inhibitors in cancer therapy.
Prof. Mori Sokolovsky, The mutual effects of ionic channels G-proteins and the muscarinic
receptors
Prof. Gal Yadid, Bar Ilan University, The role of PARP1 in addiction to cocaine

SELECTED PUBLICATIONS

Cohen-Armon, M., Kloog, Y., Henis, Y.I. and Sokolovsky, M. (1985)Batrachotoxin changes the properties of muscarinic receptor in rat brain      and heart: Possible interaction between muscarinic receptor and sodium channel. Proc. Natl. Acad. Sci. USA 82:3524-3527.

Sokolovsky, M., Cohen-Armon, M., Egozi, Y., Guwitz, D., Henis, Y.I.,Kloog, Y., Moscona-Amir, E. Schreiber, G. (1986) Modulation of muscarinic receptors and their interactions.Trends in Pharmacol. Sci. 7:39-44.Cohen-Armon, M. and Sokolovsky, M. (1986) Interactions between the muscarinic receptors, sodium channels and guanine nucleotide-binding protein(s) in rat atria. J. Biol. Chem. 261:12498-12505.

Cohen-Armon, M., Garty, H. Sokolovsky, M. (1988) G-protein mediates voltage regulated interaction of muscarinic receptors with Na-channels. Biochemistry –US 27: 368-374.

Sokolovsky, M. and Cohen-Armon, M.,(1988) Muscarinic receptors, Na -channels and G-protein(s): Interaction in rat membrane preparations and in synaptoneurosomes. In: Recent Advances in Receptor Chemistry (C. Melchiorre
and M. Giannella eds.) Elsevier Science Publishers B.V.Amsterdam.

Sokolovsky, M., and Cohen-Armon, M. (1988) Cross-talk between receptors: Muscarinic receptors, sodium channel and guanine nucleotides binding proteins in rat membrane preparation and synaptoneurosomes. In: Advances in Second Messengers and Phosphoprotein Research, 21 (Adelstein, R., Klee, C. and Rodbell, M., eds. ) Raven Press ltd. New York

Cohen-Armon, M., Sokolovsky, M. and Dascal, N. (1989) Modulation of the voltage-dependent sodium channel by agents affecting G-proteins: a study in Xenopus oocytes injected with brain RNA. Brain Res. 496: 197-203.

Cohen-Armon, M., Sokolovsky, M. (1991) Depolarization-induced changes in the muscarinic receptor in rat brain and heart are mediated by pertussis-toxin-sensitive G-proteins J. Biol. Chem. 266: 2595-2605

Cohen-Armon, M., Sokolovsky, M. (1991) Inhibition of pertussis-toxin catalyzed ADP-ribosylation of G-proteins by membrane depolarization in rat brain synaptoneurosomes Neurosci. Letters 126: 87-90

Cohen-Armon, M., Sokolovsky, M. (1993) Evidence for involvement of the voltage-dependent Na-channel gating in depolarization-induced activation of G-proteins J. Biol. Chem. 268: 9824-9838

Cohen-Armon, M., Hammel, I., Anis, Y., Homburg, S. and Dekel, N. (1996) Evidence for endogenous ADP-ribosylation of GTP-binding proteins in neuronal cell nucleus: Possible induction by membrane depolarization. J. Biol. Chem. 271: 26200-26208

Anis, Y., Nurnberg, B., Visochek L., Reiss, N., Naor, Z. and Cohen-Armon, M. (1999) Activation of Go-proteins by membrane depolarization traced by in-situ photoaffinity labeling of Gαo-proteins with [α32P]GTP-azidoanilide. J. Biol. Chem. 274: 7431-7440.

Chapman, J., Cohen-Armon, M., Shoenfeld, Y., and Korczyn, A. D.(1999) Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes. LUPUS 8:127-133.

Homburg, S., Visochek, L., Moran, N., Dantzer, F., Priel, E., Asculai, E., Schwartz, D., Rotter, V., Dekel, N., Cohen-Armon, M. 2000. A fast signal-induced activation of poly(ADP-ribose) polymerase: A novel downstream target of phospholipase C. J. Cell Biol. 150 (2) :293-307.
Editorial: ‘Depolarization activates PARP’ J Cell Biol. 150 (2):2.

Cohen-Armon M., Visochek L., Katzoff A., Levitan D., Susswein A.J., Klein R.,Valbrun M., and Schwartz J.H. 2004. Long-term memory requires polyADP- ribosylation. Science 304: 1820-1823.
Editorial: ‘DNA damage and Long-Term Memory‘, Science 304:1715.

Visochek L., Steingart R., Vulih R.A., Klein R., Priel E., Gozes I., and Cohen-Armon M. 2005. PolyADP-ribosylation is involved in neurotrophic activity J Neurosci. 25:7420-7428.
Editorial: PARP-1 activation and neurotrophins J Neurosci. 25: 1.
Maymon BB, Cohen-Armon M, Yavetz H, Yogev L, Lifschitz-Mercer B, Kleiman SE,Botchan A, Hauser R, Paz G.2006. Role of poly(ADP-ribosyl)ation during human spermatogenesis.Fertil Steril. 86:1402-1407.

Cohen-Armon M., Visochek L., Rozensal D., Kalal A., Klein R., Bendetz- Netzer S., Yao Z., and Seger R. 2007. DNA-independent PARP-1 activation by phosphorylated ERK2 increases Elk1 activity: A link to histone acetylation. Mol. Cell 25: 297-308

Cohen-Armon M. 2007. PARP-1 activation in the ERK signaling pathway . Trend Pharmacol. Sci. 28: 556-560
Goldberg S., Visochek L, Giladi E.,Gozes I.,and Cohen-Armon M. 2009. PolyADP-ribosylation is required for long-term memory formation in mammals. J. Neurochem. 111:72-9.

Inbar-Rozensal D., Visochek L., Castel D., Castiel A., Izraeli S., Dantzer F. and Cohen-Armon M. 2009. A selective eradication of human nonhereditary breast cancer cells by phenanthridine-derived polyADP-ribose polymerase inhibitors. Breast Cancer Res. 11(6):R78.
Editorial: Kristine M Frizzell, W Lee Kraus. 2009 PARP inhibitors and the treatment of breast cancer: beyond BRCA1/2? Breast Cancer Research 11:111
Press release: http://www.eurekalert.org/pub_releases/2009-11/bc-sot110309.php

Castiel A., Visochek L., Mittelman L., Dantzer F., Izraeli S., and Cohen-Armon M. 2011. A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells BMC Cancer 11:412

Geistrikh I., Visochek L., Klein R., Miller L., Mittelman L., Shainberg A. and Cohen-Armon M. 2011. Ca2+ induced PARP-1 activation and ANF expression are coupled events in cardiomyocytes Biochem J. 438: 337–347

Inbar D., Cohen-Armon M., Neumann D. 2012. Erythropoietin-driven signaling and cell migration mediated by polyADP-ribosylation Br. J. Canc. 107(8):1317-1326

Cohen-Armon (2012) PARP1 activation is required for long-term memory. In: Long-Term
Memory: Mechanisms, Types and Disorders Nova Science Publishers, Inc. ISBN 978-1-61942-699-3

Castiel A., Visochek L., Mittelman L., Zilberstein Y., Dantzer F., Izraeli S., Cohen-Armon M. 2013, Confocal imaging of live cancer cells harboring extra-centrosomes in mitosis, J Vis Exp. 78, doi: 10.3791/50568

A PARP1-ERK2 synergism is required for the induction of synaptic plasticity By: Cohen-Armon, M. 2015 Conference: 40th Congress of the FEBS - The Biochemical Basis of Life Berlin, GERMANY Date: JUL 04-09, 2015 FEBS JOURNAL Volume: 282 Special Issue: SI Pages: 70-71

Biro A., Vaknin H., Cohen-Armon M.,  et al., 2016 The effect of polyADP-ribose polymerase inhibition on Aminoglycoside-induced acute tubular necrosis in rats. Clin. Neph. DOI:10.15414/CN108697 

Visochek L, Kalal A, GrigoryanG, Milshtein-Parush H, Gazit N, Slutsky I, Yecheskel A., Shainberg A,Castiel A, Seger R., Langelier M.F., Dantzer F,  Pascal J., Segal M, Cohen-Armon M. 2016. A PARP1-ERK2 synergism is required for the induction of LTP. Sci.Rep 6, 24950; doi: 10.1038/srep24950.

Elad Lax, Alexander Friedman, Renaud Massart, Royi Barnea, Lital Abraham, Leonid Visochek, Matthew Suderman, Malka Cohen-Armon, Moshe Szyf and Gal Yadid, 2016. PARP-1 is Required for Retrieval of Cocaine-Associated Memory by Binding to the Promoter of a Novel Gene Encoding a Putative Transposase Inhibitor. Mol Psychiatry  2016 Sep 6. doi: 10.1038/mp.2016.119.

Cohen-Armon. 2016 PARP1-Erk2 synergism is required for stimulation-induced expression of Immediate Early Genes  Gene & Translational Bioinformatics 2016, 2: e1367. doi: 10.14800/gtb.1367  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5110042/.

Leonid Visochek, Dikla Atias, Asher Castiel, Leonid Mittelman, Michael Elkin,Talia Golan, Shai Izraeli, Tamar Peretz, Malka Cohen-Armon 2017 Exclusive destruction of mitotic spindles in human cancer cells Oncotarget 8(13), 20813-20824. fromhttp://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=view&path%5B%5D=15343 

2012017 Feb 15. doi: 10.18632/oncotarget.15343

 Visochek L, Cohen-Armon M. 2018 PARP1-Erk synergism in proliferating cells.  Oncotarget 9(49),29140-29145

Cohen-Armon M., Yeheskel A., Pascal J.M. A signal-induced PARP1-Erk synergism  mediates IEG expression Nature- Signal Transduction and Targeted Therapy 2019,4,1-8  

     A PARP1-ERK2 synergism is required for the induction of LTP

Short title:

         A PARP-ERK synergism for learning 

L. Visochek2, G. Grigoryan10§, A. Kalal 1,2,  H. Milshtein-Parush1,3, N. Gazit1,3, I. Slutsky1,3, A. Yeheskel4, A.  Shainberg5, A. Castiel6,  R. Seger8, M.F. Langelier9, F. Dantzer7, J.M. Pascal9, M. Segal10, M. Cohen-Armon1

https://med.tau.ac.il/sites/medicine.tau.ac.il/files/media_server/medicine/SackerMedResearchReport_January2016.pdf