Prof. Malka Cohen-Armon
Researcher & Scientist at the Sackler School of Medicine, Physiology & Pharmacology, and Sagol School of Neuroscience, Tel Aviv University
https://www.oncotarget.com/videos/interview/interview-with-prof-malka-cohen-armon/
Introduction
The general focus of our research is on signal transduction mechanisms causing chromatin modification that control gene expression. We discovered a new molecular mechanism mediating immediate eally gene expression . This mechanism underlies a variety of processes in long-term memory consolidation, in proliferation, growth, and development in normal and malignant cells and in pathological modification and death of cardiomyocytes. In view of my interest in excitability, some of the work in our lab uses voltage stimulation of primary brain cortical cultured cells. This kind of stimulation revealed molecular processes induced by stimulations inducing synaptic activity. These results elucidated the role of chromatin modifications is synaptic plasticity and long-term memory formation during learning which was confirmed in-vivo in mice and the molusk Aplysia. (Cohen-Armon et al., Science 2004; Visochek et al., J Neurosci., 2005; Cohen-Armon et al., Mol Cell, 2007; Goldberg et al., J Neurochem, 2009; Visochek et al., Sci. Rep., 2016). These findings also led to the discovery of PARP1 implication in addiction and PTSD (post-traumatic stress disorders). A project was partly supported by NIH grant 1R21DA027776 in which we disclosed the role of PARP1 inhibitors in preventing addiction (US patent granted 2014).
The accidental finding that the phenanthrene derivative PJ34 designed for protecting from cell death imposed by stress conditions, exclusively eradicates human cancer cells by targeting exclusive mechanisms crucial for normal mitosis in human cancer cells. The activity of this molecule disclosed a new mechanism generally causing cell death during mitosis in human cancer cells. Its activity is shared by other phenanthrene derivatives which less efficiently eradicated cancer cells. Despite the fact that PJ34 also acts as a PARP inhibitor, PARP1 inhibition was not required for the Mitotic Catastrophe Cell death imposed by this phenanthrene derivatives, and its activity is not shared by other PARP inhibitors (Inbar-Rozensal et al., Breast Canc. Res., 2009; Castiel et al., BMC Cancer, 2011; Castiel et al., JoVE, 2013, Oncotarget 2017, 2019). In this cell death mechanism, the more rapidly cancer cells proliferate the more efficiently they are eradicated by PJ34, while normal cells both quiescent and proliferating normal cells are not affected by this molecule. On 2019 the efficiency of PJ34 has been denstrated in mouse xenografts developing human pancreatic cancer tumors. This most efficient eradication of human pancreatic cancer cells in tumors which did not impaire the wellfare of the mice including weight gain led us to the to examine the therapeutic potential of PJ34 for targeted cancer therapy, suitable for aggressive cancers that are resistant to current therapies. The recently summarized reports of many other groups https://doi.org/10.3390/cancers12061628 encouraged this idea. Based on our patents (EU and US patents granted on 2013, 2014 and 2016) we are trying to develop PJ34 for clinical trials.
BIOGRAPHICAL SKETCH
NAME: Cohen-Armon Malka
POSITION TITLE: Professor
EDUCATION/TRAINING
INSTITUTION AND LOCATION
DEGREE
Completion Date
FIELD OF STUDY
Technion, Haifa B.Sc. 1972 Chemistry (Suma Cum Laude)
Technion, Haifa D.Sc. 1980 Biophysics and Electrophysiology, Supervisor: Prof Yoram Palti
Tel-Aviv University, Faculty of Life Science
Post-Doc training 1983-1989 Neurobiochemistry
Positions and Employment
Years Position, Place
1973-1978 Instructor, Biophysics and Electrophysiology, Medical School, Technion
1990-1995 Assistant Professor-Research, Physiology and Pharmacology, Sackler School of Medicine, Tel-Aviv
1996 – 2007
2001 Visiting Researcher, HFSP fellow, in Columbia University, Center for Neurobiology and Behavior, NY, USA,
2008-present
Associate Professor -Research, Physiology and Pharmacology, Cardiac research institute, Sackler
School of Medicine, Tel Aviv University
Lecturer in the Program for Advanced Studies, Sackler School of Medicine, on Signal-Transduction
Mechanisms.
Academic Editor: Plos One; Am. J. Alzheimer's Disease & Other Dementias, Cells
Contribution to Science
(1) Discovered voltage dependence of G-protein coupled receptors' affinity for agonists
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-
dependentsodium channel by agents affecting G-proteins: a study in Xenopusoocytes
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
ADPribosylation 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
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.
Dekel N, Visochek L., Anis Y., Cohen-Armon M. (2003) Stimulation induced
modification in Go-proteins in giant fused synaptoneurosomes J. Mol Neurosci. 20,
73-80
Editorial: Voltage sparks the GPCR by: Peter Stanfield. Nature Cell Biol.8(12),1323, 2006
(2) Identified mechanism underlying the anti-phospholipid induced central disorders
Chapman, J., Cohen-Armon, M., Shoenfeld, Y., and Korczyn, A. D.(1999)
Antiphospholipid antibodies permeabilize and depolarize brain synaptoneurosomes.
LUPUS 8:127-133.
(3) Identified crucial role of chromatin modification in long-term memory formation
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.
Editorials:‘DNA damage and Long-Term Memory‘, Science 304:1715, 2004
Neuronal plasticity: PARP1 allows lasting memories Nature Rev. Neurosci. 5, 597 2004
https://doi.org/10.1038/nrn1482
Press release: http://www.alzforum.org/news/research news/learning-molluscs
polyADP-ribosylation and-memory
PARP1 activation mediates the expression of immediate early genes implicated in longterm
memory. By M. Cohen-Armon FEBS J. 275, 92, Oral Presentation 33rd FEBS conference Athens, 2008
Goldberg S., Visochek L, Giladi E.,Gozes I.,and Cohen-Armon M. 2009. PolyADPribosylation
is required for long-term memory formation in mammals. J. Neurochem.111:72-9.
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
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 (Nature) 6, 24950; doi: 10.1038/srep24950.
Press release: http://www.hayadan.org.il/mechanism-for-the-creation-of-long term-
memory-0806166 Identified the effect of polyADP-ribosylation on addiction:
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. doi: 10.1038/mp.2016.119.
Patent: "Treatment of addiction" application 13/761,761, granted Oct 2014 US 08889707B1
(4) Identified the role of chromatin remodeling by polyADP-ribosylation in signal transduction
mechanisms
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
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 ofpoly(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.
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
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 JUL 2015 FEBS J. Volume: 282 Special Issue: SI Pages: 70-71
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
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
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/PMC5110
042/.
Malka Cohen-Armon, Adva Yeheskel, John M.Pascal. 2019. A signal-induced
PARP1-Erk synergism mediates IEG expression. Review submitted to Signal
Transduction and Targeted Therapy (Nature) 8;4.doi.org/10.1038/s41392-019-0042-0
Cohen-Armon M. A Long-Lasting PARP1-Activation Mediates Signal-Induced Gene Expression. Cells. 2022; 11(9):1576. https://doi.org/10.3390/cells11091576
(5) Identified mechanism causing exclusive eradication of human
cancer cells during mitosis
Inbar-Rozensal D., Visochek L., Castel D., Castiel A., Izraeli S., Dantzer F. CohenArmon
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 declustering
agent exclusively eradicating human cancer cells BMC Cancer 11:412
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
Castiel A., Visochek L., Mittelman L., Zilberstein Y., Dantzer F., Izraeli S., Cohen-
Armon M. 2013, Confocal imaging of live cancer cells harboring extracentrosomes
in mitosis, J Vis Exp. 78, doi: 10.3791/50568
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.
Press release: https://www.tau.ac.il/research/exclusive-destruction
https://www.sciencedaily.com/releases/2017/03/170327102352.htm
Visochek L, Cohen-Armon M. 2018 PARP1-Erk synergism in proliferating cells.
Oncotarget 9(49),29140-29145
Leonid Visochek, Dikla Atias, Itay Spektor, Asher Castiel, Talia Golan and
Malka Cohen-Armon 2019 The phenanthrene derivative PJ34 exclusively
eradicates human pancreatic cancer cells in xenografts Oncotarget
10:6269-6282
Press release: http://www.oncotarget.com/news/pr/the-phenanthrene-derivativepj34-
exclusively-eradicates-human-pancreatic-cancer-cells-in-xenografts/
Malka Cohen-Armon 2020 The modified phenanthridine PJ34 unveils an
exclusive cell death mechanism in human cancer cells
Cancers (Basel). 2020 Jun 19;12(6):1628. doi: 10.3390/cancers12061628.
The modified phenanthridine PJ34, 2020, https://encyclopedia.pub/2666
Malka Cohen-Armon Exclusive modifications of NuMA in malignant epithelial cells:
A potential therapeutic mechanism 2022
Drug Discovery Today, online pre-proof version
https://doi.org/10.1016/j.drudis.2022.02.002
Patents: Cancer therapy. US 8,729,080B2 granted 2014, US 9,486,449B2 granted
2016. Wo2009/047752 granted 2013, EP2207548B1.
Treatment of Addiction granted 2014 US 8,889,707 B2
Phenancure Ltd. foundation 2017.
Heading 2
Achievements
Voltage-dependent activation of Go-proteins mediates the affinity modulation of G-protein-coupled muscarinic receptors
https://doi.org/10.1073/pnas.82.10.3524
https://doi.org/10.1016/S0021-9258(18)52287-0
Are Voltage Sensors Really Embedded in Muscarinic Receptors? 2023 HTTP:// doi.org/10.3390/ijms24087538
PARP1 activity is required for long-term memory acquisition
DOI: 10.1126/science.1096775
https://rdcu.be/cDr1E
Wikipedia: Hist1H1A
HFSP Fellow in Columbia University, Center for Neurobiology and Behavior
Cohen-Armon et al., Science, 2004,304:1820-1823
Science Signaling Editors choice DOI: 10.1126/stke.2382004TW223
Sci Rep. (Nature) 2016, 6: 24950
PARP1 activity is required for long-term memory acquisition
DOI: 10.1126/science.1096775
A link to my talk at the CSHL PARP meeting on Dec. 2020. PARP1- Erk2 synergism implicates PARP1 in long-term memory acquisition and loss
https://www.dropbox.com/s/74f6a016uaj6c6u/Cohen-Armon%20copy.mp4?dl=0
US Patent: Treatment of addiction 8,889,707B2, granted 2014
A PARP1-Erk synergism: Signal-induced PARP1 binding to phosphorylated Erk activates PARP1, facilitates and prolongs Erk activity in the chromatin, and mediates immediate-early gene expression
J. Cell Biol. 150 (2):293-307,2000 Sig. Trans. & Targ. Ther. (Nature) 8;4,2019
Trend Pharmacol. Sci. 28: 556-560,2007
Cohen-Armon M. A Long-Lasting PARP1-Activation Mediates Signal-Induced Gene Expression. Cells. 2022; 11(9):1576.
PARP1 acts as an anchoring protein of phosphorylated Erk in the nucleus. Docking of phosphorylated Erk2 in specific sites in PARP1 activated PARP1. This is prevented in PARP-bound to DNA breaks due to the occlusion of the Erk docking sites on PARP1. Their occlusion down-regulates Erk-induced gene expression in aging and degenerative diseases.
Binding of PARP1 to phosphorylated Erk (a) vs. PARP1 binding to DNA (b)
Mol. Cell 25: 297-308,2007
Sci Rep. (Nature) 6: 24950, 2016
The modified phenanthridine PJ34 exclusively eradicates a variety of human cancer cells in cell cultures and xenografts without impairing healthy cells. In development for clinical trials
Patent: Cancer therapy. US 8,729,080B2 granted 2014, US 9,486,449B2 granted2016. Wo2009/047752 granted 2013, EP2207548B1.
An Unveiled Cell-Death Mechanism Exclusive to Human Cancer Cells
In: Precision Oncology: Translating Discovery to the Clinic
June 21-24, 2021 | 9:00AM EDT | 1:00PM UTC | 3:00PM CEST*
https://virtual.keystonesymposia.org/ks/live/817/page/8222?entryId=24874
In: Discovery Ontarget meeting 2021
https://discoveryontarget.us2.pathable.com/meetings/virtual/enodukgBrcTD7ZKCB
Exclusive modifications of NuMA in malignant epithelial cells: A potential therapeutic mechanism Drug Discovery Today Volume 27, Issue 5, May 2022, Pages 1205-1209
https://doi.org/10.1016/j.drudis.2022.02.002
AACR Annual Meeting 2024, Abs.1642: NuMA exclusive post-translational modification in human cancer epithelial cells is a novel target for cell eradication Cancer res. 2024,84
Guest Editor: https://www.mdpi.com/journal/cells/special_issues/
PARP_Proteins in signal transduction mechanisms and chromatin remodeling
In the Media
2022
Interview for Ashai Japan TV:
2019-2021
https://www.i24news.tv/en/news/technology/1575382997-new-pancreatic-cancer-treatment-by-israeli-researchers-eradicates-disease-in-two-weeks
https://www.sciencedaily.com/releases/2019/12/191203102018.htm
https://israelbetweenthelines.com/2019/12/05/pancreatic-cancer-treatment-trail-proves-hopeful/
https://www.youtube.com/watch?v=FyQcIjzz3I4
https://www.israel21c.org/scientists-discover-molecule-that-destroys-pancreatic-cancer-cells/
https://www.drugtargetreview.com/people/professor-malca-cohen-armon/
https://www.timesofisrael.com/topic/malka-cohen-armon/
https://nocamels.com/2019/12/israeli-study-molecule-destruction-pancreatic-cancer-cells/
https://www.sciencedaily.com/releases/2019/12/191203102018.htm
https://ecancer.org/en/news/17014-new-treatment-triggers-self-destruction-of-pancreatic-cancer-cells
https://www.wikigenes.org/e/author/e/753242.html
https://interestingengineering.com/researchers-identify-molecule-that-can-kill-cancer-cells
https://israelbetweenthelines.com/2019/12/05/pancreatic-cancer-treatment-trail-proves-hopeful/
https://www.scientificamerican.com/article/unmasking-memory-genes/
https://www.futuretimeline.net/blog/2019/12/6-2.htm
http://www.europereloaded.com/tag/prof-malca-cohen-armon/
https://indianewengland.com/2019/12/researchers-find-new-way-to-treat-pancreatic-cancer/
https://www.sciencealert.com/scientists-discover-a-new-way-to-get-cancer-cells-to-self-destruct
https://www.aftau.org/weblog-medicine--health?&storyid4704=2322&ncs4704=3
https://www.goodnewsnetwork.org/molecule-triggers-self-destruction-of-pancreatic-cancer-cells/
https://cftau.ca/new-treatment-triggers-self-destruction-of-pancreatic-cancer-cells/
https://www.jns.org/scientists-discover-molecule-that-destroys-pancreatic-cancer-cells/
https://www.hayadan.org.il/a-molecule-that-causes-self-extinction-of-pancreatic-cancer-cells-0212191
https://www.youtube.com/watch?v=rUOCwNND9wM
Video Interviews with Featured Cover Paper Authors | Oncotarget
Tel Aviv University's Prof. Malka Cohen-Armon talks about her Publication in the Open-access Bio-medical Journal Oncotarget
Correspondence to - Malka Cohen-Armon, email: marmon@tauex.tau.ac.il
Keywords: PJ34, pancreas cancer, stroma, PANC1 cancer xenografts2020
https://nocamels.com/2020/02/5-medical-advances-israeli-cancer-research-treatment/
https://nocamels.com/2019/12/nocamels-popular-stories-of-2019/
https://gigazine.net/.../20191220-self-destroys.../ in Japan press
2017-2018
Cohen-Armon one of 50 influencial women in 2017 Lady Globs https://www.globes.co.il/news/home.aspx?fid=9610
https://mdanderson.elsevierpure.com/en/publications/exclusive-destruction-of-mitotic-spindles-in-human-cancer-cells
https://sciencebeta.com/phenanthridine-pj34-cancer-mitosis/
https://www.tau.ac.il/news/heb/HEBSum10.pdf
2016
http://www.nrg.co.il/online/13/ART2/785/261.html
http://www.hayadan.org.il/mechanism-for-the-creation-of-long-term-memory-0806166
https://www.aftau.org/weblog-medicine--health?&storyid4704=2495&ncs4704=3
https://www.omicsdi.org/dataset/arrayexpress-repository/E-GEOD-83718
https://www.youtube.com/watch?v=FyQcIjzz3I4
http://www.cancerfactorfiction.com
http://www.cancerfactorfiction.com/kidney-cancer/tt-middle-east-breast-cancer-2010-news/
http://www.eurekalert.org/pub_releases/2009-11/bc-sot110309.php
http://www.breakingchristiannews.com/articles/display_art.html?ID=7301
http://www.google.com/search?hl=en&q=aljazeera+english++cohen-armon&aq=f&oq=&aqi=
http://www.google.com/search?hl=en&source=hp&q=al+hurra+cohen-armon&aq=f&oq=&aqi=
2008
Amir levin, Scientific American 2008, Unmasking memory genes19, 48-52
2005
https://www.tau.ac.il/news/heb/HEBSpr05.pdf
https://www.israel21c.org/israeli-research-provides-insight-into-formation-of-lasting-memory/
https://www.medscimonit.com/abstract/index/idArt/15060/act/2
https://www.ynet.co.il/articles/0,7340,L-2970307,00.html
https://www.ynet.co.il/articles/0,7340,L-2970307,00.htm
2004
http://www.nature.com/nrn/journal/v5/n8/full/nrn1482.html
http://www.israel21c.org/health/israeli-research-provides-insight-into-formation-of-lasting-memory/
http://www.alzforum.org/news/research-news/learning-molluscs-polyadp-ribosylation-and-memory
http://www.ynet.co.il/articles/0,7340,L-2970307,00.html
http://www.ynet.co.il/articles/1,7340,L-2945990,00.html
Israeli research provides insight into formation of lasting memory
By ISRAEL21c Staff MAY 4, 2005, 11:00 PM
Tel Aviv University biochemist Dr. Malka Cohen-Armon: Activation PARP1 of the protein is essential to the expression of genes that govern the formation of long-term memory.When we experience a friendly encounter, a new taste or a mental leap, how is it that sometimes these events are imprinted on our minds forever, while other daily occurrences fade into nothingness? The riddle of long-term memory formation has come one step closer to being solved due to a discovery in Israel by Tel Aviv University biochemist Dr. Malka Cohen-Armon of the Sackler Faculty of Medicine
Cohen Armon, in collaboration with scientists at Bar-Ilan University and Columbia University in the US, found that a protein called PARP1, present in the nucleus of cells in animals and plants, is rapidly activated in brain cells in response to external stimulation and allows the formation of lasting memories.
PARP1 itself is not a new discovery; for 40 years, scientists have known that activation of this protein is an early emergency response of cells to stress conditions that can damage the genetic information stored in DNA. These stress conditions include cell aging, injury, inflammation or exposure to radiation. Activation of PARP1 rapidly releases the proteins surrounding the DNA molecule, enabling access to the damaged sites and making it possible for repairs to be made.
Cohen-Armon and her partners discovered a second function of PARP1, unrelated to stress conditions. They showed that activation of the protein is essential to the expression of genes that govern the formation of long-term memory.
“Short-term memory and long-term memory involve different processes,” explains Cohen-Armon. “With short-term memory, no gene transcription is required. Long-term memory formation, however, entails the expression of specific genes.”
PARP1 activation enables these genes to go into action.
“Picture the shutter of a camera,” says Cohen-Armon. “The shutter protects the film in the camera, except that in our case that film is the DNA molecule in a cell’s nucleus, and the shutter is made up of proteins surrounding the DNA. Ordinarily, PARP1 activation opens that shutter to allow repair procedures to breaks in the DNA. We found that this same shutter mechanism opens access to DNA during the learning process, enabling the DNA transcription specific to long-term memorization to occur.”
The researchers tested their theory on the sea slug, Aplysia californica, whose primitive nervous system has been used for three decades as a model for basic functioning of the brain. In training the slug to ignore inedible food, the researchers noted that PARP1 was activated in its nervous system, and that this activation was essential for the slug?s ability to remember this learning task over the long term. Moreover, long-term memory was completely prevented by inhibiting PARP1 activity.
The findings, which were published in Science, highlight a novel mechanism in the pattern of memory formation that may have implications for treating diseases such as Alzheimer?s and Parkinson’s, mental illness, and other conditions that involve memory or concentration impairment.
(Originally appeared in Tel Aviv University News)
Medical News
Israeli Researchers Discover New Agent to Target Cancer Cells
ON APR 21, 2015
Researchers at Tel Aviv University (TAU) have identified a new, highly selective targeted therapy that has the potential to effectively treat breast cancer and a wide range of other solid cancers in humans. The research, supported by a grant from the Israel Cancer Research Fund (ICRF), “is based on a small molecule called PJ-34 that is soluble in water and permeates the cell membrane,” explains lead investigator Prof. Malka Cohen-Armon, of TAU’s Sackler School of Medicine. “This molecule exclusively eradicates a variety of cancer cells without harming normal tissues.” Moreover, the more aggressively are cancer cells proliferating the more efficiently they are eradicated by PJ-34".
PJ-34 is a member of a family of drugs that inhibit poly ADP ribose polymerase 1 (PARP1), a protein involved in repairing damaged DNA. Originally developed more than 10 years ago to preserve nerve cells stressed by a stroke or inflammation, the drugs were found inappropriate for their intended use and were released solely for research purposes. Cohen-Armon and her team began studying how the compound acts within the nucleus of cells in hope of discovering an application for DNA repair.
When PJ-34 was injected into female mice transplanted with the incurable triple negative breast-cancer, the investigators discovered that PJ-34 stopped tumor growth and prevented the development of new tumors. In tissue cultures, PJ-34 prevented cell division and eradicated cancerous cells, while normal cells continued to proliferate (e.g., increasing in number as a result of cell division) .
“We found that PJ-34 and other similar molecules 'turn on' a mechanism specific to human solid cancer cells that causes them to die during cell division without harming normal tissue,” explains Cohen-Armon. “The more rapidly the cancer cells are proliferating the more efficiently they are eradicated by PJ-34” says Cohen-Armon, who believes she and her colleagues have found “an Achilles heel of human solid cancer cell.”
“As soon as you can target cancerous cells without killing healthy ones you can produce efficient medications that would cause a lot less suffering to the patient,” she explained in a recent newspaper interview. “We can even give a much more aggressive treatment without worrying about harming healthy tissues.” Some 233,000 women and 2,400 men will be newly diagnosed with breast cancer in the United States in 2014 and more than 40,000 people will die of the disease, according to the American Cancer Society.
In ongoing research supported by ICRF, Cohen-Armon and her team are working to decipher the molecular mechanisms responsible for the anti-cancer effects of PJ-34. “If we can understand the molecular mechanism and identify the targets of PJ-34, it will open a new mode of therapy for a variety of cancer types", she explains. “We have tested PJ-34 in tissue cultures of aggressive human cancers derived from patients' tumors, including pancreas and non-small lung cancers, glioblastoma, ovary and colon cancers. The encouraging results urge us to develop PJ-34 and its derivatives for cancer therapy without side effects.”
ICRF is a nationwide charitable organization founded in 1975 by a group of American and Canadian researchers, oncologists, and lay people. It is the largest U.S.-based charity solely devoted to supporting cancer research in Israel and receives its total income from private donations.
New Treatment Triggers Self-Destruction of Pancreatic Cancer Cells
Monday, December 02, 2019 9:00:00 AM
Research conducted on human pancreatic tumors transplanted in mice reveals promising results, TAU researchers say
Pancreatic cancer is resistant to all current treatments. Patients have extremely poor chances of surviving for five years after being diagnosed.
A new Tel Aviv University study finds that a small molecule has the ability to induce the self-destruction of pancreatic cancer cells. The research was conducted with xenografts — transplantations of human pancreatic cancer into immunocompromised mice. The treatment reduced the number of cancer cells by 90% in the developed tumors a month after being administered.
The research holds great potential for the development of a new effective therapy to treat this aggressive cancer in humans.
The study was led by Prof. Malca Cohen-Armon and her team at TAU's Sackler Faculty of Medicine, in collaboration with Dr. Talia Golan's team at the Cancer Research Center at Sheba Medical Center. It was published in the journal Oncotarget on October 22.
"In research published in 2017, we discovered a mechanism that causes the self-destruction of human cancer cells during their duplication (mitosis) without affecting normal cells," explains Prof. Cohen-Armon. "We have now harnessed this information to efficiently eradicate human pancreatic cancer cells in xenografts. The current results were obtained using a small molecule that evokes this self-destruction mechanism in a variety of human cancer cells.
"The mice were treated with a molecule called PJ34, which is permeable in the cell membrane but affects human cancer cells exclusively. This molecule causes an anomaly during the duplication of human cancer cells, provoking their rapid cell death. Thus, cell multiplication itself resulted in cell death in the treated cancer cells."
A month after being injected with PJ34 daily for 14 days, the pancreatic cancer cells in the tumors of the treated mice experienced a relative drop of 90%. In one mouse, the tumor completely disappeared.
"It is important to note that no adverse effects were observed, and there were no changes in the weight gain of the mice, nor in their behavior," says Prof. Cohen-Armon.
This mechanism acts efficiently in other types of cancer resistant to current therapies. The molecule PJ34 is being tested in pre-clinical trials according to FDA regulations before clinical trials begin.
The research was funded through contributions to American Friends of Tel Aviv University.
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