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La nostra ricerca sulla rigenerazione cardiaca è stata pubblicata su Nature Cell Biology!

The murine neonatal heart can regenerate after injury through cardiomyocyte (CM) proliferation, although this capacity markedly diminishes after the first week of life. Neuregulin-1 ( NRG1) administration has been proposed as a strategy to promote cardiac regeneration. Here, using loss- and gain-of-function genetic tools, we explore the role of the NRG1 co-receptor ERBB2 in cardiac regeneration. NRG1-induced CM proliferation diminished one week after birth owing to a reduction in ERBB2 expression. CM-specific Erbb2 knockout revealed that ERBB2 is required for CM proliferation at embryonic/neonatal stages. Induction of a constitutively active ERBB2 (ca ERBB2) in neonatal, juvenile and adult CMs resulted in cardiomegaly, characterized by extensive CM hypertrophy, dedifferentiation and proliferation, differentially mediated by ERK, AKT and GSK3β/ β-catenin signalling pathways. Transient induction of ca ERBB2 following myocardial infarction triggered CM dedifferentiation and proliferation followed by redifferentiation and regeneration. Thus, ERBB2 is both necessary for CM proliferation and sufficient to reactivate postnatal CM proliferative and regenerative potentials.

Vai all’articolo originale (in inglese): Gabriele D’Uva, Alla Aharonov, Mattia Lauriola, David Kain, Yfat Yahalom-Ronen, Silvia Carvalho, Karen Weisinger, Elad Bassat, Dana Rajchman, Oren Yifa, Marina Lysenko, Tal Konfino, Julius Hegesh, Ori Brenner, Michal Neeman, Yosef Yarden, Jonathan Leor, Rachel Sarig, Richard P Harvey and Eldad Tzahor. ERBB2 triggers mammalian heart regeneration by promoting cardiomyocyte dedifferentiation and proliferation. Nature Cell Biology, 2015

Scientific recognitions

Science – News: New hope for heart attack sufferers?

NATURE – News and Views: Regenerative biology: Neuregulin 1 makes heart muscle

NATURE REVIEWS DRUG DISCOVERY – Research Highlight: Heart disease – Stimulating cardiomyocyte regeneration after heart failure

NABR: The Essential Need for Animals in Medical Research

MEDIA COVERAGE

06.04.2015 – The Guardian: Heart muscle cells regrown in medical research breakthrough

06.04.2015 – The Sydney Morning Herald: Australian researchers help find way to regrow heart muscle

07.04.2015 – RT: Scientists discover revolutionary method to regrow heart muscles

07.04.2015 – AM: Helping the heart repair itself after a cardiac arrest: researchers say they’ve worked out how

07.04.2015 – Financial Express: The Turbo-charging hormone can repair ‘broken’ heart

07.04.2015 – El Comercio: Logran regenerar músculos del corazón al estimular una hormona

07.04.2015 – SKY NEWS: Breakthrough Sees Heart Muscle Cells Regrown

07.04.2015 – SBS: Scientific breakthrough could give new hope to heart-attack patients

07.04.2015 – The Jewish Press: Israeli-Australian Researchers Discover How to Regrow Heart Muscle

07.04.2015 – Business Magazin: STUDIU: Cercetătorii au reuşit să stimuleze regenerarea celulelor muşchiului cardiac

07.04.2015 – iarul de Iasi: Cercetătorii au reuşit să stimuleze regenerarea celulelor muşchiului cardiac

07.04.2015 – ZeeNews: Scientists regenerate cardiac muscles through hormone stimulation

07.04.2015 – Medical Xpress: Research effort leads to mammalian heart tissue regeneration

07.04.2015 – Kurier: Durchbruch: Forscher lassen Herzmuskelzellen wachsen

08.04.2015 – SBS World NEWS: Researchers Trigger Heart Regeneration After Heart Attack (TV news)

08.04.2015 – The Times of Israel: Medical leap as Israeli researchers regrow heart cells

08.04.2015 – smarTherapy: Consiguen regenerar los músculos del corazón mediante estimulación hormonal

08.04.2015 – Scimondo: Aktivierung eines Hormon-Signalweges hilft Mäuseherzen nach einem Herzinfarkt auf die Sprünge

08.04.2015 – Beyond the Dish: Dead Heart Muscle Regrown in Rodents

08.04.2015 – Phys.org: Research finds turbo-charging hormone can regrow the heart

08.04.2015 – Newsmax: Hormone Found to Regenerate Heart Muscle

09.04.2015 – Medical Daily: Heart Attack Patients May Regrow Cardiac Cells By 2020 Thanks To Breakthrough Discovery

09.04.2015 – The Australian: Bashing corporate Australia has reunited the faceless man with his Green frenemies

10.04.2015 – SILICONWADI: Ricercatori israeliani fanno ricrescere le cellule del cuore

10.04.2015 – Italiasalute.it: Nuova tecnica per curare il cuore infartuato

10.04.2015 – Tiscali: Cuore infartuato, scoperto il meccanismo che avvia la formazione di nuove cellule

10.04.2015 – Ansa: Scoperta la chiave per riparare il cuore infartuato

10.04.2015 – MeteoWeb.eu: Salute: scoperta la chiave per riparare il cuore infartuato

10.04.2015 – Bionn: 拯救心脏 拒绝梗死！ – 大健康产业专区- 生物谷

11.04.2015 – Giornale di Sicilia: Cuore colpito da infarto, scoperta la chiave per ripararlo

12.04.2015 – Il Quotidiano di Puglia: Con questo gene riparerò il cuore

12.04.2015 – NurseTimes: Scoperta la chiave per riparare il tessuto cardiaco infartuato

13.04.2015 – Il Sole 24 Ore: Cuore, identificato gene capace di “ripararlo”

13.04.2015 – HealthCanal: Heart Cells Regenerated in Mice

13.04.2015 – IBA: הלב את מחדשים

13.04.2015 – Radio Jai: Científicos de Israel regeneran células del corazón de ratones

13.04.2015 – EnlaceJudío: Científicos israelíes regeneran células cardíacas

13.04.2015 – israel21c: Weizmann Institute scientists regenerate heart cells in mice

13.04.2015 – IsraCast: Medical Breakthrough – Israeli Scientists Find Way to Regrow Heart Muscle Cells

13.04.2015 – Science Daily: Heart cells regenerated in mice

13.04.2015 – Popular Science: Scoperta la chiave per riparare il cuore infartuato

13.04.2015 – Science Codex: Heart cells regenerated in mice in NGR1 study

13.04.2015 – Science 2.0: Heart Cells Regenerated By Going Backward To Make Progress

13.04.2015 – ScienceBlogs – The Weizmann Wave: Guest post: Dr. Gabriele D’Uva: How to Grow New Heart Cells

13.04.2015 – Il Resto del Carlino: Nuove cellule grazie alla ricerca. Così si ripara il cuore infartuato

14.04.2015 – The Jerusalem Post: Weizmann Institute researchers regenerate heart cells in mice

14.04.2015 – Farmacia.it: Lotta all’infarto: il cuore potrà essere riparato

14.04.2015 – ANI News: Regeneration of heart cells possible in mice

14.04.2015 – Business Standard: Regeneration of heart cells possible in mice

14.04.2015 – New Kerala: Regeneration of heart cells possible in mice

14.04.2015 – Corriere del mezzogiorno: Studio il cuore, sogno l’Italia

14.04.2015 – Israel Hayom: Israeli scientists make revolutionary discovery, regenerate heart cells

14.04.2015 – Genetic Engeneering & Biotechnology News: Old Heart Cells Divide Like New

14.04.2015 – Daily News & Analysis: Scientists regenerate heart cells in mice

14.04.2015 – Cardiovascular Disease News: Study Advances Understanding of Heart Cells’ Regeneration

14.04.2015 – Comité Central Israelita Uruguay: Científicos israelíes regeneran células cardíacas

14.04.2015 – Prahova: Cercetatorii au reusit sa stimuleze regenerarea celulelor muschiului cardiac

14.04.2015 – Iran Daily: Heart cells regenerated in mice

14.04.2015 – Horizon 2020 projects: ERC-funded research sees mouse heart cells renewed

14.04.2015 – Israeli Ministry of Foreign Affairs: Heart cells regenerated in mice

14.04.2015 – MedIndia: Regeneration of Heart Cells Possible in Mice With the Help of Specialized Protein, ERBB2

14.04.2015 – DAILYROUNDS: Successful heart muscle regeneration in mice may soon be seen in humans

14.04.2015 – Jns: Israeli Scientists Regenerate Heart Cells in Revolutionary Discovery

15.04.2015 – The Algemeiner: Israeli Scientists Regenerate Heart Cells in Revolutionary Discovery

15.04.2015 – Nature子刊：ERBB2触发哺乳动物心脏再生是通过促进心肌细胞去分化和增殖

15.04.2015 – Sanità Salento: Un cuore rigenerato per gli infartuati (con intervista radiofonica)

15.04.2015 – Medical Insider: Ученые научились восстанавливать сердечную мышцу

16.04.2015 – Diario del web: Scienziati rigenerano le cellule del cuore

17.04.2015 – Innovations Report: Weizmann Institute Scientists Regenerate Heart Cells in Mice

18.04.2015 – Globus Magazine: RIGENERAZIONE CARDIACA: TROVATA LA CHIAVE PER RIPARARE IL CUORE INFARTUATO

19.04.2015 – Ultime Tecno-scientifiche: COSI’ SI RIPARA IL CUORE INFARTUATO

19.04.2015 – Corriere di Bologna: Gabriele, il ricercatore che ha riacceso il cuore e vuol tornare in Italia

20.04.2015 – Giannella channel: È italiano il medico che ha scoperto come riparare un cuore infranto

20.04.2015 – PolskieRadio: Komórki serca potrafią się zregenerować po zawale

21.04.2015 – multibriefs: Researchers regenerate heart cells in mice

23.04.2015 – UNIBO MAGAZINES: Ecco il gene chiave per riparare il cuore dopo un infarto

23.04.2015 – UNI news24: ERBB2: scoperto il gene che rigenera il cuore dopo un infarto

23.04.2015 – La Repubblica: Trovato un gene per riparare il cuore dopo un infarto

23.04.2015 – RaiNews: Un gene ripara-cuore

23.04.2015 – Rai3 – TGR Emilia Romagna (TV news – min. 15:34)

23.04.2015 – Bologna2000.it: Identificato un gene chiave capace di riparare il cuore danneggiato da un infarto

23.04.2015 – SassuoloOnline: Identificato un gene chiave capace di riparare il cuore danneggiato da un infarto

23.04.2015 – L’Adige: Scoperto gene per riparare il cuore dopo l’infarto

23.04.2015 – Controcampus.it: Gene chiave salva il cuore dopo un infarto, ricerca Unibo

23.04.2015 – Virgilio Notizie: Scoperto un gene per riparare il cuore dopo un infarto

23.04.2015 – TRC: Post infarto, importante scoperta medica

23.04.2015 – AGI: Ricerca Unibo: identificato gene per riparare cuore dopo infarto

23.04.2015 – BolognaToday: Ricerca Unibo: scoperto gene chiave per riparare il cuore dopo un infarto

27.04.2015 – Viversani: Scoperto un gene per riparare il cuore dopo un infarto

27.04.2015 – ResearchItaly: Identified the gene that can repair the heart after a heart attack

27.04.2015 – Biotechin: A “Hearty” discovery – Turbo-charging hormone can regrow the heart

28.04.2015 – Salzburger Nachrichten: Krebs-Wachstumsrezeptor steuert Regeneration von Herzzellen

29.04.2015 – HealthCanal: HEART ATTACK BREAKTHROUGH

02.05.2015 – LiveUniversity: Scoperto gene chiave capace di riparare il cuore danneggiato da un infarto

06.05.2015 – The Australian Jewish News: A heartening collaboration

06.05.2015 – Iton Gadol: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments

06.05.2015 – AJN: Avances. Investigadores israelíes regeneran células del corazón para tratar la enfermedad cardiac

06.05.2015 – NoCamels: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments

06.05.2015 – vetscite.org: Heart cells regenerated in mice

07.05.2015 – Yad be Yad: Investigadores israelíes regeneran células del corazón para tratar enfermedades cardíacas

08.05.2015 – Classic Chaos: Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments

14.05.2015 – VitAssistance: Cuore, identificato gene capace di ripararlo

6.06.2015 – Ruthfully yours: Amazing Israel :Researchers Regenerate Heart Cells In What Could Be A Huge Breakthrough For Heart Disease Treatments

Pubblicato il

Il nostro articolo è su Nature Communications! Siamo felici di aver contribuito a questo ambizioso progetto internazionale sugli ormoni steroidei nello sviluppo del cancro!

Signal transduction by receptor tyrosine kinases (RTKs) and nuclear receptors for steroid hormones is essential for body homeostasis, but the cross-talk between these receptor families is poorly understood. We observed that glucocorticoids inhibit signalling downstream of ​EGFR, an RTK. The underlying mechanism entails suppression of ​EGFR’s positive feedback loops and simultaneous triggering of negative feedback loops that normally restrain ​EGFR. Our studies in mice reveal that the regulation of ​EGFR’s feedback loops by glucocorticoids translates to circadian control of ​EGFR signalling: ​EGFR signals are suppressed by high glucocorticoids during the active phase (night-time in rodents), while ​EGFR signals are enhanced during the resting phase. Consistent with this pattern, treatment of animals bearing ​EGFR-driven tumours with a specific kinase inhibitor was more effective if administered during the resting phase of the day, when glucocorticoids are low. These findings support a circadian clock-based paradigm in cancer therapy.

Vai all’articolo originale (in inglese): Mattia Lauriola, Yehoshua Enuka, Amit Zeisel, Gabriele D’Uva, Lee Roth, Michal Sharon-Sevilla, Moshit Lindzen, Kirti Sharma, Nava Nevo, Morris Feldman, Silvia Carvalho, Hadas Cohen-Dvashi, Merav Kedmi, Nir Ben-Chetrit, Alon Chen, Rossella Solmi, Stefan Wiemann, Fernando Schmitt, Eytan Domany & Yosef Yarden. Diurnal suppression of ​EGFR signalling by glucocorticoids and implications for tumour progression and treatment. Nature Communications, 2015

 

MEDIA COVERAGE

06.10.2014 – Science Daily Tumors might grow faster at nigh

06.10.2014 – NATURE WORLD NEWS: Is Cancer Growth Nocturnal?

06.10.2014 – Softpedia: Cancer Tumors Appear to Grow Faster and Spread More Easily at Night

06.10.2014 – Medical Xpress: Tumors might grow faster at night: Hormone that keeps us alert also suppresses the spread of cancer

06.10.2014 – Senior Journal: Cancer Grows at Night, Maybe That’s When to Attack, New Study Says

07.10.2014 – Daily Mail: Cancerous tumours ‘grow faster at night’ – and drugs to fight the disease might work better during sleep, study finds

07.10.2014 – Counsel&Heal: Cancer Treatment More Efficient During Night Time:Study

07.10.2014 – Science 2.0: Cancer Might Grow Faster At Night

07.10.2014 – The Health Site: Revealed — cancer spreads during nights

07.10.2014 – bhataramedia: Tumor Dapat Tumbuh Lebih Cepat Di Malam Hari

07.10.2014 – Jews News: Israeli study: Tumors might grow more quickly at night

08.10.2014 – The Times of Israel: Tumors may grow faster at night, Israeli study shows

08.10.2014 – Journal de la Science: Les tumeurs grossiraient plus vite la nuit

08.10.2014 – Haaretz: Night time may be the right time to treat cancer, find Israeli scientists

09.10.2014 – Weizmann USA: Why Cancer Drugs May Work Better While You Sleep

09.10.2014 – Nature子刊：夜间癌细胞扩散的更快？

09.10.2014 – TIME: Why Cancer Drugs May Work Better While You Sleep

09-10-2014 – Medisite: CANCER : LES MÉDICAMENTS PLUS EFFICACES LA NUIT

10.10.2014 – TopSante: Cancer : les tumeurs se développent plus vite la nuit

10.10.2014 – Forbes: Cancer May Grow Faster While We Sleep

10.10.2014 – Jerusalem Post Tumors may grow faster at night, say Weizmann scientists

10.10.2014 – Medcenter: Una hormona que nos mantiene alerta también suprime la diseminación del cáncer

16.10.2014 – EACR (European Association for Cancer Research): TUMOURS MIGHT GROW FASTER AT NIGHT

16.10.2014 – Revista Genetica Medica: Ritmos circadianos y tratamiento contra el cáncer

17.10.2014 – University Herald: Hormone Active During Day Supresses Growth of Cancer Cells, Study

20.10.2014 – Stato Quotidiano: Ricercatrice Manfredonia: “tumori crescono più in fretta di notte”

24.10.2014 – Huffington Post: Does Cancer Grow More Aggressively at Night?

Pubblicato il

La nostra ricerca su meccanismi post-trascrizionali in cellule staminali tumorali è stata pubblicata!

Hypoxia has been long-time acknowledged as major cancer-promoting microenvironment. In such an energy-restrictive condition, post-transcriptional mechanisms gain importance over the energy-expensive gene transcription machinery. Here we show that the onset of hypoxia-induced cancer stem cell features requires the beta-catenin-dependent post-transcriptional up-regulation of CA9 and SNAI2 gene expression. In response to hypoxia, beta-catenin moves from the plasma membrane to the cytoplasm where it binds and stabilizes SNAI2 and CA9 mRNAs, in cooperation with the mRNA stabilizing protein HuR. We also provide evidence that the post-transcriptional activity of cytoplasmic beta-catenin operates under normoxia in basal-like/triple-negative breast cancer cells, where the beta-catenin knockdown suppresses the stem cell phenotype in vitro and tumor growth in vivo. In such cells, we unravel the generalized involvement of the beta-catenin-driven machinery in the stabilization of EGF-induced mRNAs, including the cancer stem cell regulator IL6. Our study highlights the crucial role of post-transcriptional mechanisms in the maintenance/acquisition of cancer stem cell features and suggests that the hindrance of cytoplasmic beta-catenin function may represent an unprecedented strategy for targeting breast cancer stem/basal-like cells.

Vai all’articolo originale (in inglese): Gabriele D’Uva*, Sara Bertoni, Mattia Lauriola, Sabrina De Carolis, Annalisa Pacilli, Laura D’Anello, Donatella Santini, Mario Taffurelli, Claudio Ceccarelli, Yosef Yarden, Lorenzo Montanaro, Massimiliano Bonafé, Gianluca Storci. Beta-Catenin/HuR Post-Transcriptional Machinery Governs Cancer Stem Cell Features in Response to Hypoxia. PloS One, 2013 (co-corresponding author)

Pubblicato il

La nostra ricerca su ormoni steroidei e cellule staminali ematopoietiche è stata pubblicata su Leukemia!

The role of corticosterone (Cort), the immune system’s major stress hormone, in the regulation of hematopoietic stem and progenitor cells (HSPCs) and their dynamic bone marrow (BM) microenvironment is currently unknown. We report that corticotropin-releasing factor receptor 1 (CRFR1) mutant mice with chronically low Cort levels showed aberrant HSPC regulation, having higher HSPC numbers and upregulation of the chemokine CXCL12, phenotypes that were restored by Cort supplementation. Expanded stromal progenitors known to support HSPCs were also observed in these low-Cort-containing mice. A similar phenotype was induced in wild-type (WT) mice by Metyrapone, a Cort synthesis inhibitor. Conversely, high Cort exposure induced HSPC apoptosis, reduced long-term BM repopulation and decreased stromal progenitor cell numbers. We documented circadian oscillations of Cort in WT BM but not in CRFR1 mutant mice, leading to diminished circadian BM CXCL12 fluctuations and increased number of circulating HSPCs in these mice. Finally, low Cort induced expansion of stromal progenitors, CXCL12 expression, HSPC proliferation and BM repopulation capacity, involving Notch1 signaling. This was associated with upregulation of the Notch ligand, Jagged1, in BM myeloid cells. Our results suggest that daily physiologic Cort oscillations are critical for balanced HSPC proliferation and function involving Notch1 signaling and their supportive BM microenvironment.

Vai all’articolo originale (in inglese): O Kollet*, Y Vagima*, G D’Uva, K Golan, J Canaani, T Itkin, S Gur-Cohen, A Kalinkovich, G Caglio, C Medaglia, A Ludin, K Lapid, E Shezen, A Neufeld-Cohen, D Varol, A Chen, T Lapidot. Physiologic corticosterone oscillations regulate murine hematopoietic stem/progenitor cell proliferation and CXCL12 expression by bone marrow stromal progenitors. Leukemia, 2013 (* equal contribution)

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