IGM former student seminar – Daisy Sproviero

Martedì 27 FEBBRAIO 2024

Aula “A.Falaschi” IGM LLCS di Pavia

ore 14:30

Daisy Sproviero

Guest Researcher in Genome Instability and Metabolism Reprogramming Lab at IFOM

Parkinson’s disease patients display a DNA damage signature in bloodthat is predictive of disease progression

Sara Tavella CNR DSB Prize

CNR-IGM, Istituto di Genetica Molecolare “Luigi Luca Cavalli Sforza” is proud to announce that Sara Tavella was awarded with the DSB 2023 Scientific Prize for the research topic entitled: “Molecular, cellular, immunological and epidemiological aspects of the #SARS-#CoV2 #infection”.

Genome Integrity Webinar series

A virtual forum organized by GiiN
Winter Spring 2024 – Seminars Calendar:
From 5 to 6PM Rome, ZOOM link: https://uniroma1.zoom.us/j/95149984403

Calendar 2024

For more information contact or visit:
Twitter: GenomeIINetwork
GenomeIntegrityItaly@gmail.com
https://genomeintegrityita.wixsite.com/giin

Telomeres as a target of a potential innovative therapy for the 10-15% of intractable tumors

A possible therapeutic solution for treating ALT tumors has been identified in the IFOM laboratories, which include for example glioblastoma and osteosarcoma and against which chemotherapy and radiotherapy are not very effective. It is a therapy based on Antisense Oligonucleotides that acts on RNAs that promote the longevity of cancer cells of this type of tumor. The study, recently published in Nature Communications, was supported by the AIRC Foundation.

Ilaria Rosso, Corey Jones-Weinert, Francesca Rossiello, Matteo Cabrini, Silvia Brambillasca, Leonel Munoz-Sagredo, Zeno Lavagnino, Emanuele Martini, Enzo Tedone, Massimiliano Garre’, Julio Aguado, Dario Parazzoli, Marina Mione, Jerry W. Shay, Ciro Mercurio & Fabrizio d’Adda di Fagagna
Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs
Nat Commun. 2023 Nov 4;14(1):7086. doi: 10.1038/s41467-023-42831-0

IGM former student seminar – Giulia Monticone

Tuesday, November 21th, 2023

Aula “A.Falaschi” IGM LLCS di Pavia

Time 15:00

Giulia Monticone

Louisiana Cancer Research Center at LSU Health Sciences Center, New Orleans (US)

 

 

It’s time to wake up: awakening protective immunity with adenosine-based immunotherapy

Maria Michela Pallotta: new researcher at IGM

It is a pleasure to welcome Maria Michela Pallotta to our team at the Institute of Molecular Genetics of the CNR in Pavia. Maria Michela joins us as a researcher in the PNRR call “One Health Basic and Translational Research Actions addressing Unmet Needs on Emerging Infectious Diseases,” with a focus on the topic “Emerging Infectious Diseases,” under the guidance of Dr. Giovanni Maga.

Maria Michela completed a doctorate at the University of Naples Federico II, studying the neurotoxic and genotoxic effects of the exposure to the organophosphate pesticide Chlorpyrifos.

In recent years, she has continued her research activity at the ITB CNR in Pisa, focusing on the role of cohesin in tumor pathologies and rare diseases.

In 2023, Maria Michela obtained a prestigious ITB-CNR Seed Grant as Principal Investigator, with a promising project entitled “Cohesin Mutations and Wnt Agonism: A New Therapeutical Approach for Cancer.”

We are excited to welcome her to our research community and look forward to seeing what innovative contributions she will bring to our institute. Welcome, Maria Michela!

IGM former student seminar – Cristina Belgiovine

Tuesday 10 OTTOBRE 2023

Aula “A.Falaschi” IGM LLCS di Pavia

Time 14:30 

 

Cristina Belgiovine

Università di Pavia – Policlinico San Matteo Pavia Fondazione IRCCS

 

 

Role of immune response in tumor and prosthetic microenvironment

FIS call: Dr. DANA BRANZEI awarded an advanced grant in the ERC Life Sciences sector

With the publication of the rankings on 31 July, the evaluation procedure for the projects of the Italian Science Fund of the Ministry of University and Research, FIS 2021, was concluded. The FIS call aims to support fundamental research projects at national level, similar to those funded by the European Research Council (ERC).

Thanks to a budget of 50 million euro, 25 Advanced Grants were funded for amounts up to one and a half million euro each, intended for established Principal Investigators, and 22 Starting Grants for amounts up to one million euro each, intended for Principal Junior Investigators, who have not obtained their doctorate for more than 10 years.

In total 47 projects out of 1912 presented with a success rate of 2.5%.

Dr. DANA BRANZEI (Institute of Molecular Genetics Luigi Luca Cavalli-Sforza, Pavia) was awarded an advanced grant in the ERC Life Sciences sector with the project entitled: Replication-associated cohesion and recombination.

Dr. Branzei, born in Romania, after obtaining her degree and doctorate in Japan, moved to Italy where in 2008 she became PI at IFOM in Milan. She has won numerous international grants including an ERC Starting Grant (2009-2014) and an ERC consolidator (2016-2021) thanks to which she obtained the position of first CNR researcher in 2019. Since 2022 she is CNR Research Director and she is an EMBO member. She obtained prestigious international awards. Her scientific interests mainly concern: 1) understanding the origins of chromosomal instability in eukaryotic cells following replicative stress and 2) how genome replication is coupled to the spatial organization of DNA in the cell nucleus. She has published 91 papers on prestigious international journals including only  3 Nature communications, 1 Science, 1 PNAS and 2 Genes and Development in the last 3 years.

SARS-CoV-2 damages DNA and causes cellular aging and inflammation

Although several progresses have been made in terms of diagnosis, treatment and prevention since the first cases in December 2019, it is still not clear why SARS-CoV-2 has such a dramatic impact on human health compared to other respiratory viruses. The IFOM group led by Fabrizio d’Adda di Fagagna, specialized for 20 years in the study of the DNA damage response, a fundamental process through which the cells of our body protect us from the deleterious effects of various physiological and pathological events, including cancer and viral infections, discovered one reasons that make this virus particularly aggressive and the results are published today in the authoritative scientific journal Nature Cell Biology.

 

“All viruses are parasites, you know. – explains Fabrizio d’Adda di Fagagna, head of the IFOM laboratory “DNA damage response and Cellular Senescence” and Research Director at IGM-CNR of which he coordinates the IGM Research Unit at IFOM – They enter a cell and begin to exploit everything made available by the infected cell in order to replicate and spread. SARS-CoV-2 is a particularly greedy and skilled virus. In our laboratory we wondered how this “hacking” operation by the virus takes place and whether there is a connection with those processes that we study every day in pathological areas that only apparently look distant, such as tumors, genetic diseases and age-related disorders: all events, in fact, tightly associated with DNA damage accumulation”.Given these postulates, the first authors of this study Ubaldo Gioia and Sara Tavella, through the use of different in vitro cellular systems, have identified the molecular causes underlying the deleterious effects of COVID-19, and have found confirmation in vivo, both in mouse model systems of infection and in post-mortem tissues from COVID-19 patients.

 

What we have observed – Gioia and Tavella illustrate – is that SARS-CoV-2, once in the cell, hijacks its fundamental processes, forcing it to stop producing deoxynucleotides, the building blocks of DNA, to make it produce ribonucleotides, i.e. the “bricks” necessary to synthesize the RNA of the cell and that of the virus above all. It is precisely this alteration of the cellular processes carried out by the virus to its advantage that allows the explosive viral replication within cells infected by SARS-CoV-2. A dramatic consequence of this exploitation of the cellular machinery by the virus is the lack of deoxynucleotides: “the cell – the researchers describe – cannot adequately replicate its DNA and accumulates damage in its genome. Furthermore – continue Gioia and Tavella – we discovered that the virus, in addition to causing DNA breakage due to lack of deoxynucleotides, also interferes with the cellular repair mechanisms of such damaged DNA, inhibiting 53BP1, a protein essential for the repair process”.

 

These two events, DNA damage generation and inhibition of its repair, have dramatic effects on the cell infected with SARS-CoV-2 and on patients “Among them – explains d’Adda di Fagagna – certainly the premature aging of cells, a process known as cellular senescence, and the associated production of inflammatory cytokines. It is no coincidence that the main cause of the most severe symptoms in patients with COVID-19 is precisely an excessive production of inflammatory cytokines, also known as ‘cytokine storm’. Based on the results obtained, we have highlighted how the accumulation of damage to DNA, the only irreplaceable component of our cells, can make an important contribution to the inflammatory storm unleashed by the virus”. But the researchers didn’t stop there. “By providing the infected cells with deoxynucleotide supplements – explain Gioia and Tavella – we have shown that, by reducing the DNA damage caused by the virus, we also reduce the levels of inflammation”.“It is important to underline – concludes d’Adda di Fagagna – that cellular senescence and chronic inflammation are the basis of the aging process and in fact many scientists are more and more frequently gathering evidence of accelerated aging in patients with severe COVID-19. In this sense, it will also be important to study the correlation between our new discoveries and conditions such as the so-called long COVID, to develop new pharmacological treatments that limit the effects of this pathology.” 

This study would not have been possible without the collaboration of the ICGEB laboratories of Trieste (Alessandro Marcello and Serena Zacchigna) and of the San Raffaele Hospital of Milan (Matteo Iannacone), of the University of Padua (Chiara Rampazzo), of the Besta Neurological Institute (Paola Cavalcante) and the University of Palermo (Claudio Tripodo).

 

SARS-CoV-2 infection induces DNA damage, through CHK1 degradation and impaired 53BP1 recruitment, and cellular senescence.

Gioia U, Tavella S, Martínez-Orellana P, Cicio G, Colliva A, Ceccon M, Cabrini M, Henriques AC, Fumagalli V, Paldino A, Presot E, Rajasekharan S, Iacomino N, Pisati F, Matti V, Sepe S, Conte MI, Barozzi S, Lavagnino Z, Carletti T, Volpe MC, Cavalcante P, Iannacone M, Rampazzo C, Bussani R, Tripodo C, Zacchigna S, Marcello A, d’Adda di Fagagna F.Nat Cell Biol. 2023 Mar 9. doi: 10.1038/s41556-023-01096-x. Online ahead of print.PMID: 36894671