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Emmanuele Crespan


IGM-CNR, Via Abbiategrasso, 207 - 27100 Pavia, Italy

tel: +39-0382-546346

fax: +39-0382-422286 



Curriculum vitae

2004. Degree in Biological Sciences at the University of Pavia. 

2008. PhD degree in Genetic and biomolecular Science. Department of Genetics and Microbiology, University of Pavia 

2008-2011. Post-doctoral fellow, Italian Federation for Cancer Research  - FIRC. Institute of Molecular Genetics (IGM-CNR), Pavia. 

(2009). Visiting researcher at University of Zurich, Institute of Veterinary Biochemistry and Molecular Biology.



2008. Milano, Carlo Erba Foundation. Winner of the Cecilia Cioffrese Award for excellence in scientific research. 

2015. Roma, CNR. Young Researcher Scientific Award. 

Research Activity

RNase H2
With more than 107 ribonucleotides misincorporated in the human genome during replication, embedded ribonucleotides are the most abundant DNA lesions. The presence of the 2’-hydroxyl group makes misincorporated ribonucleotides prone to spontaneous hydrolysis, potentially resulting in the accumulation of strand breaks. Moreover, their presence may decrease the rate of DNA replication causing replicative fork stalling and, eventually, collapse. Ribonucleotide removal is initiated by Ribonuclease H2 (RNase H2), the key player in Ribonucleotide Excision Repair (RER). Its absence leads to embryonic lethality in mice, while mutations decreasing its activity cause the severe phenotype of the Aicardi–Goutières syndrome.
We are interested in the identification of factors that participate in RER using biochemical and cell biology approaches. We are also focusing our attention on the ability of RNase H2 to process ribonucleotides embedded in non-canonical DNA form and in the development of tools to map ribonucleotide embedded in the genome, with the aim to identify cold and hot spots for their misincorporation.

Alternative Lengthening of Telomeres

About 10% of cancers do not rely on telomerases activity as maintenance mechanism of telomeres (TMM), but on an alternative lengthening of telomeres (ALT) pathway. ALT-proficient cells show common features such as heterogenic and fluctuating telomere lengths, high levels of telomere recombination events, and abundant extrachromosomal telomeric repeat DNA. Despite a comprehensive view of the factors and the molecular mechanisms involved in ALT is still missing, mounting evidence led to a consensus on repair of double strand breaks (DSBs) originated from replication forks collapse as the leading cause of ALT. A homology directed process, involving the invasion and elongation of G-rich strand using the complementary strand as a template is also a consolidate characteristic of ALT mechanism. Different pathways has been proposed to explain TMM in ALT, all of which require enzymes able to catalyse DNA strand transfer and annealing reactions followed by DNA synthesis. So far, the identity of the DNA polymerases (Pols) involved in the elongation step of ALT has remained elusive.
By using multidisciplinary approaches (including biochemistry, cell biology, proteomics, imaging, CRISPR libraries, and animal models) we investigate of the roles of specialised DNA polymerases in ALT mechanism and, in general, in the reconstruction of the molecular steps occurring in ALT initiation. The goal of this research is the identification of enzyme(s) essential in ALT process that to be considered as targets for new therapeutic approaches.


Co-occurrence of cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS) is a rare, adult-onset, slowly progressive neurological disorder characterized by imbalance, sensory neuropathy (neuronopathy), bilateral vestibulopathy, chronic cough, and occasionally autonomic dysfunction. The genetic cause of the disease was very recently discovered and consists of biallelic AAGGG repeat expansions in the second intron of replication factor C subunit 1 (RFC1). The mechanism leading to symptoms onset is not yet understood.
To understand the mechanism driving CANVAS onset, we aim to characterize RFC1 activity on CANVAS derived patient cell lines through biochemistry and cellular based assays.

Repair DNA polymerases.
DNA repair is crucial to maintain genomic stability, with eepair DNA polymerases, as well as translesion polymerases playing a pivotal role. We have focus our attention on the study of the enzymatic properties and cellular roles of DNA polymerases in response to DNA damage in an attempt to identify specific activities and molecular processes that could be targets for innovative therapies. In particular, we identified and characterized selective inhibitors of specific polymerases, including compounds that can be incorporated specifically against certain types of DNA damages, such as abasic sites, to be used as markers for these lesions. The same research has led to the elucidation of the role of repair polymerases and other accessory factors for the faithful bypass of various lesions. In particular, we found that DNA polymerase Lambda is specifically recruited for the faithful bypass of the mutagenic, and most common oxidised lesion, 8-oxoG.We also explored the contribution of repair polymerases in the expansion of tri-nucleotides repeats that are characteristic of different neurodegenerative diseases, suggesting a possible role of polymerase beta in Poly-Q disorders.
Drugs development.
Part of our research is focused on the characterization of new inhibitors of molecular targets involved in viral, neurodegenerative, and neoplastic diseases. In particular, we are interested in the evaluation of the inhibition potency, toxicity, and mechanism of action of new drug candidates through in vitro assays using recombinant proteins as well as cellular models. We have been involved in the characterization of molecules targeting essential factors in the replication of different viruses including HIV-1, HCV, Zika Virus, enteroviruses, and Dengue virus. We are also collaborating with several groups on the evaluation of small molecules as inhibitors of kinases responsible of the onset and progression of specific cancers or targets of viral or bacterial infections (host targets), or involved in neurodegenerative diseases progression.



Publications: Link

ORCID ID: 0000-0003-0597-6929

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