Giorgia Alessio, PhD Candidate in Inflammation, Immunity & Cancer, Memorial Sloan Kettering Cancer Center, Dr. Andrea Ventura lab

Giorgia started her doctoral training in Prof. Vincenzo Corbo's laboratory in Verona, Italy, and is now in her third year at Memorial Sloan Kettering Cancer Center in New York, where she works in Prof. Andrea Ventura's lab. 

The Ventura group is dedicated to functionalizing the cancer genome, deciphering how genetic and epigenetic alterations in cancer cells drive tumor progression and shape therapeutic response. The lab pursues this mission through three interconnected research questions: (1) how chromosomal rearrangements fuel tumorigenesis and the emergence of drug resistance; (2) how oncogene amplifications mediated by extrachromosomal circular DNA (ecDNA) govern tumor evolution and metastasis; and (3) how non-coding RNAs orchestrate key biological processes, including tumorigenesis, tissue regeneration, and cellular homeostasis. A key strength of the laboratory is its expertise in generating and using sophisticated genetically engineered mouse models, precisely tailored to interrogate specific cancers and molecular targets. Critically, the group has pioneered both somatic and germline strategies to faithfully model cancer-associated mutations, including complex chromosomal rearrangements and focal amplifications, that were until recently beyond experimental reach.

RESEARCH PROJECT

Chromatin Remodeling and ecDNA Dynamics in Pancreatic Cancer

Extrachromosomal DNA (ecDNA) represents a structurally and functionally distinct class of genetic elements that exist outside canonical chromosomes and has emerged as a major driver of cancer evolution. Structurally, they are present as small molecules of double-stranded DNA and are particularly concerning because they can carry cancer-driving genes, such as MYC, in abnormally high copy numbers, accelerating tumor growth and therapy resistance.

Giorgia is investigating what sustains ecDNA in cancer cells. Her focus is ARID1A, a gene involved in chromatin remodeling that helps control how DNA is packaged and read. Early results suggest it plays a key role in MYC ecDNA-positive pancreatic cancers: when ARID1A was disrupted in cancer cells carrying MYC ecDNA, MYC levels changed significantly.

Now at Memorial Sloan Kettering Cancer Center, Giorgia is testing these findings in genetically engineered mouse models to answer a critical question: Does loss of ARID1A fuel ecDNA-based amplification, or does it suppress it? The answer could reveal a new therapeutic target in one of the hardest cancers to treat.

Prof. Andrea Ventura — Memorial Sloan Kettering Cancer Center, Host Laboratory

“We are deeply grateful to the Nadia Valsecchi Foundation for this support, without which it would have been extremely difficult to build this bridge between Italy and the United States. Their support has enabled Giorgia to join Andrea Ventura’s laboratory and to accelerate a research project that could not have advanced as quickly within the limits of a single institution. This opportunity allows us to take an observation first identified through patient data and test it in the sophisticated experimental models developed in Andrea’s lab. The Foundation has supported us in two decisive ways: first by helping create this connection, and then by investing in Giorgia’s work. We feel a strong responsibility to honor this trust through rigorous research and to give back to the community of scientists and patients.”

Prof. Vincenzo Corbo — University of Verona, Home Laboratory

We are deeply grateful to the Nadia Valsecchi Foundation for this support, without which it would have been extremely difficult to build this bridge between Italy and the United States. Their support has enabled Giorgia to join Andrea Ventura’s laboratory and to accelerate a research project that could not have advanced as quickly within the limits of a single institution. This opportunity allows us to take an observation first identified through patient data and test it in the sophisticated experimental models developed in Andrea’s lab. The Foundation has supported us in two decisive ways: first by helping create this connection, and then by investing in Giorgia’s work. We feel a strong responsibility to honor this trust through rigorous research and to give back to the community of scientists and patients.

Publications:
- Engineered extrachromosomal oncogene amplifications promote tumorigenesis, Pradella D. et al., Nature 2025
- MYC ecDNA promotes intratumour heterogeneity and plasticity in PDAC, Fiorini E. et al., Nature 2025

This project was awarded a grant of $80,000 by the Nadia Valsecchi Foundation.