Giorgia La Barbera

Project title

Elucidating the role of gut microbiota in colorectal cancer with DNA adductomics-CROMICS

What is your project about?

The project is about studying the role of gut microbiota on colorectal cancer initiation with a new powerful technology called DNA adductomics. 

Colorectal cancer is the second leading cause of cancer-related deaths worldwide and represents a significant health concern. Despite advancements in diagnosis and treatment, understanding the underlying mechanisms of colorectal cancer remains a critical research challenge. The gut microbiota and its metabolites might play a crucial role by interacting with the colonic epithelium, chemically modifying DNA, and forming DNA adducts.The main purpose of this project is to apply my new DNA adductomics methodology on colon tissues from patients with colorectal cancer, to identify microbial metabolites causing DNA adduct formation, and thus increasing cancer risk.

How did you become interested in your particular field of research?

Since I was a child, I have always loved science. I collected minerals, I was interested in earthquakes, volcanos, dinosaurs, and I loved learning how the human body works. I also enjoyed puzzle games that challenged my brain. Growing up, I realized that I was very excited to study life in detail, and I decided to become a chemist. I now have more than 10 years’ experience identifying unknown molecules using high-resolution mass spectrometry (HRMS). Solving molecular structures from their mass spectral fragmentation feels like solving a puzzle. In recent years, I applied HRMS to study metabolites with beneficial or harmful health effects. In 2019, I received a Marie Curie Individual Fellowship to develop the first DNA adductomics method using HRMS to identify carcinogenic molecules in colon tissues - this is the method I will use in the Sapere Aude: DFF-Research Leader-grant.

What are the scientific challenges and perspectives in your project?

DNA adductomics itself might not be enough to elucidate the role of gut microbes in colorectal cancer, and that is why I will use it in combination with the analysis of the gut microbiota and of the microbial metabolites by metabolomics. 

Firstly, I will provide a comprehensive view of DNA adducts in a cohort of patients with colorectal cancer or in patients predisposed to develop colorectal cancer. New DNA adducts will be identified and correlated to gut microbes and their relative microbial metabolites to find potential causal links between specific gut microbes and cancer initiation. 

This will ultimately allow me to identify specific gut microbes and microbial metabolites increasing the risk for developing colorectal cancer. 

What is your estimate of the impact, which your project may have to society in the long term?

The project aims to uncover the role of microbial metabolites in colorectal cancer using DNA adductomics. Identifying previously unknown microbial carcinogens is the first step toward developing new preventive strategies. The discovered DNA adducts could help assess DNA damage in the colon and guide dietary interventions, such as testing how different diets or pre/probiotics affect adduct levels. The perspective is to move the field towards the development of personalized preventive approaches for cancer through tailored dietary and microbiota-modulating interventions. Since DNA adducts form at the earliest stage of cancer, I also aim to detect them in blood and urine to develop less invasive sampling methods and establish them as risk biomarkers for early cancer diagnosis.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The Sapere Aude: DFF-Research Leader-grant will allow me to build my own research group and position me in an important niche of research with high potential in the field of cancer research. My vision is to establish a research group whose unique quality will be its ability to exploit the synergy between metabolomics and DNA adductomics to elucidate cancer causes and mechanisms. The grant will allow me to maintain my current position in the emerging and internationally attractive research field of DNA adductomics, and it will also provide a strong offset for further applications, since it could provide new ground-breaking insights into colorectal cancer initiation. I am looking forward to starting my first research group in DNA adductomics and transmit my passion to the next generation of young researchers.