Diving into ancient oceanic life forms
Turquoise water, breezy warm air, and the soothing sound of sea waves as they wash over the sand before retreating into a colourful underwater world.
It’s no surprise that Dr. Federico Gaiti, who grew up in Reggio Emilia, Italy, a country surrounded by the beautiful Mediterranean Sea, developed a passion for scuba diving and marine biology.
“I became more and more interested in why we have such stunning diversity of colours and forms underwater,” says Federico, who completed his Bachelor’s and Master’s degrees at the University of Bologna. Mediterranean bluefin tuna, sea anemones, jellyfish, and sponges—not only were they companions for his scuba diving adventures, but they also became central to his research.
His quest to trace the origins of multicellular life led him to the southern hemisphere, where Federico pursued a PhD in Evolutionary Biology and Genomics at the University of Queensland, Australia. The Great Barrier Reef, with its unparalleled diversity of life forms, provided a wonderful opportunity to peek into the ocean’s evolutionary secrets—and eventually led to his career in cancer.
“Life began as single-celled organisms and gradually evolved into complex, multicellular forms. Cancer, on the other hand, seems to reverse-engineer this evolutionary journey,” says Federico.
During his PhD, he studied marine sponges, one of Earth’s most ancient groups of multicellular animals, along with jellyfish, corals, anemones, etc. “In multicellular animals, cells cooperate and specialize in different functions to maintain a harmonious system,” he explains.
“But cancer cells lose this ability—they behave more like single-cell organisms. They prioritize their own survival, proliferate uncontrollably, and lose specialized functions, often reverting to a more primitive, undifferentiated state. Much like single cells adapting to new environments, cancer cells evolve rapidly to withstand external pressures, such as therapy.”
Evolution of tumour cells
“It felt like a natural next step to blend my background in evolutionary biology with a drive to tackle problems that directly impact human health.” Federico shifted toward human-centred biomedical research during his postdoctoral studies at Weill Cornell Medicine in New York.
Now, instead of studying the separation of single-celled organisms and marine sponges, Federico focuses on mapping the evolutionary family trees of tumour cells to better inform cancer development and progression.
An edge he gained from his “past life” is a deep understanding of how genes are regulated within cells, namely the study of epigenetics. This includes regulatory elements like non-coding RNAs, DNA methylation, and chromatin marks. In his earlier work, he had previously used this knowledge to identify how the regulatory genome has evolved across different animal species. Today, he needs to determine how these same regulatory mechanisms change between different lineages of cancer cells.
With Dr. Dan Landau, a leading expert in cancer evolution, Federico unravelled that, in both leukemia and gliomas, epigenetic changes accumulate within cells, driving tumours to evolve. These changes contribute to the tumour’s diverse and uneven cellular makeup over time.
Gliomas are hard-to-treat tumours that affect the central nervous system including the brain and spinal cord. The team found in gliomas, there are distinct cellular states, driven by specific epigenetic changes that are important for the tumour to develop.
One such state involves malignant cells regressing into a more primitive state, resembling neural progenitor cells—a type of cells that are close to stem cells, undifferentiated, and can self-renew.
“When malignant cells revert to this more primitive, undifferentiated state and acquire stem cell-like features, they become the fuel for the tumour growth,” Federico adds, “We found that these epigenetically-encoded cell states are inheritable—one cell in this state can propagate its lineage and contribute to the cancer progression process.”
Differences in DNA methylation, a particular chemical modification of the cells’ DNA, give rise to these various cellular states, and affect which genes the cells can transcribe and express. To decode these complex layers of gene regulation, Federico used a method called multiomics single-cell profiling, which looks at each individual cell from patient glioma samples, and creates a profile of their DNA methylation, transcriptome, and genotyping information. He coupled this analysis with a method to trace and differentiate cancer cell lineages and eventually mapped the evolutionary family tree to understand how different glioma cells are related and change over time.
“Studying how tumour cells evolve from early onset to a more developed stage can give us insights on how to intervene early and how to prevent cancer progression,” Federico says.
Federico brought his interests and expertise to the Princess Margaret (PM) where he continues to explore how malignant glioma cells evolve while invading normal brain tissues. Collaborating with other scientists at PM, his team is broadening the use of this integrative method to investigate cell diversity and evolution in various other cancers, which will help develop targeted therapies for early detection and prevention.
A new chapter as an independent researcher
The rising star in single-cell cancer biology moved to Canada and established his lab at PM in 2021, a move that brought both exciting opportunities and new challenges for Federico.
“Becoming an independent researcher and leading a lab introduced me to new experiences that I hadn’t encountered before,” says Federico, “I am fortunate to have great mentors at PM, such as Drs. Mark Minden and Vuk Stambolic, who continue to guide me through the highs and lows of this new role. Their senior mentorship serves as a strong example that helps me at times when I mentor my own trainees.”
Federico leans on his communication skills to lead a multidisciplinary research team. “Everyone is unique in their own way. They can have different backgrounds, skill sets and communication styles. Being approachable and listening attentively have helped me adapt my mentorship approach to fit each trainee’s unique needs.”
Meet PMResearch is a story series that features Princess Margaret researchers. It showcases the research of world-class scientists, as well as their passions and interests in career and life—from hobbies and avocations to career trajectories and life philosophies. The researchers that we select are relevant to advocacy/awareness initiatives or have recently received awards or published papers. We are also showcasing the diversity of our staff in keeping with UHN themes and priorities.