Dr Godinho Ferreira is established as a group leader at IRCAN, which he joined in 2019. He is working on telomere shortening in cancer and aging. The Canceropôle met him to discuss about his career and his current projects.

What is your career path and why did you choose to establish your lab at IRCAN?
I graduated in Portugal and did my PhD in London, studying DNA replication and cell cycle regulation. I went on to work as a post-doc on telomeres and DNA repair mechanisms, first at the University of Colorado in Denver (USA) and then at the Cancer Research UK London Research Institute (UK), an institute hosting both fundamental biologists and cancer research groups. This setting was very inspirational to me, appearing as a great way to understand the basis of the disease. I started my own research group in 2006 and I was based for 12 years at the Instituto Gulbenkian de Ciência, in Portugal.

After this time, I decided to take a new challenge and move to another environment. Beyond science, my passion is to discover and interact with different cultures. I was keen to join an institute dedicated to Cancer and Aging, and chose the IRCAN because of this specificity. We are now 7 people in the group, and have established a zebrafish facility (PEMAV) that is open to all!

Can you tell us more about your installation in the region?

Coming to France was a real challenge. I previously had no contact with the French system, and very few contacts with the community. I had very positive experiences, but also faced some difficulties. Recruiting people here was challenging for me, as understanding where to apply for funding was not the easiest. Knowing the community and the local system is important, and the Canceropôle was a great help for that. Indeed, the information available from the Canceropôle through the newsletter, the website and the “informatives” are really helpful (lists of calls available, scientific news from the community, events…). The annual seminar is also a great get together for the community, and I am looking forward to participating this year and meet other researchers from the region.

What are your scientific interests?

I have always been interested by the molecular mechanisms underlying genome protection. My research focuses on understanding how cells process and respond to damaged DNA occurring within chromosomes, particularly, at telomeres, and how this process is deregulated in cancers.

Strikingly, the incidence of cancer increases with age. To me, this is still one of the most interesting questions in biology. What could dictate this rise of cancer incidence with age? Although many researchers brought some insights, this question remains largely unanswered. For me, studying telomere is an entry point to try to solve this enigma, as they are linked to both aging and cancer. Indeed, human telomeres shortens with age. The study of patients with telomeropathies (rare genetic diseases characterized by short telomeres) strengthen the idea of a link between telomere shortening and aging. Indeed, these patients develop premature aging features at a young age, including increased cancer incidence.

In this context, my main interest is to understand why cancer increases with age, focusing on the contribution of systemic telomere shortening.

Which models do you use to answer these questions?

I chose my model system to the biological question I wanted to answer, the main one being: what are the consequences of telomere shortening in humans?

For this, I chose to work with zebrafish, as the impact of telomere shortening is closer to humans. Indeed, we could show that zebrafish telomeres also shorten with age, unlike mice telomeres that remain extremely long in old animals. We have shown that mutation of telomerase in zebrafish also induce a premature aging. Interestingly, much like other age-associated phenotypes, telomerase mutant zebrafish anticipate the onset of cancer to younger ages, similar to what happen in humans.

Currently, we use a zebrafish melanoma model that recapitulates the occurrence and progress of the human disease. We have shown that inducing telomere shortening in remote tissues, but not in cancer cells, accelerates the onset of the disease. Therefore, systemic telomere shortening, as it occurs during aging, causes an increase of cancer incidence.

Can you tell us more about your current and future projects?

We work on the hypothesis that the increase of cancer development with age or in premature aging models happens in a non cell-autonomous manner. In this context, we are now studying the communication between cells bearing short telomeres and neighboring cells that will be at the origin of cancer.

We are developing 2 main projects:

  • An « aging project », funded by an « équipe FRM » grant. Starting from the observation that some organs decline faster and display short telomeres earlier than others, such as the intestine. We restored telomere length specifically in the intestine and showed that intestine-complemented fish recover from aging phenotypes and live a longer lifespan. This work, currently in review for publication, showed that communication from short telomeres in a specific organ affects cancer incidence in other parts of the body.
  • A « cancer project », funded by an INCa PLBIO grant starting this year. We investigate the role of short telomeres in cancer progression. The hypothesis is that cells with short telomeres become senescent and communicate, inducing a systemic inflammation that will then promote the onset of cancer in remote tissues. Again, we are investigating here the function of short telomeres signaling in a non cell-autonomous manner.

Our projects are well integrated within the institute activities, and we also have collaborative work ongoing, including projects that will take advantage of our zebrafish models to test the effects of anticancer drugs. This will include using standard therapeutic molecules on prematurely aged animals, and testing if a combination with the inhibition of short telomeres communication impacts their effect on cancer progression. This work is done in collaboration with Dr J. Goetz in Strasbourg and Dr Y. Collette from Marseille.

I am looking forward to discussing about our projects at the Canceropôle Annual Seminar (5th & 6th July, 2022) and to connecting with all members of the regional scientific community.