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PhD Defence Interview – Fábio Rosa

Portrait of Fabio Rosa and his thesis cover
Fábio Rosa will be defending his PhD thesis on Thursday 10th June 2021.

During his studies, PhD student Fábio Rosa has been developing strategies to generate dendritic cells by direct reprogramming. Merging cellular reprogramming with immunology, this research takes new steps towards the development of novel cancer immunotherapies. Defending his thesis on June 10th, in this interview Fabio tells us about his research and time spent at Lund Stem Cell Center.

Can you tell us about the research during your PhD?

I’ve been working in the Pereira group at the intersection of two huge research fields: immunology and direct reprogramming. The overall aim of my research has been to develop new strategies for the conversion of non-related somatic cells into dendritic cells, key orchestrators of immunity. Dendritic cells detect foreign entities – such as viruses, bacteria and even cancer cells – and present their antigens to other effector cells of the immune system, inducing a targeted immune response. We aim to use our knowledge to design novel strategies for regenerative medicine and cancer immunotherapy.

I began by identifying transcription factors crucial for dendritic cells. This was achieved via a screening approach, where I asked which factors are highly expressed in this cell type, as well as those that have a dramatic impact on the dendritic cell family when knocked out. The next step was to test different combinations of these factors in fibroblasts to develop a protocol to directly convert them into dendritic cells.

These studies were performed using embryonic fibroblasts from a reporter mouse, acquired from our collaborator Caetano Reis e Sousa at The Crick Institute, London. In this model, dendritic cells fluoresce red. We used fibroblasts (not red) from these mice and identified a combination of three transcription factors able to convert these cells to dendritic cells (red). The cells generated recapitulated the gene expression profile and functionality of a very rare sub-population known as type 1 conventional dendritic cells, that play a unique role in the control of tumor growth.

The remainder of my PhD was focused on optimising this reprogramming protocol in a human setting. I applied single cell analysis to explore the dendritic cell reprogramming process and identify factors or pathways correlated with successful reprogramming. I identified a number of cytokines and alternative expression systems that resulted in the reprogramming of human cells at high efficiency. Moreover, I collaborated with AstraZeneca and SciLifeLab to develop a high content screening workflow, enabling the identification of chemical compounds that increase reprogramming efficiency or replace the action of individual transcription factors.

During my studies, I was also involved in the incorporation of Asgard Therapeutics, along with Cristiana Pires and my supervisor Filipe Pereira. It is our aim to use the reprogramming protocols developed in our lab to advance the first cancer immunotherapy based on direct cell reprogramming.

How did you end up doing a PhD in Lund?

I joined Filipe’s lab as a Masters student whilst he was a principal investigator at Coimbra University in Portugal and continued to a PhD.  I arrived at the lab one day and Filipe called me into his office. As I entered the room I remember noticing some flyers about Lund University lying on a table in his office. Filipe asked me to sit down and proceeded to explain that “This is a very good university, known for numerous Nobel laureates and with a very strong component in terms of innovation.”  I was wondering where he was going with this, and then he told me about the fantastic offer he had received from the Wallenberg Foundation to start his own group. Filipe asked if I would like to join him and continue my project in Lund. It was a great opportunity for me and I’m happy I took it.

What has been the most challenging aspect of your PhD?

Finding a good balance can be tricky, but it’s achievable if you have a good team. Within our research group we all collaborate to achieve the same goals and develop our research projects. Within the Asgard Therapeutics team, Cristiana is the CEO and as the main hands-on person, she does a fantastic job and without her and Filipe it would be very difficult.

If you have additional entrepreneurial activities during your PhD you cannot expect to have the same schedule as a normal student. You have to sacrifice some of your free time - which is not a problem for me as I really enjoy it!

What have you found the most valuable during your PhD in Lund?

There are many things, and it depends on the perspective. In terms of science, here in Lund we have access to fantastic core facilities, with state-of-the-art equipment. Lund University Bioimaging Centre (LBIC) in particular has helped us generating images vital for our research, science communication and also for the front cover of my thesis - a 3D rendering from scanning electron microscopy.

Within our division, research groups interact on a day-by-day basis, which leads to a lot of opportunities to collaborate. In addition, Lund is a very international university, which has allowed me to broaden the spectrum of people I know. This has definitely contributed to my growth as a researcher.  

Finally, from the entrepreneurial point of view there is a very rich environment in terms of innovation and startup companies at Lund University.

What are your future plans?

Good question! I’m a very open minded person. I love academia but I also really like industry and translation. For now, I can say that I will most probably start working full time at Asgard Therapeutics to push forward our translation efforts. Exciting news is on its way!

 

Fábio Rosa will be defending his PhD thesis “Generating Dendritic Cells by Direct Cell Reprogramming. Merging cellular reprogramming with immunology towards the development of novel cancer immunotherapies.” on Thursday the 10th of June at 09:00 in Segerfalksalen, BMC A10, Sölvegatan 17, Lund.

Click here for the Zoom link

His opponent is Professor Thomas Graf, Center for Genomic Regulation, Barcelona, Spain.