Recently arrived in the region, Dr Pilar Dominguez is establishing her lab at the C3M institute in Nice after being awarded a Chair of Excellence at the Université Côte d’Azur. She is telling us about her scientific background and the projects she is planning to develop at the C3M.
Can you tell us about your career and how you ended up setting your lab in Nice?
I did my PhD in Madrid, Spain, where I studied basic immunology and focused on the function of dendritic cells in inflammation. I then moved on to do a first post doc in New York, USA, at the Weill Cornell Medical College, where I was introduced to cancer research.
My immunology background was useful for the project and I started to work on epigenetics, to decipher the involvement of the TET2 enzyme and DNA methylation in B cell lymphoma. This work was mainly fundamental research, but with a translational opening that appealed to me. I thus joined the Peter MacCallum Cancer Center in Melbourne, Australia, to continue my projects but with a strong translational component. I studied the effect of epigenetic modulation (using specific inhibitors or genetic modification) in preclinical models of blood cancer. The setting was really interesting for the development of my research, since the Center was located in a hospital and I could benefit from the close proximity of the clinicians and patients. Indeed, I had the opportunity to work with clinicians and also a group of patients that helped a lot to communicate my results, but also to understand what it is important from the patient side and to improve my grant application writing. It was an important support that put things in perspective and make what we do in research count.
After that, I started to look for an independent position as a group leader, and I wanted to come back to Europe. I applied for the great opportunity in Nice with the Labex SignalLife Program and got a Chair of Excellence at the Université Côte d’Azur, to continue my work on blood cancer combining epigenetics and immunology. I am now based at the C3M since a month ago, and I am currently setting up everything to get the lab starting!
Could you tell us more about your current and future projects?
In Australia, my work was dedicated to better understand the biology of lymphoma and leukemia, but also to the optimization of epigenetic based therapies for these diseases. For that, I studied the effect of combining drugs already in use in the clinics, and collaborated with pharmaceutical companies to do preclinical studies on new compounds still in development.
I am now expanding this type of research to:
- 1) define the mechanisms underlying the development of lymphoma caused by epigenetic deregulation and better understand the disease.
- 2) improve the efficacy of therapies based on epigenetic drugs, with the long-term goal to suggest new therapeutic approaches.
I will work on the biology of the tumor cells themselves, but also on the microenvironment as it is strongly affected by the drugs and is an important component of the cancer biology and response to therapy. I will particularly look at the innate immune system.
In terms of epigenetic targets, I will first focus on the function and modulation of DNA methylation agents and Histone Deacetylases inhibitors, but many other epigenetic modifiers are involved in cancer processes and I am planning to expand my research in the future. The epigenetic field is evolving very fast, with new inhibitors constantly proposed mainly to improve their specificity of action.
What type of techniques and methods do you use in your research?
I combine different approaches to be able to answer the questions I am interested in. I work with primary samples and mouse models, and use state-of-the-art technologies in genomics, epigenomics and transcriptomics.
I will use mouse lines and patient derived-organoid models that I previously developed to conduct my future projects. I set up mouse models mutated in epigenetic proteins that develop lymphomas. Those are interesting to study the onset of the disease, and elucidate the underlying mechanisms that are still not fully understood. The use of in vivo models allows to work on different cell populations in the organism, an interesting point for my projects on the tumor microenvironment. In parallel, I will use cellular models to do screening and find new interesting targets, and continue setting up organoids or xenograft approaches using patient samples.
In terms of read-outs, I use cutting-edge techniques to evaluate the epigenome and transcriptome status, such as ChIP-seq, ATAC-seq, RNA-seq… The technologies available in the field are challenging and evolving fast, which makes things interesting and allows researchers to get more and more specific information from the experiments. I am planning to use more recently developed techniques in the future, such as Cut&Run or Spatial Transcriptomics.
These approaches enable me to look at the consequences of mutations or the effect of drugs on the genome and the transcription. Although very powerful, the methods I use require a lot of specific analyses and skills to integrate the data obtained from different type of experiment to reach a conclusion. I need to collaborate with bioinformaticians for those aspects, always keeping in mind the biological question and what we want to know from the data, which is a crucial point in the analysis process.
How is your installation in the lab and in the region going?
The installation of the lab is going well, I am now waiting for some of my animal models to arrive. I have a starting package coming with the Chair position that enables me to start working, and will apply for other grants to fund all my projects. I have a master student, and I will recruit an engineer and a PhD student this year. The close proximity of the hospital makes it easier to combine basic research and clinics, and I think my projects and expertise are fitting really well within the institute. I already published with a national group in the past, and I have started to interact with others at the C3M.
I really like the city, it is a beautiful place to be, with the perfect size for my taste! The scientific environment is great and stimulating, with the University growing and several institutes around. I look forward to interacting with local researchers and develop collaborations, something I already started for the bioinformatics with UCA groups. Being based in Europe is also important for my research, since I will have the opportunity to develop collaborative projects with groups in France and nearby countries, as everything seem closer!
To hear more about her projects, join us at the Canceropôle’s Annual Seminar where she will give a talk!