“We approach the study of paediatric tumours from different angles with the ultimate goal of developing more personalised and less aggressive treatments”

Since then she has been working on and defining the research lines and scientific goals of her new Paediatric Cancer Epigenetics group, which has recently become a part of the Paediatric Cancer Programme. We spoke with Dr Avgustinova to learn more about her past research and her new group's objectives.

How did your scientific career begin?

I graduated in Biology from Oxford University in England and from the start of my training I knew that I was interested in molecular and developmental biology. My scientific career probably began in my early weeks at university, when my tutor recommended a book that inspired me. It was The Selfish Gene by Richard Dawkins, which discusses evolution and natural selection on the level of the gene, rather than the individual.

What relation did Dawkins's book have to your beginnings in cancer research?

The concepts which it presented made it clear to me that natural selection at the level of cells and genes would play an important role in the biology of cancer. Thus began my fascination with the study of the origins of cancer, the metastatic processes and the response to treatment. Fundamentally, natural selection underlies all of these processes, although the exact mechanisms are poorly understood. This is drove me to carry out my doctoral studies at the Institute of Cancer Research in London.

On what aspect of cancer did you focus your doctoral thesis?

My PhD project focussed on the mechanisms of metastasis in breast cancer. We know that in adult cancers, metastasis is one of the factors that leads to poor prognosis, and thus by choosing to study the processes that underly metastatic spread I hoped to discover something that could contribute to improving patient prognosis and wellbeing.

After obtaining your doctorate, you moved to Barcelona to begin a new phase of activity at IRB Barcelona. What did you work on there?

Part of my work as a postdoctoral researcher in the laboratory of Dr. Salvador Aznar Benitah focussed on the mechanisms of metastatic spread of oral squamous cell carcinoma, but I also started to work on epigenetics. Epigenetic processes are what determines the fate and function of each cell in our body: the genetic information in all the cells in our body is identical, and it is epigenetic processes that define cell types as diverse as blood and skin cells. In recent years we have learnt that deregulation of epigenetic processes  plays an important role in the development of many cancers.

Up to then you had been conducting all your research on adult cancers. What led you to begin research on paediatric cancer?

My first exposure to the world of paediatric cancer was through Dr Jaume Mora, who contacted me after reading one of my scientific articles on the role of epigenetic processes in tumour initiation. Dr Mora believed that the questions and mechanisms I had studied could be important in the framework of childhood cancer, and after immersing myself in the scientific literature on developmental tumours, I completely agreed! Indeed, epigenetic deregulation is extremely common (yet very poorly understood) during the initiation of developmental tumours.

I presented my research at IRSJD and had some very interesting discussions with Dr Mora and other researchers from IRSJD. I learnt a lot from this encounter, including that the origins of adult and paediatric cancers are distinct, and that findings from the research in adult cancers cannot be directly transferred to children. We need to study childhood tumours as an independent entity, and my interest was immediately drawn to the biology of developmental tumour initiation.

What brought you to the Institut de Recerca Sant Joan de Déu?

During the encounter with the researches at IRSJD we found a lot of shared interests, ideas and concerns. I quickly realised the great opportunity that was before me: to transfer my knowledge and skill set to the study of developmental tumours, which are much less understood than adult cancers. Thus, my work could potentially bring about real change. Soon after, I joined the IRSJD as a researcher within the framework of the Paediatric Cancer programme, and never looked back!

You have your own research group, Paediatric Cancer Epigenetics, in the Paediatric Cancer programme. What are its goals?

The main goal of my lab is to understand the basic biological and epigenetic mechanisms that are deregulated in the process of tumour formation. This knowledge will help us identify new treatment strategies for patients with childhood cancer. We are actively looking for treatments that do not only improve survival, but also give a good quality of life. Cancer treatments can have many side effects, especially in a developing body, and it is therefore very important to understand the biology of each tumour to be able to offer personalised and tailored treatment to each individual patient.

Currently we are working on establishing and fine-tuning all the models and tools that we will be using in our research. This is an important and complex task, and I am very lucky to have a lot of support: Together with Dr Carlos Rodriguez, and more recently Àlex Cebrià, we are working on cell culture models established from PDX tumours provided by Dr Ángel Montero. Likewise, Dr Cinzia Lavarino has helped us with the molecular characterisation of the mutations of the models that we are establishing. With these models now established, we are in a great position to perform our research.

What difficulties or challenges do you face in conducting all these studies?

Luckily, developmental cancers are extremely rare. This, however, can be challenging when we try and study them, so we heavily rely on the use of good and well characterised models. To see the full picture of the disease, we have to combine many different techniques (cell culture, animal models, high throughput sequencing technologies), each of which captures only certain aspects of the disease.

Could you give us a specific example of a model that your group is working on now?

Right now, the work in the lab focusses on malignant rhabdoid tumours. We are working on repairing the main mutation that causes these tumours to study the resulting epigenetic changes. We are looking to answer a number of questions: How can these tumours originate in diverse locations? Which cell is the origin of the tumour? How do these epigenetic changes lead to tumour formation?

We will also work with transgenic animal models to be able to model an intact immune system. Lastly, we will perform in-depth molecular characterisation of tumours from the SJD Biobank.

Using these three different approaches we will gain a broad perspective of the biology that drives malignant rhabdoid tumour, which will allow us to identify new treatment approaches.

What would you describe as some of our research institute's outstanding features?

In addition to what I already mentioned, I see the close collaboration between the laboratory researchers and the hospital physicians as a unique and rare asset of IRSJD! In this setup I believe it is possible to see a treatment that has been developed in the laboratory be applied to patients in the hospital... for me, this was an opportunity that I could not miss!