(Vienna, 14.09.2020) Sabine Taschner-Mandl, PhD, aims to achieve a long-term benefit for children with cancer via research. She heads the Tumor Biology group at St. Anna Children's Cancer Research Institute and, on the occasion of Childhood Cancer Awareness Month September, explains how she is pursuing her goal and what it is that you really need to succeed in science. Among other things, it is important to be there with all one's heart and to stick to it even when things get complicated. Because there is one thing, you can rely on in childhood cancer research: It is more complicated than expected.
What are you currently working on?
The focus of my research group is very patient-, diagnostics- and therapy-oriented. Together with my colleagues, we perform the complete portfolio of genetic and bone marrow diagnostics for solid tumors in children, with the exception of brain tumors. By collecting liquid biopsies, we want to support physicians throughout Europe to determine whether a child is responding to treatment and how likely they relapse. The tumor releases genetic material into body fluids such as blood, also called liquid biopsies, which we can analyze. Using liquid biopsies, we aim to be one step ahead of the tumor to be able to apply early counterstrategies against more aggressive tumors, without the need for a stressful surgery for the collection of tumor tissue samples.
What other research questions do you pursue?
Another project focusses on children with neuroblastoma, who have particularly poor survival chances. Neuroblastoma, an often malignant disease of the nervous system, is the most common solid tumor in infants and young children. We are investigating such ultra high-risk patients in whom we do not yet know the molecular triggers in detail. Even though affected children often respond well to treatment, they frequently relapse or die from their tumor at a later timepoint. We want to know: What are the molecular mechanisms behind this? How can we intervene therapeutically?
How exactly are you planning to tackle this?
It is already known, that certain genetic changes are associated with poor prognosis. Now, we are looking very closely which individual genes and mechanisms are decisive for the aggressive behavior of the tumor. Using so-called CRISPR screens in cell lines, we switch off certain genes and then see whether a gene was important for the survival of the tumor cell. In each cell, we introduce another defect by switching off a gene. We can do this for all of the approximately 20,000 genes. If a cell dies, the affected gene may be a therapeutic target.
What makes it so difficult to treat cancer?
One aspect is certainly its heterogeneity. Every tumor cell is different and we want to understand which cells are the most aggressive ones, namely those that remain after chemotherapy and cause the tumor to relapse. We want to attack these cells specifically by identifying target molecules for treatment.
We are investigating this heterogeneity at various levels: At RNA level, we can identify the phenotype, i.e. the identity of a tumor cell. This shows whether it is more similar to a healthy cell or rather stem cell-like and thus more aggressive. Some cells stay dormant for a certain period of time, but are eventually reactivated. We want to know why.
Another approach is mass spectrometry at the single-cell level, which we use in particular to investigate the spatial heterogeneity of a tumor. The aim is to combine both methods and learn how the cell types in the tumor interact with each other. In this way, we hope to find prognostic markers that predict the course of the disease.
Why did you choose to become a scientist?
One of the first books I wanted to read was a book explaining sky and earth for children (“Mein erstes Buch von Himmel und Erde”). That was in first grade elementary school. Earth, sky and human beings were extremely exciting for me. I wanted to know what was going on in our world.
In secondary school I had my first contact with molecular genetics. I chose biology as my major subject, in which I also wrote a term paper.
And then you studied biology?
Originally, I studied mathematics and physics for a few semesters, then pharmacy and biology. However, it was particularly exciting for me to go into detail during my biology studies and learn about molecular mechanisms and how they interact in the body.
For my diploma thesis I worked in vaccine development at Intercell. After that, I was at the Institute of Immunology where I did my dissertation. However, I wanted to focus on medical science, to generate long-term benefits for patients.
During my dissertation, I had already cooperated with various groups of St. Anna Children's Cancer Research Institute. It is my dream job to work here because I find it incredibly important and great what people achieve here. It's fun to work in an environment of idealists who all have one common goal: to improve the lives of children with cancer.
What do you particularly like about your job?
Since my colleagues and I perform a lot of innovative diagnostics, we are regularly involved in the clinic's tumor boards. Together with clinicians, we discuss, for example, the genetic analyses of our lab. This enables us to offer a direct service to patients. In addition, I can contribute in my own way by doing research and developing new therapeutic concepts.
Where do you see particular challenges in childhood cancer research?
It is a balancing act. As a researcher, you quickly get excited about an idea and try to implement it. If you really want to make a difference, you have to cooperate with other people. Bringing many partners together for a joint project across Europe is fun and definitely a positive challenge. Nevertheless, it is also a learning process, because it is important to understand: What are the people´s needs to be able to work well together?
It can also be challenging when a hypothesis is not as confirmable as one might imagine. You dive into a project with a lot of optimism and then after months you realize that everything is much more complicated than you thought. Actually, it´s always more complicated than expected. However, at the moment we are on a very good path.
What does it take to be successful in science?
It is a very fulfilling task that leads to the experience of success again and again. Nevertheless, it can also be exhausting, you must stick to it, be persistent, keep at it.
Knowledge from other disciplines is also helpful. Although mathematics and physics were ultimately too theoretical for me, I still have an affinity for mathematics and technology. I therefore have a good understanding of the basic principles on which informatics is based on. This helps to work well together with other disciplines.
Are there times when you can switch off and not even think about your research?
I have a husband and two children. So there are moments when I don't think about research. However, in most cases I get up with work and go to sleep with work. This is not a stressful situation, as I enjoy doing it. Without being there with all one’s heart, it doesn't make sense. Science is not only my job, but an essential part of my life.
Sabine Taschner-Mandl, PhD
Sabine Taschner-Mandl, PhD, has been head of the Tumor Biology group at St. Anna Children's Cancer Research Institute since 2018, where she has been working scientifically since 2008. Taschner-Mandl completed her studies of biology at the University of Vienna with a diploma thesis in vaccine development at Intercell. This was followed by a PhD thesis and a post-doc position at the Institute of Immunology at the Medical University of Vienna. Besides her work at St. Anna Children's Cancer Research Institute, Taschner-Mandl was a visiting scientist at Significo and the University of Helsinki within the EC-FP7 Marie Curie Program.
For her research, Taschner-Mandl has received numerous grants, among others from the Austrian Research Promotion Agency, the Vienna Science, Research and Technology Fund and the ERA-NET initiative of the European Commission. The researcher is a member of international professional societies, such as the Advances in Neuroblastoma Research Association (ANRA) and the International Society of Pediatric Oncology Europe Neuroblastoma (SIOPEN), where she serves as co-chair of the Biology Speciality Committee. Taschner-Mandl's work has already been selected twice as Best Presentation at the annual SIOPEN meetings. She teaches at the Medical University of Vienna and is a reviewer for numerous scientific journals, including the Journal of Clinical Oncology and Nature Communications. The researcher's close international collaborations include the Princess Maxima Center in Utrecht, Charité University Medicine in Berlin and the Institut M. Curie in Paris.
Neuroblastoma is responsible for eleven percent of all childhood deaths caused by cancer. Although major international efforts have been made in recent years to develop new, improved therapies, e.g. immune therapies, the long-term survival of patients with metastatic high-risk disease is still very poor. For this group, the survival rate is less than 40 percent after initial therapy and less than ten percent after relapse.
Liquid biopsies reflect the exact course of the disease at any time during therapy and afterwards and therefore have the potential to revolutionize diagnostics and treatment of children with high-risk neuroblastoma. Since blood and bone marrow samples are less invasive than classical tumor biopsies, they are an excellent source of biomarkers for monitoring the course of the disease and as a basis for therapy decisions.
The LIQUIDHOPE consortium brings together international experts in the fields of biological and computer-based research in neuroblastoma with pediatric oncologists. Within this consortium, St. Anna Children's Cancer Research Institute aims at a rapid transfer of Liquid Biopsy procedures into clinical practice. It is planned to quantify tumor markers and immunotherapeutic target molecules on already scattered tumor cells in bone marrow samples using an automated microscopy system and to analyze DNA markers in blood and bone marrow using "digital droplet" PCR. These methods are supported by bioinformatic analyses based on the latest "deep-learning" algorithms and Software for visualization of complex multi-dimensional data. The specificity and sensitivity of the biomarker tests established by Taschner-Mandl and her group will be compared to those of the LIQUIDHOPE partners and then prospectively collected in the European-wide high-risk neuroblastoma study.
Press Release _ Childhood Cancer Awareness Month_Researcher Portrait Sabine Taschner-Mandl_StAnnaKinderkrebsforschung
Pressemitteilung _ Childhood Cancer Awareness Month_Forscher-Porträt Sabine Taschner-Mandl_StAnnaKinderkrebsforschung