Ion Cristian Cirstea - Team Leader of Ulm University

Get to know Ion Cristian Cirstea, Team Leader at Ulm University, whose work bridges biochemistry, genetic engineering, and the study of RAS signalling in both RASopathies and cancer. In this interview, he shares what inspired him to join EURAS, his role in uncovering new disease mechanisms and therapeutic possibilities, and how patient communities continue to shape and motivate his research. Dive in to explore how insights across related diseases can open new paths toward better treatments.

Can you please provide a little background on yourself: What is your field of research, how long have you been in this field
I studied biochemistry at the University of Bucharest (Romania) and I did a PhD in genetic engineering at the Max Planck Institute of Molecular Physiology Dortmund (Germany). When I started my postdoctoral time in 2007, I worked on the functional characterization of RAS mutations in RASopathies, and on dysregulated signalling pathways in RAS cancers and further developed as a cell biologist. After establishing my research group in 2012, I continued my studies on RAS GTPases in cancer and RASopathies with the overall aim to identify novel regulatory mechanisms and biological processes that may be used for new therapeutical approaches.

Why did you want to join the EURAS project?
First of all, I joined the EURAS project because I greatly admired this initiative driven by patients’ parents and it gives me the chance to hopefully contribute to the wellbeing of RASopathy and SYNGAP1 patients, respectively. Second, it gave this unique opportunity to work with scientists across the EU and with different scientific specialities, to learn from new and different things other than my research and improve my scientific skills.

What is your role in the EURAS project and what are your main responsibilities?
I am involved in the characterisation of novel research models used in the project. In addition, I am part of the identification of common and divergent disease signatures in Costello (CS), cardio-facio-cutaneous (CFC) and SYNGAP1 syndromes that can be used for either assessing the success of our selected treatment strategies or can become a starting point for subsequent novel therapeutical approaches. I am also Task 4.5 leader which focuses on cellular signalling processes in cellular and animal models.

What are your ambitions for the project?
My ambition would be to identify therapeutical approaches that improve neurodevelopmental phenotype and also hopefully provide additional signalling processes that could lead to more appropriate therapies.

What has been driving your passion and motivation for medicine, research and involvement with patient organisations?
My initial driving force was curiosity on how cells function, how cellular proteins interact with each other and how these interactions regulate cellular activities. Later, meeting affected children and their families as I started my research on RASopathies fuelled my drive even more to discover the molecular bases of RASopathy diseases.

How can existing knowledge on other and related diseases help in understanding RASopathies?
The research we conduct on RAS oncogenes in cancer and on RASopathies is very complementary in leading to better and more targeted understanding of both. The impact of RAS mutations on cellular signaling and homeostasis in RASopathy is considered to be milder when compared to cancer mutations and, at the moment, it is widely accepted that some signaling pathways are affected in both. Research performed on RAS cancers in the last decades has led to the creation of numerous libraries of therapeutical molecules. Although most therapeutic molecules have failed in cancer treatment, we cannot exclude that they could be useful in treating RASopathy pathologies. The concept of drug repurposing in RASopathy has thus become very appealing based upon this research on RAS cancers. On the other side, when looking from a RASopathy research point of view and what can be learned for RAS cancers, our unpublished data on CS mouse models indicates that this syndrome is associated with metabolic wasting syndrome. This data may be important for RAS cancers where metabolic wasting syndrome (cancer cachexia) is extremely detrimental to cancer patients’ wellbeing. Our research on the CS mouse model has further revealed that HRAS mutations that trigger only a moderate activation, also trigger bone loss by increasing the number of bone resorbing cells (osteoclasts), which provides a potential mechanism that may be studied in the case of age-related bone loss. Altogether, this indicates that our work in both diseases provides benefits in both research directions and can lead to more targeted research and potential successful therapies.