From patient care to research: unveiling long-term outcome and treatment strategies
I am Julia Weisinger from Hungary. I studied medicine at Semmelweis University in Budapest and during my studies I got involved in the research of cell signaling in the innate immune system. After the university, I had a big decision to make: research or patient care? I chose the latter and became a hematologist and internist, but never really gave up on research. During my years of practice, I have actively participated in clinical trials as offering new and effective therapeutic options was always a priority at our department. My recent focus has shifted towards diseases that encompass both hematological and immunological features, like thrombotic thrombocytopenic purpura (TTP).
In the TOLERATE project I will be a PhD student at Sorbonne University in Paris. My research will focus on the clinical characteristics and long term consequences of TTP. As long term survival and treatment options preventing relapse are still not optimal, my work will focus on two main topics: the cardiovascular-cerebrovascular conditions and risk factors during long-term follow up, as well as the identification of optimal preemptive treatment modalities. The majority of my work will be performed on the CNR-MAT registry, which is the French national database for thrombotic microangiopathies, involving TTP patients from all over France. Additionally, my responsibilities entail laboratory-based investigations, where I will evaluate possible predictive biomarkers within this patient cohort.
As a result of my work we will get a more detailed picture on the long term survival of TTP. Based on these data, we would like to optimize preemptive treatment, move towards a more personalized approach and as a long term effect, implementing these results in everyday patient care will hopefully improve survival.
Being a part of this TOLERATE project offers a great opportunity for me to engage in research while upholding my clinical approach. Given the rarity of TTP, working in a specialized center provides great clinical experience. As I was always interested in innovative therapies, I am enthusiastic about being involved in various phases of drug development.
I have always believed that working abroad, joining international teams, and diving into the work of other centers brings incredible professional and personal experience that you just can"'"t get anywhere else. And it is just an extra that I get to live and work in one of the most beautiful cities in the world.
From Industry Insights to Laboratory Pursuits
My name is Sara and I come from a city next to Barcelona, Spain. I studied biotechnology in the Ramon Llull University (Barcelona) as I always showed interest in nature and its understanding. During my last year of the bachelor, I enrolled in an Erasmus in Grenoble INP university (Grenoble, France), from which I enjoyed the experience of moving abroad. After the bachelor, I did a more industry-oriented master degree in Pompeu Fabra University (Barcelona) that allowed me to work for two years in a biotechnological company. With this experience I learned about the translatability of science and basic research to the patient’s life. It was also through my work in the company that I entered the world of haemostasis and more precisely, I got to know about iTTP and all the unmet needs for the diagnosis and treatment of this condition. Also, with this experience I discovered that, despite the different possible paths one can take having a scientific background, I wanted to continue to work in a laboratory environment. In addition, I wanted to further develop myself as a researcher and improve my skills, bringing at the same time some new knowledge to the field. Therefore, I had the willing to do a PhD to be able to conduct my own and innovative research. Yet it was not possible in the company. It was through this search that I found the opportunity to apply to the TOLERATE project.
In the TOLERATE project nº 2, a new therapy for iTTP will be explored using universal chimeric antigen receptor (uniCAR) T cells. This technology is derived from the cutting-edge therapy of CAR T cells, to overcome its already described adverse effects. The aim of the project is to modify both mouse and patients T cells to direct them and deplete antigen-specific B cells. Therefore, eliminating only the B cells that are targeting the self-antigen and harming the patient’s homeostasis. The experiments will be performed in vitro and later in a mouse model. This same approach could be then translated to many other autoimmune diseases.
For all of this, I am glad of having this opportunity that allows me to take up the challenge of moving in a new country and being, at the same time, part of an international and intersectoral network. It also gives me the opportunity to meet a lot of different and interesting people, amongst them, 7 other DCs with whom I can share the experience. I am really motivated to carry out this project and I’m happy to have the challenge to develop a very innovative therapy, in a such interesting feel like iTTP and autoimmune diseases. With all this I hope to contribute, in one or other way, to improve the lives of some patients.
Bubbly Biotechnologist from Bombay!
My name is Rutuja, and I am a 26-year-old scientist from India. My scientific journey began in Mumbai, where I pursued my Bachelor's and Master's degrees in Biotechnology. During my studies, my fascination with immunology and immunotherapy took root, driving me to explore this field further.
I had the privilege of working as a Junior Research Fellow at the esteemed Indian Institute of Technology - Bombay (IIT-B), focusing on Phase-I clinical trials for anti-CD19 CAR T cells. This experience exposed me to clean room environments and scaled-up production pipelines in CAR-T cell technology.
Seeking to deepen my expertise, I embarked on a new adventure at the Microbiology, Immunology, and Hygiene Institute in Erlangen, Germany, where I collaborated with PD. Dr. Kilian Schober. Together, we worked on developing CRISPR screens in primary human T cells to understand the metabolic changes they undergo after activation. This journey enriched my understanding of T cell biology, both in physiological and metabolic aspects, allowing me to grasp their responses to external stimuli more profoundly.
Driven by my passion for translational and personalized medicine, I am now pursuing my Ph.D. with a focus on designing Reverse Chimeric Antigen Receptor (RevCAR) -T cells to treat immune TTP. This groundbreaking technology originates from the brilliant minds of my working group, led by Dr. Michael Bachmann at Helmholtz-Zentrum Dresden-Rossendorf (HZDR) in Dresden, Germany. The RevCAR-T cell platform is an adapter-based innovation that has already proven its efficacy in multiple cancer models. We now aim to employ this technology in targeting and clearing autoreactive B cells. By utilizing patient-derived T cells to engineer them into RevCAR-T cells, our goal is to achieve notable effects in patients and eventually scale up this therapy in personalized medicine.
I am excited about the potential of this resourceful technology to make a significant impact in the lives of patients and contribute to the advancement of personalized medicine.
Getting started in a big way!
Hello! My name is Maria del Mar Tolos Garcia, but I have always been Mar for my family and friends. I was born in Reus (Spain), a city 100 km south of Barcelona. Ever since I was a child, I got a passion for science. Over time, this interest focused on how diseases work and especially, how to develop therapies to treat them. For this reason, I decided to graduate in Biology and Biotechnology.
After five years of hard work, my passion did not decrease and so, I decided to continue with a master’s degree in Advanced Immunology. Shortly after I graduated, I was selected to join TOLERATE. Although I have little experience now, I am sure that I have enough perseverance and motivation for this project!
My project will consist of developing modified regulatory T cells (Tregs) that would help treat autoimmune diseases, with the autoimmune disease iTTP as a model. Tregs are part of the immune system, a system in our body that protects us from possible diseases. Their main function is to regulate the response of the other cells in the immune system to avoid a response toward our own body. If this occurs, the patient will develop what is known as an “autoimmune disease”, like iTTP.
Since these cells have been shown to be dysregulated in autoimmune diseases, and they offer the opportunity to target the cells that cause the disease, we thought we can use them to treat iTTP.
TOLERATE and this project are important, especially, for iTTP patients. This is because as with many rare diseases, there is either a lack of information, or patients have fewer or expensive treatments available. Therefore, TOLERATE can be a useful platform to raise awareness across Europe (and beyond!) about the disease, what it is like to live with it, and develop new therapies for it.
As a recent graduate, both TOLERATE and my project are important and challenging for me because of many reasons. It allows me to introduce myself to the international job-market, develop lab-related skills and familiarize myself with a more industrial approach to science. Also, I get the opportunity to move to another country, learn the language and get to know their culture. I am very sure that, all these opportunities and challenges will help me grow and mature a lot alongside the other seven doctoral students!
A Belgian biotechnologist’s dedication to Amster-damn good research
My name is Margot and I am from Belgium. My educational journey has revolved around the vibrant city of Leuven, where I have had the privilege of gaining valuable knowledge and experiences. It all began with my professional bachelor's degree in Biomedical Laboratory Technology at UCLL, which gave me hands-on lab experience and laid a solid foundation as laboratory technician. In the final year of my bachelor's program, I embarked on an exciting internship at Uppsala University (Sweden), which turned out to be the catalyst for my aspirations to pursue higher education. Motivated by the vast possibilities and intellectual stimulation offered by academia, I transferred to KU Leuven for a master’s program in Biochemistry and Biotechnology. During this program I interned at Virovet, a company that develops vaccines for livestock, and I joined the Neyts-lab of Virology, Antiviral Drug & Vaccine Research for my master's thesis, where I engaged in vaccine research. The intricacies of the immune system and the potential of vaccines for transformative medical breakthroughs captivated my mind and fueled my ambition to pursue a PhD in the field of immunology.
Although Leuven has been my academic soulmate, I am eager to embark on the next chapter of my scientific journey, to embrace new perspectives and shape a brighter and healthier future with my PhD research. The TOLERATE project and MSCA provide a unique package to launch my career as a researcher by allowing me to participate in relevant training modules, in exchanges with the industry and in public outreach activities. Furthermore, one of the biggest advantages of being part of a network is that you are part of a team. I have the privilege to collaborate and network with passionate researchers from diverse backgrounds, which will have a profound impact on my personal and professional growth.
My project at Sanquin (Amsterdam) will be focused on the development of novel therapies for iTTP to re-educate the immune system to recognize ADAMTS13 as a harmless protein, rather than a foreign invader to be attacked. I will do this by delivering ADAMTS13 to specific opportune destinations in the body to leverage on natural mechanisms of tolerance. My research aims to achieve more targeted immune intervention, preserving overall immune function, hence improving the quality of life of iTTP patients.
From Bologna to Barcelona with dedication, curiosity and a professional camera always around my neck
My name is Daniela Greco and I am from Italy. I have always been fascinated by both art and science. Indeed, I started my scientific career in 2014 at the University of Bologna, where I studied Biological Sciences while working as a wedding photographer in the free time. Since then, it has been an amazing rollercoaster ride that led me here to the TOLERATE Network.
During my bachelor, I developed a strong curiosity and interest in understanding the molecular basis of life at a fundamental level which convinced me to complete a master’s degree in Molecular and Cellular Biology. After covid, I decided to change and to challenge myself with new personal and professional experiences. I moved to Barcelona for an Erasmus+ Internship where I joined the Regeneration and Reprogramming Group led by Dr. Cosma. Here, I had the opportunity to work on setting up a novel cell therapy for human retina regeneration based on cell fusion. Meanwhile, it was life-changing to fully experience the vibrancy and internationality of the city, full of events and life. Afterwards, in 2021 I joined the Beta Cell Biology group at the San Raffaele Diabetes Research Institute in Milan where I was provided with a deeper insight into cell inflammation and diabetes under the supervision of Prof. Piemonti.
These experiences have been a game changer for me as I was really fascinated by the potential and importance of translation research to improve human health. For this reason, I applied for the MSCA PhD in the TOLERATE project where I was selected to join Ahead Therapeutics in Barcelona. In this project, I have the desire to bring my scientific contribution with creativity and curiosity.
During my PhD I will focus on developing a nanoparticle-mediated immunotherapy to re-establish self-tolerance in iTTP. The project aims to produce autoantigen-loaded phosphatydilserine-rich liposomes and validate their translational potential in inducing tolerogenic dendritic cells and expansion of regulatory T cells. I will assess iTTP PS-liposomes tolerogenity using samples from both control and iTTP patients and determine the therapeutic effects using iTTP mouse model.
I am deeply thrilled to join the TOLERATE Consortium. I strongly believe that being part of such an international and stimulating network will be one of the most enriching and constructive experience both personally and professionally.
Researcher in development
Hi, I am Timon from Germany. I have a bachelor’s and Master of Science in biotechnology and I am one of the PhD students in the MSCA TOLERATE program.
Even at school, the scientific world grabbed me, be it biology, chemistry or physics, but it was clear to me that only biology was right for me. I started my scientific pathway with a bachelor’s in biotechnology but I quickly noticed that it is inevitable for me to not go into medical research. Therefore I switched for my master’s to a university connected to a clinic, providing me with more engaging and interesting medical research. Despite the pandemic, I was able to participate in different courses on stem cell biology and immunology at the clinic. Especially my master’s thesis has shown me how much fun I have in research. The opportunity to form your project according to your ideas is an experience I will never forget and never want to miss again.
For my PhD, I have moved for the first time in my life abroad to Dublin. There I want to unravel the mechanism of how ADAMTS13 is removed from the blood. ADAMTS13 is an enzyme which is important for maintaining a balanced haemostasis. I will perform a range of experiments to determine which cell and receptor types are involved in the clearance mechanism. In the long term, I will also try to find the interacting parts of the receptors and ADAMTS13. With this new knowledge, I hope to be able to create a version of ADAMTS13 that is not cleared as fast and is even more tolerogenic. This project could potentially produce results which might, in the long run, be beneficial for the development of better therapeutic approaches for iTTP.
The project is embedded in the exciting MSC Actions. For me, it is an opportunity to strive for research in an incomparable way. In the first few months, I have met so many incredible researchers with whom I will also work together. It is an amazing concentration of knowledge and skill that will create the perfect foundation for my future as a medical researcher. Another benefit is that the program allows me to fully focus on my project while still being able to connect with my fiancé and my family despite the distance. Of course, moving abroad is always a challenge and it can be difficult to find your way around a new lab at first, but it is definitely worth it. In return, you get the opportunity to do state-of-the-art research, answer exciting scientific questions and work with people from all over the world.
From Stethoscope to Pipette: A Medical Doctor's Quest for Scientific Breakthroughs
My name is Andreea-Adela Icleanu, and I'm originally from Timișoara in Romania. I enjoyed the wonderful opportunity of completing my studies at University of Medicine and Pharmacy "Victor Babeș" in Timișoara, where I gained the information and abilities I needed to start my career as a medical professional. After finishing my studies, I had the chance to work for two years as a medical doctor (M.D.) at the "Louis Turcanu" Hospital for Children. I developed a growing interest in immunology during my training as a physician and I started gaining practical knowledge in the complex area of thrombotic microangiopathies. After personally experiencing the impact of these conditions, I came to understand the crucial role that commitment and compassion play in enabling the improvement of others' lives.
I'm currently Doctoral Candidate 8 in the TOLERATE Programme, and I find myself embarking on an exciting new chapter in my career. I am working in Semmelweis University's Department of Internal Medicine and Hematology in Budapest, Hungary. My main goal is to understand the complex immunological processes while I monitor patients with immune-mediated thrombotic thrombocytopenic purpura over an extended period of time. The objective of my research is to identify the factors that are leading to the loss of Tolerance to the protease named ADAMTS13 which leads to the generation of anti-ADAMTS13 antibodies and the development of new acute episodes of iTTP. This information can be used to make an earlier diagnosis, allowing for more effective prevention of iTTP episodes by treating appropriately selected individuals at the right time during follow-up.
The enthusiasm I feel toward this project is both professional and personal. Its significance resonates deeply with me, as it seeks to bring about essential improvements within the medical system, specifically for patients suffering from immune-mediated thrombotic thrombocytopenic purpura (TTP). By improving their care and preventing further acute episodes of iTTP, I hope to contribute to their well-being and create a significant change in their lives. I am really excited about expanding my medical knowledge and competence during this doctoral programme, by achieving valuable clinical and laboratory experience while making me a part of the long-term solution.