Awards

The year of Daniele Tauriello

Big ambitions with miniature tumor models

Last year, Daniele Tauriello was awarded an NWO/ZonMW Vidi grant as well as Radboudumc’s Hypatia grant for research group leaders. These grants have allowed him to start an independent group. Now, he can continue his research into restoring the immune system to prevent cancer from spreading.

Can you tell us a bit about the research you’re doing at RIMLS? I believe, it’s related to the postdoc research you did in Barcelona.
“In 2011, I began investigating colorectal cancer (CRC) metastasis at the Institute for Research in Biomedicine (IRB Barcelona). The aim was to generate a better model, with an intact immune system. My colleagues and I created a metastatic mouse model that recapitulated just about all the relevant characteristics of human CRC with poor prognosis. I then put the tumors generated by our new model into culture as organoids."
 
“Successful reimplantation (in mice) of those organoids was vital in the development of new insights on immune suppression in liver metastasis, leading to a promising new treatment option. The future, I think, lies not in merely killing the cancer cells directly, but rather in treating the whole tumor ecosystem."
 
“So, with the mouse tumor organoids I generated in Barcelona, I now want to look at an earlier point in time in metastasis—when these lesions are still undetectable and, presumably, either biding their time or struggling to grow out. We’ll model the tumor microenvironment of these early lesions in cell culture conditions.
 
“Next, we'll make patient-specific in vitro models to gain more understanding of the cell-to-cell communication responsible for immune evasion and tumor metastasis. At least in principle, we could then develop and test bespoke therapies for a given patient. The idea is that if we can stop the tumor early, we can prevent metastatic outgrowth, which, of course, is better than having to cure it.”
 
Why conduct this research at Radboudumc? Were you confident that you would be able to secure grants by associating with RIMLS?
“For personal reasons, I wanted to come back to the Netherlands. More than any other institute I considered, I found both a strong match of scientific interests and facilities and a supportive atmosphere. The new rules for the Vidi grant mean that before you can apply, you need an embedding guarantee from a Dutch institution where you intend to conduct your research. With the help and support of researchers at the departments of cell biology and tumor immunology, I was able to write my proposal and secure the grant."
 
“As for the Hypatia grant: I believe I owe this opportunity in part to the same supportive researchers, lobbying on my behalf. I’m very grateful for this. Getting both grants gives me the means to provide an income for myself and a team of researchers to work on this ambitious project and develop other clinically-oriented projects as well.”
 
You’ve now been in Nijmegen for several months. Are you satisfied with your choice to come work at RIMLS?
“Yes, definitely. Very early on, I met Henk Verheul – professor in medical oncology ­– who moved to Nijmegen the same time I did. Although we work in different departments, we discovered that our research is highly complementary. I concentrate in the pre-clinical setting with translational ambitions, and he works in the clinic, in need of more fundamental research partners. It's great to bounce ideas off each other and collaborate.
 
“I also started a translational CRC research alliance together with Nielka van Erp – associate professor at the pharmacy department – and Iris Nagtegaal – professor of gastrointestinal pathology – to address urgent clinical problems and bring novel therapies to patients."
 
“But that’s not all. There's also Annemarie Boleij from the pathology department with whom I’ll study the role of microorganisms in metastasis. And with associate professor in translational immunohematology, Harry Dolstra, we're already studying a new immunotherapeutic option for patients with metastasis. And I've not even mentioned the collaborations within the departments of cell biology, tumor immunology, and other RIMLS groups. The open and positive atmosphere at the institute is exceptional and has made my start both pleasant and exciting."
 
What are your ambitions for your research and your career?
“I want my research to impact the lives of people with cancer. The hope is not only to prolong the lives of patients but also to prevent metastatic suffering, and reduce treatment toxicity. It may sound very ambitious, but I’ve three reasons to be optimistic: an increasingly effective handle on cancer drivers, an upsurge in the field of immuno-oncology, and the emerging insight of the tumor ecosystem to guide treatment combinations."
 
“I started by carefully setting up a team for my lab. I think it's crucial to find qualified candidates that not only complement one another but also work well together. As group leader, I'm responsible for the team: their growth as researchers as well as the collective atmosphere. I need researchers who can work independently on problems that will later come together in solving more complex puzzles. Good science requires people with expertise who are willing to share their pragmatic creativity."
 
“I feel confident I have the ingredients to build an outstanding research line."
 
Daniele Tauriello was one of three researchers at RIMLS who was awarded a Vidi grant in 2019. Who are the other Vidi awardees, and what research are they doing? 
Mathijs Jore works at the Department of Medical Microbiology, and his research focuses on malaria. His fundamental research looks at how malaria parasites can evade the human immune system at a molecular level. The aim is that the acquired insights will be used to develop novel drugs and vaccines against malaria.
 
Johannes Textor is looking into how intelligent our immune system is, at the department of Tumor Immunology. He will train computer models of the immune system to recognize text and images to understand how the system learns, forgets, and gets confused. This will help to design therapies that use the immune system, such as vaccines.
 

Five NWO Veni grants being awarded to RIMLS researchers

Can’t remember ever being as nervous as I was for my Veni defense

With five NWO Veni grants being awarded to RIMLS this year, the institute was generously rewarded. Four Veni awardees came together to discuss their research, their Veni grants, and their research careers.

Who are this year’s 250 kEuro Veni awardees, and what are they researching?
Rob Aarts is the only Veni awardee this year who works part-time in the clinic as an internist in training. His research focuses on the memory of the innate immune system and the role of the anti-inflammatory cytokines interleukin-37 and IL-38.
 
Jitske Jansen was awarded the Veni grant to study kidney regeneration after acute kidney failure. Her aim is to elucidate molecules secreted by immune cells and pericytes that are essential for successful for kidney epithelial repair.
 
Martijn van den Bosch focuses on osteoarthritis and aims to unravel the inflammatory mechanisms that drive the osteoarthritis pathology, which might be used to develop disease-modifying therapies.
 
Annie Yang is looking into the complex life cycle of parasites in hepatocytes during malaria infection. Back in Melbourne, she had already begun researching the liver stage of the malaria parasite. She moved to Nijmegen because of Radboudumc’s strong history in malaria research, especially in terms of innovation.
 
Anat Akiva also obtained a Veni grant. She was working in Eindhoven and brought the grant with her when she transferred to Radboudumc. Her research focuses on biomineralization, aiming to understand the processes of hard tissue formation in health and disease.
 
Were you confident the committee would award you the grant? 
Jitske: “I can’t remember ever being as nervous as I was for the Veni defense. It was basically a go or no-go for my research career. It was the final time I was permitted to apply, considering the time constraints of application – no more than three years after completing your PhD. I needed the money to be able to continue in research, which I'm passionate about. The Veni will pay for my income in the coming years, but I'll need more financing to be able to achieve everything I want with my research.”
 
Rob: “I also had my medical career and other grant applications if I didn’t get the Veni, so not super nervous. Of course, getting a personal grant is so much nicer and gives you more freedom. I want to combine the clinic and research. Attaining a Veni grant is a significant first step to becoming a researcher.”
 
Annie: “I was surprisingly relaxed for my defense. I knew someone else from my department (Medical Microbiology) was also applying. The chance of both of us getting a Veni grant was very slim. I, therefore, lowered my expectations and also concentrated on getting other grants. It was also nice that I saw my mentor just before I went in. She gave me a word of encouragement, which calmed me down.”
 
Martijn: "For me, it was the second time applying for the Veni grant, and, like Jitske, it was my last chance to get it. However, as I’d done a defense the year before, I knew what to expect. I was more nervous the first time. Whereas the first time the questions sometimes took me by surprise, I was now totally prepared.”  
 
Do you have tips for PhD candidates considering a career in research?
Martijn: "Choose a topic that truly interests you. No grant application is easy. There are multiple rounds, and I'm sure that if you're not motivated enough, the committee will soon filter you out. It would help if you also took a chance with your topic. Remember: mid-risk means mid-gain."
 
Annie: “I noticed that the difference between criteria in Australia and Europe is that here they’re looking for more out-of-the-box ideas. In Australia, you almost have to have proven your hypothesis before you get funding. I found my research topic because I kept waiting for someone else to solve an issue that stagnated my research. I scanned all the literature, but the answer never came. So, I decided to solve the problem myself.”
 
Jiske: “Start with the patient. How could you solve a particular problem they face? It might also be useful to look at the 'front end.' For example: successfully regenerating the kidney after acute renal failure might possibly prevent the progression to end-stage renal disease and the need for dialysis treatment. Also, start writing your proposal on time!"
 
Rob: “My research is fundamental, yet as it has to do with the immune memory system, it's also applicable to many diseases. That may have helped to get the grant. I think it also helps if your research is a logical next step after your PhD research. That you have the necessary background." 
 
How was the support from RIMLS in trying to attain these national grants?
Rob: “I believe the success rate of awarded Veni-Vidi-Vici grants is a bit higher for Radboudumc than other medical centers.”
 
Martijn: “I heard that too. I think their pre-selection has a lot to do with it. We have to hand in our proposals to Radboudumc’s Grant Support Office in May. It makes you think about your research a lot.”
 
Annie: "They expect you to come up with something novel. There are several rounds, discussing your ideas back and forth. The process forces you to think about things, giving you enough time to work out your topic.”
 
Jitske: “They also help prepare you for what’s to come during the grant application: writing proposals, rebuttals, and interview training.”
 
Martijn: “It also helps that many PI’s at Radboudumc have also gone through the Veni-Vidi-Vici review process. They know from experience what questions could come up and can help prepare you through mock interviews." 
 
Annie: “RIMLS’s orientation is horizontal. Supervisors include you in their grant applications for bigger projects. You have brainstorm sessions together, and they send grant proposals to everyone on their team for feedback. It teaches you things for your own grant proposals."
 
Rob: "You're truly part of a team here. And you can ask help from anyone, whether it's another PhD candidate also applying, or a technician or a PI. Everyone is committed to research."